Materiały źródłowe

• #1 Common Variable Immunodeficiency: Epidemiology, Pathogenesis, Clinical Manifestations, Diagnosis, Classification, and Management – PubMed

  https://pubmed.ncbi.nlm.nih.gov/30741636/

  Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by hypogammaglobulinemia and increased susceptibility to recurrent bacterial infections. […] Numerous studies have demonstrated that immunological and genetic defects are involved in the pathogenesis of CVID. […] However, in most cases, the genetic background of the disease remains unidentified.

• #2 Common variable immune deficiency (CVID) | Immune Deficiency Foundation

  https://primaryimmune.org/understanding-primary-immunodeficiency/types-of-pi/common-variable-immune-deficiency-cvid

  Common variable immune deficiency (CVID), previously known as adult-onset hypogammaglobulinemia, is one of the most frequently diagnosed primary immunodeficiencies. It is characterized by low levels of serum antibodies, which cause an increased susceptibility to infection. […] An additional characteristic is a decreased IgA and/or IgM level, or a low level of all three major types of immunoglobulins (IgG, IgA, and IgM). In some individuals, there are defects of the T cells, and this may also contribute to increased susceptibility to infections as well as autoimmunity, granulomatous disease, and cancer. […] Although people with CVID have depressed antibody responses and low levels of immunoglobulins in their blood, some of the antibodies they produce may attack their own tissues (autoantibodies).

• #3 Common Variable Immunodeficiency – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549787/

  Common variable immunodeficiency is a disorder characterized by defective B cell function leading to impaired immunoglobulin production. […] While some researchers have identified some genetic defect, the fundamental cause of CVID has been challenging to determine. […] The main cause of CVID remains unknown despite more than four decades of investigation. It is known that environmental and genetic factors may be involved: approximately, 20% of CVID patients have a first-degree family member with a selective IgA deficiency; while the specific environmental factors are unclear, the genetic influence in CVID is believed to cause an intrinsic B cell defect (CD19-deficiency by mutations in CD19; 16p11.2), an intrinsic T cell defect (ICOS-deficiency by mutations in ICOS; 2q33), and mutations in TNF receptors (TACI-deficiency or BAFFR- deficiency by mutations in TNFRSF13B and TNFRSF13C respectively; 17p11.2 and 22q13.1-q13.31).

• #4 Pathogenesis of common variable immunodeficiency – UpToDate

  https://www.uptodate.com/contents/pathogenesis-of-common-variable-immunodeficiency

  Pathogenesis of common variable immunodeficiency […] Common variable immunodeficiency (CVID) is a heterogeneous immune disorder characterized by recurrent sinopulmonary infections, autoimmune disorders, lymphocytic and/or granulomatous infiltrates, and an enhanced risk of malignancy. […] CVID is defined by the following: […] Markedly reduced serum concentrations of immunoglobulin G (IgG), in combination with low levels of immunoglobulin A (IgA) and/or immunoglobulin M (IgM) […] Poor or absent antibody response to infection or immunization or both […] An absence of any other defined immunodeficiency state.

• #5 Common Variable Immunodeficiency – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549787/

  The clinical variability of CVID suggests that multiple immunoregulatory defects can result in the final common pathway of hypogammaglobulinemia. […] Reports exist of numerous immune-system abnormalities, the most common of which is defective antibody formation. […] The number of B cells is normal in the majority of patients, but many of them have reduced percentages of isotype-switched memory B cells capable of producing immunoglobin isotypes that are critical toward antibody response recall. […] B cell maturation is defective, and the action of toll-like receptors 7 and 9 (TLR7 and TLR9) becomes impaired because of a yet unknown mechanism. […] Determining the number of isotype-switched memory B cells is of utmost interest because it provides information about the immaturity of the B cell, relates to the numbers of plasma cells in the bone marrow, and gives information about the possible clinical outcomes.

• #6 Common variable immunodeficiency – an update | Arthritis Research & Therapy | Full Text

  https://arthritis-research.biomedcentral.com/articles/10.1186/ar4032

  Common variable immunodeficiency (CVID) describes a heterogeneous subset of hypogammaglobulinemias of unknown etiology. […] Informative monogenetic defects have been found in single patients and families but in most cases the pathogenesis is still elusive. Numerous immunological studies have demonstrated phenotypic and functional abnormalities of T cells, B cells and antigen-presenting cells. A hallmark is the impaired memory B-cell formation that has been taken advantage of for classifying CVID patients. […] The immune system of CVID patients has been investigated by many studies, describing both phenotypic and functional abnormalities in the adaptive and, more recently, also in the innate immune system. However, the plethora of these defects, their unequal distribution within different CVID cohorts and the lack of a real comprehensive and combined analysis of all of them have so far precluded a definitive mapping of all immunopathogenic pathways leading to CVID.

• #7 Common variable immunodeficiency – Wikipedia

  https://en.wikipedia.org/wiki/Common_variable_immunodeficiency

  Common variable immunodeficiency (CVID) is an inborn immune disorder characterized by recurrent infections and low antibody levels, specifically in immunoglobulin (Ig) types IgG, IgM, and IgA. […] The causative factors of CVID are not fully known. Genetic mutations can be identified as the cause of disease in about 10% of people, while familial inheritance accounts for 10-25% of cases. Rather than arising from a single genetic mutation, CVID seems to result from a variety of mutations that all contribute to a failure in antibody production. […] Mutations in the genes encoding ICOS, TACI, CD19, CD20, CD21, CD80, and BAFFR have been identified as causative of CVID. […] The majority of CVID patients have normal B cell counts, suggesting the impaired antibody production is mainly a defect in the differentiation process of B cells into memory and plasma cells.

• #8 Common variable immune deficiency: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/common-variable-immune-deficiency/

  Common variable immune deficiency (CVID) is a disorder that impairs the immune system. […] The cause in CVID is unknown in approximately 90 percent of cases. It is likely that this condition is caused by both environmental and genetic factors. […] The genetic influences in CVID are believed to be mutations in genes that are involved in the development and function of immune system cells called B cells. […] Mutations in the genes associated with CVID result in dysfunctional B cells that cannot make sufficient amounts of antibodies. […] In about 10 percent of cases, a genetic cause for CVID is known. Mutations in at least 13 genes have been associated with CVID. […] The protein produced from this gene plays a role in the survival and maturation of B cells and in the production of antibodies.

• #9 Common Variable Immunodeficiency (CVID): Cause & Treatment

  https://my.clevelandclinic.org/health/diseases/21143-common-variable-immunodeficiency-cvid

  Common variable immunodeficiency (CVID) is a group of genetic disorders that affect your immune system. People with CVID have low levels of antibodies (proteins that fight infections) in their blood. […] Genetic variations (changes in your DNA, the instructions that make your body work) cause CVID. No single change causes CVID many different gene changes are associated with it and experts think it takes more than one change to cause CVID. The most commonly found mutations are in the TNFRSF13B gene. […] These changes mean that your B-cells a type of immune cell dont work properly. They dont develop into plasma and memory B-cells, which make antibodies (also called immunoglobulins). Specifically, people with CVID have low levels of IgG, IgA and IgM antibodies. […] The gene variations that lead to CVID are inherited in about 10% of cases. Experts dont know what causes them in the other 90% of people with CVID. They think epigenetic changes (changes in the way your body interprets DNA, caused by environmental or lifestyle factors) could contribute to developing CVID. But researchers need more studies to understand this theory better.

• #10 Common Variable Immunodeficiency – Page 3 of 7 – The Rheumatologist

  https://www.the-rheumatologist.org/article/common-variable-immunodeficiency/3/?singlepage=1

  ICOS is expressed on activated T cells and is of critical importance for correct T cell-B cell cooperation during the adaptive immune response. […] TACI directs immunoglobulin class switch recombination and negatively regulates B cell homeostasis. […] CD19 forms a receptor complex with CD21 (CR2), CD81, and CD225 (Leu13), which is referred to as the CD19-complex. This signaling complex fine-tunes and amplifies B cell receptor (BCR) signals after antigen binding. […] BAFF-R deficiency presents with a distinct immunological phenotype which had been inferred by BAFF-R-deficient mouse models: peripheral B cell numbers are low, transitional B cell numbers are proportionally increased, and IgA production is intact.

• #11 Common Variable Immunodeficiency – Page 6 of 7 – The Rheumatologist

  https://www.the-rheumatologist.org/article/common-variable-immunodeficiency/6/?singlepage=1

  Candidate loci for CVID have now been demonstrated at the HLA region on chromosome 6, chromosome 4q, and chromosome 16q. This genetic heterogeneity which probably mirrors the variable clinical presentation of this disease is further increased by the recent discovery of four candidate genes which were found to be mutated in CVID independently of the results of previous linkage and association studies. […] ICOS (inducible costimulator on activated T cells) was the first gene defect described in patients with CVID and has so far been described in nine individuals from four families, all of whom inherited the same mutation from a common founder. […] TACI deficiency was the second molecular genetic defect found in patients with CVID. […] CD19 deficiency is a very rare cause of CVID and, up to now, has only been described in four patients worldwide. […] My colleagues and I were able to identify two cases of homozygous BAFFR deficiency in one single kindred. […] The discovery of additional genes associated with CVID and the mechanisms by which the mutation promotes CVID will be essential for the future diagnosis and treatment of this disease.

• #12 Common Variable Immunodeficiency – Page 3 of 7 – The Rheumatologist

  https://www.the-rheumatologist.org/article/common-variable-immunodeficiency/3/?singlepage=1

  ICOS is expressed on activated T cells and is of critical importance for correct T cell-B cell cooperation during the adaptive immune response. […] TACI directs immunoglobulin class switch recombination and negatively regulates B cell homeostasis. […] CD19 forms a receptor complex with CD21 (CR2), CD81, and CD225 (Leu13), which is referred to as the CD19-complex. This signaling complex fine-tunes and amplifies B cell receptor (BCR) signals after antigen binding. […] BAFF-R deficiency presents with a distinct immunological phenotype which had been inferred by BAFF-R-deficient mouse models: peripheral B cell numbers are low, transitional B cell numbers are proportionally increased, and IgA production is intact.

• #13 Common Variable Immunodeficiency: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1051103-overview

  TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) mediates isotype switching in B cells. One series found that 4 of 19 unrelated individuals with CVID and 1 of 16 individuals with IgA deficiency had a missense mutation in 1 allele of TNFRSF13B (encoding TACI). TTACI mutations can result in CVID and IgA deficiency. Four genes have been documented to be mutated in CVID patients: ICOS, TNFRSF13B (encoding TACI), TNFRSF13C (encoding BAFF-R) and CD19. Heterozygous mutations in TNFRSF13B are also associated with CVID, whereas the other 3 genes are recessive. Those with a mutation in the TNFRSF13B gene may require further investigation. […] Autosomal dominant CVID has been linked to chromosome 4q. One study supports the existence of a disease-causing gene for autosomal dominant CVID/IgA deficiency on chromosome 4q. Other possible loci for dominant CVID genes are on chromosomes 5p and 16q.

• #14 Common Variable Immunodeficiency – Page 3 of 7 – The Rheumatologist

  https://www.the-rheumatologist.org/article/common-variable-immunodeficiency/3/?singlepage=1

  ICOS is expressed on activated T cells and is of critical importance for correct T cell-B cell cooperation during the adaptive immune response. […] TACI directs immunoglobulin class switch recombination and negatively regulates B cell homeostasis. […] CD19 forms a receptor complex with CD21 (CR2), CD81, and CD225 (Leu13), which is referred to as the CD19-complex. This signaling complex fine-tunes and amplifies B cell receptor (BCR) signals after antigen binding. […] BAFF-R deficiency presents with a distinct immunological phenotype which had been inferred by BAFF-R-deficient mouse models: peripheral B cell numbers are low, transitional B cell numbers are proportionally increased, and IgA production is intact.

• #15 Common Variable Immunodeficiency – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549787/

  Common variable immunodeficiency is a disorder characterized by defective B cell function leading to impaired immunoglobulin production. […] While some researchers have identified some genetic defect, the fundamental cause of CVID has been challenging to determine. […] The main cause of CVID remains unknown despite more than four decades of investigation. It is known that environmental and genetic factors may be involved: approximately, 20% of CVID patients have a first-degree family member with a selective IgA deficiency; while the specific environmental factors are unclear, the genetic influence in CVID is believed to cause an intrinsic B cell defect (CD19-deficiency by mutations in CD19; 16p11.2), an intrinsic T cell defect (ICOS-deficiency by mutations in ICOS; 2q33), and mutations in TNF receptors (TACI-deficiency or BAFFR- deficiency by mutations in TNFRSF13B and TNFRSF13C respectively; 17p11.2 and 22q13.1-q13.31).

• #16 Common Variable Immunodeficiency – Page 3 of 7 – The Rheumatologist

  https://www.the-rheumatologist.org/article/common-variable-immunodeficiency/3/?singlepage=1

  ICOS is expressed on activated T cells and is of critical importance for correct T cell-B cell cooperation during the adaptive immune response. […] TACI directs immunoglobulin class switch recombination and negatively regulates B cell homeostasis. […] CD19 forms a receptor complex with CD21 (CR2), CD81, and CD225 (Leu13), which is referred to as the CD19-complex. This signaling complex fine-tunes and amplifies B cell receptor (BCR) signals after antigen binding. […] BAFF-R deficiency presents with a distinct immunological phenotype which had been inferred by BAFF-R-deficient mouse models: peripheral B cell numbers are low, transitional B cell numbers are proportionally increased, and IgA production is intact.

• #17 Common Variable Immunodeficiency: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1051103-overview

  TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) mediates isotype switching in B cells. One series found that 4 of 19 unrelated individuals with CVID and 1 of 16 individuals with IgA deficiency had a missense mutation in 1 allele of TNFRSF13B (encoding TACI). TTACI mutations can result in CVID and IgA deficiency. Four genes have been documented to be mutated in CVID patients: ICOS, TNFRSF13B (encoding TACI), TNFRSF13C (encoding BAFF-R) and CD19. Heterozygous mutations in TNFRSF13B are also associated with CVID, whereas the other 3 genes are recessive. Those with a mutation in the TNFRSF13B gene may require further investigation. […] Autosomal dominant CVID has been linked to chromosome 4q. One study supports the existence of a disease-causing gene for autosomal dominant CVID/IgA deficiency on chromosome 4q. Other possible loci for dominant CVID genes are on chromosomes 5p and 16q.

• #18 Common variable immunodeficiency – Wikipedia

  https://en.wikipedia.org/wiki/Common_variable_immunodeficiency

  Common variable immunodeficiency (CVID) is an inborn immune disorder characterized by recurrent infections and low antibody levels, specifically in immunoglobulin (Ig) types IgG, IgM, and IgA. […] The causative factors of CVID are not fully known. Genetic mutations can be identified as the cause of disease in about 10% of people, while familial inheritance accounts for 10-25% of cases. Rather than arising from a single genetic mutation, CVID seems to result from a variety of mutations that all contribute to a failure in antibody production. […] Mutations in the genes encoding ICOS, TACI, CD19, CD20, CD21, CD80, and BAFFR have been identified as causative of CVID. […] The majority of CVID patients have normal B cell counts, suggesting the impaired antibody production is mainly a defect in the differentiation process of B cells into memory and plasma cells.

• #19 The Scope and Impact of Viral Infections in Common Variable Immunodeficiency (CVID) and CVID-like Disorders: A Literature Review

  https://www.mdpi.com/2077-0383/13/6/1717

  Due to its wide heterogeneity, there are increasing efforts to classify CVID cases into clinical subgroups as determined by the immunophenotypic profile. […] Investigations into the CVID+ phenotype have suggested commensal bacteria and microbial translocation could be driving a state of immune activation, contributing to inflammatory and autoimmune complications. […] Proposed carcinogenetic drivers for this phenomena can be split into cell-intrinsic mechanisms, where dysregulated cellular homeostasis, function or cell-to-cell interaction drives cancerous change; and cell-extrinsic mechanisms, where inadequate immune responses allow chronic infection (e.g., oncoviruses), deficient tumour surveillance or dysbiosis, predisposing to malignancy. […] Certain monogenic causes of the CVID phenotype, such as those affecting NFKB1, NFKB2, TNFSF12 (TWEAK), TNFRSF13B (TACI) and IKZF1 (IKAROS), have been individually reported with pronounced viral illnesses.

• #20 Common Variable Immunodeficiency – Page 3 of 7 – The Rheumatologist

  https://www.the-rheumatologist.org/article/common-variable-immunodeficiency/3/?singlepage=1

  Several groups have now demonstrated that the formation of memory B cells is severely impaired in the majority of CVID patients and leads to a concomitant depletion of long-lived plasma cells and a drop of serum Ig levels. The altered distribution of B cell subsets observed in CVID patients is now applied in disease classification. […] It has long been known that CVID also has a genetic component. While most cases of this disease occur sporadically, in 10% to 20% of CVID cases, at least one additional family member either suffers from CVID or selective IgA deficiency. Genetic linkage studies have revealed that the genetic defect involved in this disease cannot be reduced to a single gene locus. […] Candidate loci for CVID have now been demonstrated at the HLA region on chromosome 6, chromosome 4q, and chromosome 16q. This genetic heterogeneity which probably mirrors the variable clinical presentation of this disease is further increased by the recent discovery of four candidate genes which were found to be mutated in CVID independently of the results of previous linkage and association studies. These genes ICOS, TACI, CD19, and BAFFR encode for cell surface receptors on lymphocytes that play crucial roles either in peripheral B cell development or in B cell function.

• #21 Common Variable Immunodeficiency – Page 6 of 7 – The Rheumatologist

  https://www.the-rheumatologist.org/article/common-variable-immunodeficiency/6/?singlepage=1

  Candidate loci for CVID have now been demonstrated at the HLA region on chromosome 6, chromosome 4q, and chromosome 16q. This genetic heterogeneity which probably mirrors the variable clinical presentation of this disease is further increased by the recent discovery of four candidate genes which were found to be mutated in CVID independently of the results of previous linkage and association studies. […] ICOS (inducible costimulator on activated T cells) was the first gene defect described in patients with CVID and has so far been described in nine individuals from four families, all of whom inherited the same mutation from a common founder. […] TACI deficiency was the second molecular genetic defect found in patients with CVID. […] CD19 deficiency is a very rare cause of CVID and, up to now, has only been described in four patients worldwide. […] My colleagues and I were able to identify two cases of homozygous BAFFR deficiency in one single kindred. […] The discovery of additional genes associated with CVID and the mechanisms by which the mutation promotes CVID will be essential for the future diagnosis and treatment of this disease.

• #22 Common Variable Immunodeficiency: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1051103-overview

  TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) mediates isotype switching in B cells. One series found that 4 of 19 unrelated individuals with CVID and 1 of 16 individuals with IgA deficiency had a missense mutation in 1 allele of TNFRSF13B (encoding TACI). TTACI mutations can result in CVID and IgA deficiency. Four genes have been documented to be mutated in CVID patients: ICOS, TNFRSF13B (encoding TACI), TNFRSF13C (encoding BAFF-R) and CD19. Heterozygous mutations in TNFRSF13B are also associated with CVID, whereas the other 3 genes are recessive. Those with a mutation in the TNFRSF13B gene may require further investigation. […] Autosomal dominant CVID has been linked to chromosome 4q. One study supports the existence of a disease-causing gene for autosomal dominant CVID/IgA deficiency on chromosome 4q. Other possible loci for dominant CVID genes are on chromosomes 5p and 16q.

• #23 Common Variable Immunodeficiency: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1051103-overview

  TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) mediates isotype switching in B cells. One series found that 4 of 19 unrelated individuals with CVID and 1 of 16 individuals with IgA deficiency had a missense mutation in 1 allele of TNFRSF13B (encoding TACI). TTACI mutations can result in CVID and IgA deficiency. Four genes have been documented to be mutated in CVID patients: ICOS, TNFRSF13B (encoding TACI), TNFRSF13C (encoding BAFF-R) and CD19. Heterozygous mutations in TNFRSF13B are also associated with CVID, whereas the other 3 genes are recessive. Those with a mutation in the TNFRSF13B gene may require further investigation. […] Autosomal dominant CVID has been linked to chromosome 4q. One study supports the existence of a disease-causing gene for autosomal dominant CVID/IgA deficiency on chromosome 4q. Other possible loci for dominant CVID genes are on chromosomes 5p and 16q.

• #24 Common variable immunodeficiency and autoimmune diseases: A 10-year single-center experience | Volume 39 – Issue 4 – December 2024 | Archives of Rheumatology

  https://www.archivesofrheumatology.org/full-text/1626

  Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency, with an estimated incidence of 1 in 50,000 to 20,000. The pathogenesis of CVID is still unknown. The loss of B-cell function is a common immune defect in all CVID patients. This defect may also result from a deficiency of other cells that help in antibody production. In most cases, it is accompanied by a decrease in the number and percentage of class-switched memory B (cSMB) cells and plasma cell loss. These patients have a propensity for autoimmune and inflammatory conditions, potentially due to a defect in the standard mechanisms that allow tolerance to be established. Therefore, genetic mutations associated with autoimmunity should be considered, specifically in CVID patients with autoimmune conditions.

• #25 Common variable immunodeficiency – an update | Arthritis Research & Therapy | Full Text

  https://arthritis-research.biomedcentral.com/articles/10.1186/ar4032

  The disturbed memory B-cell formation points towards an impaired germinal center reaction in secondary lymphoid organs of most CVID patients. This assumption is further supported by decreased rates of somatic hypermutations in CD27+ B cells of CVID patients, a phenomenon that inversely correlates with an increased risk of chronic lung damage. […] Currently, defects of B-cell receptor activation as well as the TLRs have been identified in subgroups of patients. The underlying cause remains unknown for both defects. […] When DCs from CVID patients were differentiated in cell culture experiments their maturation was impaired, resulting in diminished interleukin-12 production and impaired up-regulation of co-stimulatory molecules. This might limit the ability of CVID DCs to contact and successfully interact with T cells. […] The recently described relationship between TACI and the TLR9 signaling pathway strengthens the assumption that these disturbances of the TLR system in CVID patients are of pathophysiological relevance even though no genetic mutations in the TLR pathway have been established so far.

• #26 Common Variable Immunodeficiency – Page 6 of 7 – The Rheumatologist

  https://www.the-rheumatologist.org/article/common-variable-immunodeficiency/6/?singlepage=1

  Common variable immunodeficiency (CVID) has been recognized as the most common symptomatic form of antibody deficiency diagnosed in adulthood since its first description by Janeway and colleagues. […] Recent discoveries in the molecular genetics and immunologic basis of this disease have shed important new light on its pathogenesis and raised prospects for earlier and better diagnosis and treatment. […] CVID pathogenesis has been attributed to defects in T cells and their subsets, antigen presenting cells, and B cells. Despite convincing evidence that alterations of T cell function and subset distribution are associated with the CVID phenotype, recent research points to the impaired terminal differentiation of B lymphocytes as the hallmark of the disease. […] Several groups have now demonstrated that the formation of memory B cells is severely impaired in the majority of CVID patients and leads to a concomitant depletion of long-lived plasma cells and a drop of serum Ig levels.

• #27 Common Variable Immunodeficiency – Page 3 of 7 – The Rheumatologist

  https://www.the-rheumatologist.org/article/common-variable-immunodeficiency/3/?singlepage=1

  Several groups have now demonstrated that the formation of memory B cells is severely impaired in the majority of CVID patients and leads to a concomitant depletion of long-lived plasma cells and a drop of serum Ig levels. The altered distribution of B cell subsets observed in CVID patients is now applied in disease classification. […] It has long been known that CVID also has a genetic component. While most cases of this disease occur sporadically, in 10% to 20% of CVID cases, at least one additional family member either suffers from CVID or selective IgA deficiency. Genetic linkage studies have revealed that the genetic defect involved in this disease cannot be reduced to a single gene locus. […] Candidate loci for CVID have now been demonstrated at the HLA region on chromosome 6, chromosome 4q, and chromosome 16q. This genetic heterogeneity which probably mirrors the variable clinical presentation of this disease is further increased by the recent discovery of four candidate genes which were found to be mutated in CVID independently of the results of previous linkage and association studies. These genes ICOS, TACI, CD19, and BAFFR encode for cell surface receptors on lymphocytes that play crucial roles either in peripheral B cell development or in B cell function.

• #28 Common Variable Immunodeficiency – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549787/

  The clinical variability of CVID suggests that multiple immunoregulatory defects can result in the final common pathway of hypogammaglobulinemia. […] Reports exist of numerous immune-system abnormalities, the most common of which is defective antibody formation. […] The number of B cells is normal in the majority of patients, but many of them have reduced percentages of isotype-switched memory B cells capable of producing immunoglobin isotypes that are critical toward antibody response recall. […] B cell maturation is defective, and the action of toll-like receptors 7 and 9 (TLR7 and TLR9) becomes impaired because of a yet unknown mechanism. […] Determining the number of isotype-switched memory B cells is of utmost interest because it provides information about the immaturity of the B cell, relates to the numbers of plasma cells in the bone marrow, and gives information about the possible clinical outcomes.

• #29 Common Variable Immunodeficiency | Select 5-Minute Pediatrics Topics

  https://www.unboundmedicine.com/5minute/view/Select-5-Minute-Pediatric-Consult/14174/all/Common_Variable_Immunodeficiency?q=Abdominal+pain

  Main characteristic is hypogammaglobulinemia. […] Impaired immunoglobulin and specific antibody production despite normal B cell numbers. […] Often increased proportion of immature B cells. […] Deficiency of class-switched memory B cells associated with more complex disease (autoimmunity, granulomatous disease, hypersplenism, and lymphoid hyperplasia). […] Functional defects of both B and T lymphocytes are described.

• #30 Common Variable Immunodeficiency: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1051103-overview

  In patients with common variable immunodeficiency (CVID), numerous immune-system abnormalities are reported, the most common of which is defective antibody formation. Consequently, both humoral and cell-mediated lymphocytic responses are affected. Some CVID patients may have a defect in the T-cell ability to help B cells, and/or B-cell response to T-cell help. Innate immunity defects may modify clinical status and findings in these patients. […] The basic pathophysiologic process in CVID is a simple failure in the differentiation of B lymphocytes. However, evidence shows that this defect in the pathway is not common among patients. One study showed that, when B lymphocytes were stimulated with pokeweed mitogen in vitro, plasma cells failed to differentiate, even in the presence of normal T cells. This finding suggests a defect in B-cell expression in surface molecules. Such cellular deficits have been traced to the second messenger and translocation pathways of B cells. These deficits include problems with protein kinase C activation and tyrosine phosphorylation. Findings from other studies suggest the complete absence of IgG and IgA production, an increased rate of spontaneous apoptosis, impaired DNA repair, and the presence somatic mutations affecting B-cell regulation.

• #31 Common Variable Immunodeficiency and Selective IgA Deficiency: Focus on Autoimmune Manifestations and Their Pathogenesis

  https://www.mdpi.com/2673-8937/3/4/31

  The pathophysiology of CVID is rather mysterious, despite the progress in molecular biology, immunophenotyping, and genetics. […] The peripheral selection of memory B cells appears to be impaired in CVID with an autoimmune phenotype: a low number of switched memory B cells and CD27+, based on total blood lymphocytes, is an independent risk factor for autoimmune disease, granuloma formation, and splenomegaly. […] TACI and BAFF-R defects, found in 20–30% of CVID patients, impairing B cell maturation and class-switch recombination of the mature B cell, are associated with variable autoimmune manifestations. […] The coexistence of T and B cell alterations can explain both the hypogammaglobulinemia and the other complications: autoimmunity, lymphoma, inflammation. […] Autoimmunity is the second-most common manifestation both in CVID and in SIgAD, with a prevalence of 30% in CVID and 25–33% in SigAD.

• #32

  https://omim.org/entry/607594

  Farrington et al. (1994) found that 23 of 31 patients (74%) with CVID also had a T-cell defect, whereas the remaining 8 patients did not. Patients with T-cell dysfunction could be further subdivided into those with a broader defect (n = 11) resulting in depressed expression of gp39 (CD40LG; 300386) and variable lymphokine deficiency; others had a more selective defect of either CD40 ligand expression (n = 2) or deficiency of 1 particular lymphokine (n = 10). Thus, CVID may arise from a number of different molecular aberrations. Inefficient signaling via CD40 may be responsible, in part, for failure of B-cell differentiation in some patients with CVID. […] In a study of 8 patients, including 6 with CVID and 2 with slightly less severe hypogammaglobulinemia and recurrent infections, Levy et al. (1998) found that 2 CVID patients had a dramatic reduction in somatic hypermutation in the variable (V) region of Ig genes. Between 40 and 75% of IgG transcripts were totally devoid of somatic mutation in the circulating memory B-cell compartment. Since functional assays of the T-cell compartment were normal, the findings pointed to an intrinsic B-cell defect in the process of antibody affinity maturation in CVID.

• #33 Common variable immunodeficiency – an update | Arthritis Research & Therapy | Full Text

  https://arthritis-research.biomedcentral.com/articles/10.1186/ar4032

  The disturbed memory B-cell formation points towards an impaired germinal center reaction in secondary lymphoid organs of most CVID patients. This assumption is further supported by decreased rates of somatic hypermutations in CD27+ B cells of CVID patients, a phenomenon that inversely correlates with an increased risk of chronic lung damage. […] Currently, defects of B-cell receptor activation as well as the TLRs have been identified in subgroups of patients. The underlying cause remains unknown for both defects. […] When DCs from CVID patients were differentiated in cell culture experiments their maturation was impaired, resulting in diminished interleukin-12 production and impaired up-regulation of co-stimulatory molecules. This might limit the ability of CVID DCs to contact and successfully interact with T cells. […] The recently described relationship between TACI and the TLR9 signaling pathway strengthens the assumption that these disturbances of the TLR system in CVID patients are of pathophysiological relevance even though no genetic mutations in the TLR pathway have been established so far.

• #34 Common Variable Immunodeficiency – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549787/

  The clinical variability of CVID suggests that multiple immunoregulatory defects can result in the final common pathway of hypogammaglobulinemia. […] Reports exist of numerous immune-system abnormalities, the most common of which is defective antibody formation. […] The number of B cells is normal in the majority of patients, but many of them have reduced percentages of isotype-switched memory B cells capable of producing immunoglobin isotypes that are critical toward antibody response recall. […] B cell maturation is defective, and the action of toll-like receptors 7 and 9 (TLR7 and TLR9) becomes impaired because of a yet unknown mechanism. […] Determining the number of isotype-switched memory B cells is of utmost interest because it provides information about the immaturity of the B cell, relates to the numbers of plasma cells in the bone marrow, and gives information about the possible clinical outcomes.

• #35 Common variable immunodeficiency – an update | Arthritis Research & Therapy | Full Text

  https://arthritis-research.biomedcentral.com/articles/10.1186/ar4032

  The disturbed memory B-cell formation points towards an impaired germinal center reaction in secondary lymphoid organs of most CVID patients. This assumption is further supported by decreased rates of somatic hypermutations in CD27+ B cells of CVID patients, a phenomenon that inversely correlates with an increased risk of chronic lung damage. […] Currently, defects of B-cell receptor activation as well as the TLRs have been identified in subgroups of patients. The underlying cause remains unknown for both defects. […] When DCs from CVID patients were differentiated in cell culture experiments their maturation was impaired, resulting in diminished interleukin-12 production and impaired up-regulation of co-stimulatory molecules. This might limit the ability of CVID DCs to contact and successfully interact with T cells. […] The recently described relationship between TACI and the TLR9 signaling pathway strengthens the assumption that these disturbances of the TLR system in CVID patients are of pathophysiological relevance even though no genetic mutations in the TLR pathway have been established so far.

• #36 Common Variable Immunodeficiency: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1051103-overview

  In patients with common variable immunodeficiency (CVID), numerous immune-system abnormalities are reported, the most common of which is defective antibody formation. Consequently, both humoral and cell-mediated lymphocytic responses are affected. Some CVID patients may have a defect in the T-cell ability to help B cells, and/or B-cell response to T-cell help. Innate immunity defects may modify clinical status and findings in these patients. […] The basic pathophysiologic process in CVID is a simple failure in the differentiation of B lymphocytes. However, evidence shows that this defect in the pathway is not common among patients. One study showed that, when B lymphocytes were stimulated with pokeweed mitogen in vitro, plasma cells failed to differentiate, even in the presence of normal T cells. This finding suggests a defect in B-cell expression in surface molecules. Such cellular deficits have been traced to the second messenger and translocation pathways of B cells. These deficits include problems with protein kinase C activation and tyrosine phosphorylation. Findings from other studies suggest the complete absence of IgG and IgA production, an increased rate of spontaneous apoptosis, impaired DNA repair, and the presence somatic mutations affecting B-cell regulation.

• #37 Common variable immunodeficiency – Wikipedia

  https://en.wikipedia.org/wiki/Common_variable_immunodeficiency

  Common variable immunodeficiency (CVID) is an inborn immune disorder characterized by recurrent infections and low antibody levels, specifically in immunoglobulin (Ig) types IgG, IgM, and IgA. […] The causative factors of CVID are not fully known. Genetic mutations can be identified as the cause of disease in about 10% of people, while familial inheritance accounts for 10-25% of cases. Rather than arising from a single genetic mutation, CVID seems to result from a variety of mutations that all contribute to a failure in antibody production. […] Mutations in the genes encoding ICOS, TACI, CD19, CD20, CD21, CD80, and BAFFR have been identified as causative of CVID. […] The majority of CVID patients have normal B cell counts, suggesting the impaired antibody production is mainly a defect in the differentiation process of B cells into memory and plasma cells.

• #38 Common variable immune deficiency (CVID) – Australasian Society of Clinical Immunology and Allergy (ASCIA)

  https://www.allergy.org.au/patients/immunodeficiencies/common-variable-immune-deficiency-cvid

  Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiency (PID) disorders. […] In most cases the causes of CVID are not known. Studies have identified a small number of abnormal genes that are involved in immune cell development in around one in ten people with CVID. […] Most people with CVID have normal numbers of B cells. However, these B cells do not mature properly to produce effective antibodies, or they don’t receive the help needed from T cells, to develop normal antibody responses. […] People with CVID will vary in their ability to make effective antibody responses, due to decreased levels of: All three major types of immunoglobulins (IgG, IgA and IgM) or Immunoglobulins G and A (IgG, IgA) or Only Immunoglobulin G (IgG). […] Most people with CVID have frequent infections due to their reduced antibody responses.

• #39 Common Variable Immunodeficiency – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549787/

  The clinical variability of CVID suggests that multiple immunoregulatory defects can result in the final common pathway of hypogammaglobulinemia. […] Reports exist of numerous immune-system abnormalities, the most common of which is defective antibody formation. […] The number of B cells is normal in the majority of patients, but many of them have reduced percentages of isotype-switched memory B cells capable of producing immunoglobin isotypes that are critical toward antibody response recall. […] B cell maturation is defective, and the action of toll-like receptors 7 and 9 (TLR7 and TLR9) becomes impaired because of a yet unknown mechanism. […] Determining the number of isotype-switched memory B cells is of utmost interest because it provides information about the immaturity of the B cell, relates to the numbers of plasma cells in the bone marrow, and gives information about the possible clinical outcomes.

• #40 Common Variable Immunodeficiency: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1051103-overview

  Common variable immunodeficiency (CVID), the most common clinical primary immunodeficiency in adults, is a disorder that involves the following: (1) low levels of most or all of the immunoglobulin (Ig) classes, (2) a lack of B lymphocytes or plasma cells that are capable of producing antibodies, and (3) frequent bacterial infections. A diagnosis of CVID is reserved for those with an undefined B-cell dysfunction. Combining DNA sequencing with gene expression, methylation, proteomic, and metabolomics data holds the promise of greatly expanding knowledge about CVID. CVID is diverse, both in its clinical presentation and in the types of deficiency. Although decreased serum levels of immunoglobulin G (IgG) and immunoglobulin A (IgA) are characteristic, approximately 50% of patients with the deficiency also have diminished serum immunoglobulin M (IgM) levels and T-lymphocyte dysfunction. In CVID, the T-cell compartment is strongly impacted, with premature arrest in thymic output, leading to T-cell exhaustion and immune dysregulation. About 20% of those with CVID develop an autoimmune disease. In addition, autoinflammatory, granulomatous, and/or lymphoproliferative disorders may become evident.

• #41 Common variable immune deficiency (CVID) | Immune Deficiency Foundation

  https://primaryimmune.org/understanding-primary-immunodeficiency/types-of-pi/common-variable-immune-deficiency-cvid

  Common variable immune deficiency (CVID), previously known as adult-onset hypogammaglobulinemia, is one of the most frequently diagnosed primary immunodeficiencies. It is characterized by low levels of serum antibodies, which cause an increased susceptibility to infection. […] An additional characteristic is a decreased IgA and/or IgM level, or a low level of all three major types of immunoglobulins (IgG, IgA, and IgM). In some individuals, there are defects of the T cells, and this may also contribute to increased susceptibility to infections as well as autoimmunity, granulomatous disease, and cancer. […] Although people with CVID have depressed antibody responses and low levels of immunoglobulins in their blood, some of the antibodies they produce may attack their own tissues (autoantibodies).

• #42 Common Variable Immunodeficiency – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549787/

  Decreased T lymphocyte proliferation to mitogens and antigens, reduced T regulatory cells, T cell receptor excision circles that suggest thymic dysregulation, defective T cell receptor signal transduction. […] The minor capacity of dendritic cells to secrete interleukin-12. […] A drop of plasma cells in the gastrointestinal tract and bone marrow.

• #43 Common Variable Immunodeficiency – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549787/

  Decreased T lymphocyte proliferation to mitogens and antigens, reduced T regulatory cells, T cell receptor excision circles that suggest thymic dysregulation, defective T cell receptor signal transduction. […] The minor capacity of dendritic cells to secrete interleukin-12. […] A drop of plasma cells in the gastrointestinal tract and bone marrow.

• #44 Common Variable Immunodeficiency and Selective IgA Deficiency: Focus on Autoimmune Manifestations and Their Pathogenesis

  https://www.mdpi.com/2673-8937/3/4/31

  The increased risk of autoimmune manifestations in patients with CVID/SIgAD has several possible explanations, among which include B and T cell defects, a low rate of isotype-switched B/T memory cells, a reduction in Tregs, the microbiota–immune axis, and molecular mimicry. […] Autoimmune cytopenia represents the majority of autoimmune manifestations of CVID and in 60% of cases, cytopenia precedes hypogammaglobulinemia in the diagnosis of CVID. […] Autoimmune thrombocytopenic purpura is the autoimmune disease most frequently associated with CVID. […] The significant association between enteropathy and liver disease in CVID/SIgAD may be due to the inflammatory response to pathogens delivered from the leaky gut to the liver through the portal vein, or due to a different common pathophysiological basis resulting in T cell-mediated liver damage.

• #45 Common Variable Immunodeficiency – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549787/

  Decreased T lymphocyte proliferation to mitogens and antigens, reduced T regulatory cells, T cell receptor excision circles that suggest thymic dysregulation, defective T cell receptor signal transduction. […] The minor capacity of dendritic cells to secrete interleukin-12. […] A drop of plasma cells in the gastrointestinal tract and bone marrow.

• #46 Common Variable Immunodeficiency – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549787/

  Decreased T lymphocyte proliferation to mitogens and antigens, reduced T regulatory cells, T cell receptor excision circles that suggest thymic dysregulation, defective T cell receptor signal transduction. […] The minor capacity of dendritic cells to secrete interleukin-12. […] A drop of plasma cells in the gastrointestinal tract and bone marrow.

• #47 Common Variable Immunodeficiency: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1051103-overview

  A number of factors and cofactors stimulate Ig secretion from B cells harvested from patients with CVID. These factors include B-cell mitogens, soluble T-cell factors, specific B-cell differentiation factors, the Epstein-Barr virus, interleukin 2 (IL-2), interleukin 4 (IL-4), and interleukin 10 (IL-10). Perhaps the most potent stimulant is the CD40 ligand, which is expressed by activated CD4+ cells. In fact, in 40% of patients with CVID, the CD40 ligand is expressed in low levels on activated T cells. In these patients, decreased IL-2 production after T-cell receptor stimulation is also present. […] A common defect is the response to antigens by CD4+ T lymphocytes. After immunization, some patients with CVID have decreased numbers of circulating responsive CD4+ T cells. Other patients have an increased number of CD4+ T cells, but they also have an increased rate of apoptosis of these cells. Signal transduction appears to be the primary defect in these T cells.

• #48 Common Variable Immunodeficiency: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1051103-overview

  Of all patients with CVID, 25-30% often have increased numbers of CD8+ T cells and a reduced CD4/CD8 ratio. The cause is an increase in cyclic adenosine monophosphate levels and the increased activation of protein kinase A. On physical examination, patients with this subtype often have splenomegaly and bronchiectasis. In addition, 60% of patients with CVID have a diminished response to T-cell receptor stimulation and expression of receptors for IL-2, IL-4, interleukin 5 (IL-5), and interferon gamma. However, the T-cell receptors show no evidence of abnormality; in fact, genetic findings indicate normal heterogeneity of the genetic rearrangements. Therefore, most patients with CVID can be said to have antibody deficiency secondary to T-cell signaling abnormalities, as well as defective interactions between T and B lymphocytes.

• #49 Common Variable Immunodeficiency: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1051103-overview

  A number of factors and cofactors stimulate Ig secretion from B cells harvested from patients with CVID. These factors include B-cell mitogens, soluble T-cell factors, specific B-cell differentiation factors, the Epstein-Barr virus, interleukin 2 (IL-2), interleukin 4 (IL-4), and interleukin 10 (IL-10). Perhaps the most potent stimulant is the CD40 ligand, which is expressed by activated CD4+ cells. In fact, in 40% of patients with CVID, the CD40 ligand is expressed in low levels on activated T cells. In these patients, decreased IL-2 production after T-cell receptor stimulation is also present. […] A common defect is the response to antigens by CD4+ T lymphocytes. After immunization, some patients with CVID have decreased numbers of circulating responsive CD4+ T cells. Other patients have an increased number of CD4+ T cells, but they also have an increased rate of apoptosis of these cells. Signal transduction appears to be the primary defect in these T cells.

• #50 Common Variable Immunodeficiency: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1051103-overview

  Of all patients with CVID, 25-30% often have increased numbers of CD8+ T cells and a reduced CD4/CD8 ratio. The cause is an increase in cyclic adenosine monophosphate levels and the increased activation of protein kinase A. On physical examination, patients with this subtype often have splenomegaly and bronchiectasis. In addition, 60% of patients with CVID have a diminished response to T-cell receptor stimulation and expression of receptors for IL-2, IL-4, interleukin 5 (IL-5), and interferon gamma. However, the T-cell receptors show no evidence of abnormality; in fact, genetic findings indicate normal heterogeneity of the genetic rearrangements. Therefore, most patients with CVID can be said to have antibody deficiency secondary to T-cell signaling abnormalities, as well as defective interactions between T and B lymphocytes.

• #51 Common Variable Immunodeficiency – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549787/

  Decreased T lymphocyte proliferation to mitogens and antigens, reduced T regulatory cells, T cell receptor excision circles that suggest thymic dysregulation, defective T cell receptor signal transduction. […] The minor capacity of dendritic cells to secrete interleukin-12. […] A drop of plasma cells in the gastrointestinal tract and bone marrow.

• #52 Common variable immunodeficiency – an update | Arthritis Research & Therapy | Full Text

  https://arthritis-research.biomedcentral.com/articles/10.1186/ar4032

  The disturbed memory B-cell formation points towards an impaired germinal center reaction in secondary lymphoid organs of most CVID patients. This assumption is further supported by decreased rates of somatic hypermutations in CD27+ B cells of CVID patients, a phenomenon that inversely correlates with an increased risk of chronic lung damage. […] Currently, defects of B-cell receptor activation as well as the TLRs have been identified in subgroups of patients. The underlying cause remains unknown for both defects. […] When DCs from CVID patients were differentiated in cell culture experiments their maturation was impaired, resulting in diminished interleukin-12 production and impaired up-regulation of co-stimulatory molecules. This might limit the ability of CVID DCs to contact and successfully interact with T cells. […] The recently described relationship between TACI and the TLR9 signaling pathway strengthens the assumption that these disturbances of the TLR system in CVID patients are of pathophysiological relevance even though no genetic mutations in the TLR pathway have been established so far.

• #53 Common variable immunodeficiency – an update | Arthritis Research & Therapy | Full Text

  https://arthritis-research.biomedcentral.com/articles/10.1186/ar4032

  The disturbed memory B-cell formation points towards an impaired germinal center reaction in secondary lymphoid organs of most CVID patients. This assumption is further supported by decreased rates of somatic hypermutations in CD27+ B cells of CVID patients, a phenomenon that inversely correlates with an increased risk of chronic lung damage. […] Currently, defects of B-cell receptor activation as well as the TLRs have been identified in subgroups of patients. The underlying cause remains unknown for both defects. […] When DCs from CVID patients were differentiated in cell culture experiments their maturation was impaired, resulting in diminished interleukin-12 production and impaired up-regulation of co-stimulatory molecules. This might limit the ability of CVID DCs to contact and successfully interact with T cells. […] The recently described relationship between TACI and the TLR9 signaling pathway strengthens the assumption that these disturbances of the TLR system in CVID patients are of pathophysiological relevance even though no genetic mutations in the TLR pathway have been established so far.

• #54 Common Variable Immunodeficiency – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549787/

  Decreased T lymphocyte proliferation to mitogens and antigens, reduced T regulatory cells, T cell receptor excision circles that suggest thymic dysregulation, defective T cell receptor signal transduction. […] The minor capacity of dendritic cells to secrete interleukin-12. […] A drop of plasma cells in the gastrointestinal tract and bone marrow.

• #55 Common Variable Immunodeficiency: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1051103-overview

  A number of factors and cofactors stimulate Ig secretion from B cells harvested from patients with CVID. These factors include B-cell mitogens, soluble T-cell factors, specific B-cell differentiation factors, the Epstein-Barr virus, interleukin 2 (IL-2), interleukin 4 (IL-4), and interleukin 10 (IL-10). Perhaps the most potent stimulant is the CD40 ligand, which is expressed by activated CD4+ cells. In fact, in 40% of patients with CVID, the CD40 ligand is expressed in low levels on activated T cells. In these patients, decreased IL-2 production after T-cell receptor stimulation is also present. […] A common defect is the response to antigens by CD4+ T lymphocytes. After immunization, some patients with CVID have decreased numbers of circulating responsive CD4+ T cells. Other patients have an increased number of CD4+ T cells, but they also have an increased rate of apoptosis of these cells. Signal transduction appears to be the primary defect in these T cells.

• #56 Common Variable Immunodeficiency: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1051103-overview

  A number of factors and cofactors stimulate Ig secretion from B cells harvested from patients with CVID. These factors include B-cell mitogens, soluble T-cell factors, specific B-cell differentiation factors, the Epstein-Barr virus, interleukin 2 (IL-2), interleukin 4 (IL-4), and interleukin 10 (IL-10). Perhaps the most potent stimulant is the CD40 ligand, which is expressed by activated CD4+ cells. In fact, in 40% of patients with CVID, the CD40 ligand is expressed in low levels on activated T cells. In these patients, decreased IL-2 production after T-cell receptor stimulation is also present. […] A common defect is the response to antigens by CD4+ T lymphocytes. After immunization, some patients with CVID have decreased numbers of circulating responsive CD4+ T cells. Other patients have an increased number of CD4+ T cells, but they also have an increased rate of apoptosis of these cells. Signal transduction appears to be the primary defect in these T cells.

• #57 Common Variable Immunodeficiency: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1051103-overview

  A number of factors and cofactors stimulate Ig secretion from B cells harvested from patients with CVID. These factors include B-cell mitogens, soluble T-cell factors, specific B-cell differentiation factors, the Epstein-Barr virus, interleukin 2 (IL-2), interleukin 4 (IL-4), and interleukin 10 (IL-10). Perhaps the most potent stimulant is the CD40 ligand, which is expressed by activated CD4+ cells. In fact, in 40% of patients with CVID, the CD40 ligand is expressed in low levels on activated T cells. In these patients, decreased IL-2 production after T-cell receptor stimulation is also present. […] A common defect is the response to antigens by CD4+ T lymphocytes. After immunization, some patients with CVID have decreased numbers of circulating responsive CD4+ T cells. Other patients have an increased number of CD4+ T cells, but they also have an increased rate of apoptosis of these cells. Signal transduction appears to be the primary defect in these T cells.

• #58 Common Variable Immunodeficiency: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/1051103-overview

  A number of factors and cofactors stimulate Ig secretion from B cells harvested from patients with CVID. These factors include B-cell mitogens, soluble T-cell factors, specific B-cell differentiation factors, the Epstein-Barr virus, interleukin 2 (IL-2), interleukin 4 (IL-4), and interleukin 10 (IL-10). Perhaps the most potent stimulant is the CD40 ligand, which is expressed by activated CD4+ cells. In fact, in 40% of patients with CVID, the CD40 ligand is expressed in low levels on activated T cells. In these patients, decreased IL-2 production after T-cell receptor stimulation is also present. […] A common defect is the response to antigens by CD4+ T lymphocytes. After immunization, some patients with CVID have decreased numbers of circulating responsive CD4+ T cells. Other patients have an increased number of CD4+ T cells, but they also have an increased rate of apoptosis of these cells. Signal transduction appears to be the primary defect in these T cells.

• #59

  https://omim.org/entry/607594

  Holm et al. (2003) found that T cells from CVID patients activated by anti-CD3 (see 186740) and anti-CD28 (186760) secreted less IL10 (124092) than healthy controls, regardless of proportions of T-cell subsets. Furthermore, sensitivity to cAMP-dependent inhibition of protein kinase A type I (see 188830)-mediated T-cell activation was greater in CVID patients. Holm et al. (2003) proposed that impaired IL10 secretion by CVID patient T cells may be a link between T-cell deficiency and impaired B-cell function in CVID. […] Using flow cytometry to assess the immunologic profiles of 32 patients with CVID, Cunningham-Rundles et al. (2006) found that, in addition to reduced levels of CD27 (TNFRSF7; 186711)-positive memory B cells, CVID patients had unrelated, pronounced TLR9 (605474) defects. CpG oligonucleotides did not activate CVID B cells, even when costimulated by B-cell receptor, and they did not stimulate surface or intracytoplasmic expression of TLR9 or production of IL6 (147620) or IL10. In addition, CVID plasmacytoid dendritic cells, which expressed normal amounts of intracytoplasmic TLR9, produced only low amounts of IFNA (147660). No TLR9 mutations or polymorphisms were detected. Cunningham-Rundles et al. (2006) concluded that CVID patients have broad TLR9 activation defects that result in impaired CpG-initiated innate immunity.

• #60

  https://omim.org/entry/607594

  Holm et al. (2003) found that T cells from CVID patients activated by anti-CD3 (see 186740) and anti-CD28 (186760) secreted less IL10 (124092) than healthy controls, regardless of proportions of T-cell subsets. Furthermore, sensitivity to cAMP-dependent inhibition of protein kinase A type I (see 188830)-mediated T-cell activation was greater in CVID patients. Holm et al. (2003) proposed that impaired IL10 secretion by CVID patient T cells may be a link between T-cell deficiency and impaired B-cell function in CVID. […] Using flow cytometry to assess the immunologic profiles of 32 patients with CVID, Cunningham-Rundles et al. (2006) found that, in addition to reduced levels of CD27 (TNFRSF7; 186711)-positive memory B cells, CVID patients had unrelated, pronounced TLR9 (605474) defects. CpG oligonucleotides did not activate CVID B cells, even when costimulated by B-cell receptor, and they did not stimulate surface or intracytoplasmic expression of TLR9 or production of IL6 (147620) or IL10. In addition, CVID plasmacytoid dendritic cells, which expressed normal amounts of intracytoplasmic TLR9, produced only low amounts of IFNA (147660). No TLR9 mutations or polymorphisms were detected. Cunningham-Rundles et al. (2006) concluded that CVID patients have broad TLR9 activation defects that result in impaired CpG-initiated innate immunity.

• #61 Common Variable Immunodeficiency – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549787/

  The clinical variability of CVID suggests that multiple immunoregulatory defects can result in the final common pathway of hypogammaglobulinemia. […] Reports exist of numerous immune-system abnormalities, the most common of which is defective antibody formation. […] The number of B cells is normal in the majority of patients, but many of them have reduced percentages of isotype-switched memory B cells capable of producing immunoglobin isotypes that are critical toward antibody response recall. […] B cell maturation is defective, and the action of toll-like receptors 7 and 9 (TLR7 and TLR9) becomes impaired because of a yet unknown mechanism. […] Determining the number of isotype-switched memory B cells is of utmost interest because it provides information about the immaturity of the B cell, relates to the numbers of plasma cells in the bone marrow, and gives information about the possible clinical outcomes.

• #62

  https://omim.org/entry/607594

  Holm et al. (2003) found that T cells from CVID patients activated by anti-CD3 (see 186740) and anti-CD28 (186760) secreted less IL10 (124092) than healthy controls, regardless of proportions of T-cell subsets. Furthermore, sensitivity to cAMP-dependent inhibition of protein kinase A type I (see 188830)-mediated T-cell activation was greater in CVID patients. Holm et al. (2003) proposed that impaired IL10 secretion by CVID patient T cells may be a link between T-cell deficiency and impaired B-cell function in CVID. […] Using flow cytometry to assess the immunologic profiles of 32 patients with CVID, Cunningham-Rundles et al. (2006) found that, in addition to reduced levels of CD27 (TNFRSF7; 186711)-positive memory B cells, CVID patients had unrelated, pronounced TLR9 (605474) defects. CpG oligonucleotides did not activate CVID B cells, even when costimulated by B-cell receptor, and they did not stimulate surface or intracytoplasmic expression of TLR9 or production of IL6 (147620) or IL10. In addition, CVID plasmacytoid dendritic cells, which expressed normal amounts of intracytoplasmic TLR9, produced only low amounts of IFNA (147660). No TLR9 mutations or polymorphisms were detected. Cunningham-Rundles et al. (2006) concluded that CVID patients have broad TLR9 activation defects that result in impaired CpG-initiated innate immunity.

• #63

  https://omim.org/entry/607594

  Holm et al. (2003) found that T cells from CVID patients activated by anti-CD3 (see 186740) and anti-CD28 (186760) secreted less IL10 (124092) than healthy controls, regardless of proportions of T-cell subsets. Furthermore, sensitivity to cAMP-dependent inhibition of protein kinase A type I (see 188830)-mediated T-cell activation was greater in CVID patients. Holm et al. (2003) proposed that impaired IL10 secretion by CVID patient T cells may be a link between T-cell deficiency and impaired B-cell function in CVID. […] Using flow cytometry to assess the immunologic profiles of 32 patients with CVID, Cunningham-Rundles et al. (2006) found that, in addition to reduced levels of CD27 (TNFRSF7; 186711)-positive memory B cells, CVID patients had unrelated, pronounced TLR9 (605474) defects. CpG oligonucleotides did not activate CVID B cells, even when costimulated by B-cell receptor, and they did not stimulate surface or intracytoplasmic expression of TLR9 or production of IL6 (147620) or IL10. In addition, CVID plasmacytoid dendritic cells, which expressed normal amounts of intracytoplasmic TLR9, produced only low amounts of IFNA (147660). No TLR9 mutations or polymorphisms were detected. Cunningham-Rundles et al. (2006) concluded that CVID patients have broad TLR9 activation defects that result in impaired CpG-initiated innate immunity.

• #64

  https://omim.org/entry/607594

  Holm et al. (2003) found that T cells from CVID patients activated by anti-CD3 (see 186740) and anti-CD28 (186760) secreted less IL10 (124092) than healthy controls, regardless of proportions of T-cell subsets. Furthermore, sensitivity to cAMP-dependent inhibition of protein kinase A type I (see 188830)-mediated T-cell activation was greater in CVID patients. Holm et al. (2003) proposed that impaired IL10 secretion by CVID patient T cells may be a link between T-cell deficiency and impaired B-cell function in CVID. […] Using flow cytometry to assess the immunologic profiles of 32 patients with CVID, Cunningham-Rundles et al. (2006) found that, in addition to reduced levels of CD27 (TNFRSF7; 186711)-positive memory B cells, CVID patients had unrelated, pronounced TLR9 (605474) defects. CpG oligonucleotides did not activate CVID B cells, even when costimulated by B-cell receptor, and they did not stimulate surface or intracytoplasmic expression of TLR9 or production of IL6 (147620) or IL10. In addition, CVID plasmacytoid dendritic cells, which expressed normal amounts of intracytoplasmic TLR9, produced only low amounts of IFNA (147660). No TLR9 mutations or polymorphisms were detected. Cunningham-Rundles et al. (2006) concluded that CVID patients have broad TLR9 activation defects that result in impaired CpG-initiated innate immunity.

• #65

  https://omim.org/entry/607594

  Holm et al. (2003) found that T cells from CVID patients activated by anti-CD3 (see 186740) and anti-CD28 (186760) secreted less IL10 (124092) than healthy controls, regardless of proportions of T-cell subsets. Furthermore, sensitivity to cAMP-dependent inhibition of protein kinase A type I (see 188830)-mediated T-cell activation was greater in CVID patients. Holm et al. (2003) proposed that impaired IL10 secretion by CVID patient T cells may be a link between T-cell deficiency and impaired B-cell function in CVID. […] Using flow cytometry to assess the immunologic profiles of 32 patients with CVID, Cunningham-Rundles et al. (2006) found that, in addition to reduced levels of CD27 (TNFRSF7; 186711)-positive memory B cells, CVID patients had unrelated, pronounced TLR9 (605474) defects. CpG oligonucleotides did not activate CVID B cells, even when costimulated by B-cell receptor, and they did not stimulate surface or intracytoplasmic expression of TLR9 or production of IL6 (147620) or IL10. In addition, CVID plasmacytoid dendritic cells, which expressed normal amounts of intracytoplasmic TLR9, produced only low amounts of IFNA (147660). No TLR9 mutations or polymorphisms were detected. Cunningham-Rundles et al. (2006) concluded that CVID patients have broad TLR9 activation defects that result in impaired CpG-initiated innate immunity.

• #66 Common variable immunodeficiency – an update | Arthritis Research & Therapy | Full Text

  https://arthritis-research.biomedcentral.com/articles/10.1186/ar4032

  The disturbed memory B-cell formation points towards an impaired germinal center reaction in secondary lymphoid organs of most CVID patients. This assumption is further supported by decreased rates of somatic hypermutations in CD27+ B cells of CVID patients, a phenomenon that inversely correlates with an increased risk of chronic lung damage. […] Currently, defects of B-cell receptor activation as well as the TLRs have been identified in subgroups of patients. The underlying cause remains unknown for both defects. […] When DCs from CVID patients were differentiated in cell culture experiments their maturation was impaired, resulting in diminished interleukin-12 production and impaired up-regulation of co-stimulatory molecules. This might limit the ability of CVID DCs to contact and successfully interact with T cells. […] The recently described relationship between TACI and the TLR9 signaling pathway strengthens the assumption that these disturbances of the TLR system in CVID patients are of pathophysiological relevance even though no genetic mutations in the TLR pathway have been established so far.

• #67

  https://link.springer.com/article/10.1007/s10238-023-01006-3

  Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by low levels of serum immunoglobulins and increased susceptibility to infections, autoimmune disorders and cancer. […] Compelling evidences support a linkage between the gut microbiome and the CVID pathogenesis, therefore a potential for microbiome-based treatments to be a therapeutic pathway for this disorder. […] Emerging evidence highlights that both the intestinal ecosystem and the gut microbiota are profoundly disrupted in patients with CVID. […] Recent evidence indicates that CVID patients with enteropathy have a more marked transcriptional response to gut viruses. […] Microbial dysbiosis may worsen the damage to the gut barrier and lead to the translocation of bacteria or their fragments and metabolites, promoting systemic inflammation and liver injury.

• #68

  https://link.springer.com/article/10.1007/s10238-023-01006-3

  Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by low levels of serum immunoglobulins and increased susceptibility to infections, autoimmune disorders and cancer. […] Compelling evidences support a linkage between the gut microbiome and the CVID pathogenesis, therefore a potential for microbiome-based treatments to be a therapeutic pathway for this disorder. […] Emerging evidence highlights that both the intestinal ecosystem and the gut microbiota are profoundly disrupted in patients with CVID. […] Recent evidence indicates that CVID patients with enteropathy have a more marked transcriptional response to gut viruses. […] Microbial dysbiosis may worsen the damage to the gut barrier and lead to the translocation of bacteria or their fragments and metabolites, promoting systemic inflammation and liver injury.

• #69

  https://link.springer.com/article/10.1007/s10238-023-01006-3

  Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by low levels of serum immunoglobulins and increased susceptibility to infections, autoimmune disorders and cancer. […] Compelling evidences support a linkage between the gut microbiome and the CVID pathogenesis, therefore a potential for microbiome-based treatments to be a therapeutic pathway for this disorder. […] Emerging evidence highlights that both the intestinal ecosystem and the gut microbiota are profoundly disrupted in patients with CVID. […] Recent evidence indicates that CVID patients with enteropathy have a more marked transcriptional response to gut viruses. […] Microbial dysbiosis may worsen the damage to the gut barrier and lead to the translocation of bacteria or their fragments and metabolites, promoting systemic inflammation and liver injury.

• #70

  https://link.springer.com/article/10.1007/s10238-023-01006-3

  Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by low levels of serum immunoglobulins and increased susceptibility to infections, autoimmune disorders and cancer. […] Compelling evidences support a linkage between the gut microbiome and the CVID pathogenesis, therefore a potential for microbiome-based treatments to be a therapeutic pathway for this disorder. […] Emerging evidence highlights that both the intestinal ecosystem and the gut microbiota are profoundly disrupted in patients with CVID. […] Recent evidence indicates that CVID patients with enteropathy have a more marked transcriptional response to gut viruses. […] Microbial dysbiosis may worsen the damage to the gut barrier and lead to the translocation of bacteria or their fragments and metabolites, promoting systemic inflammation and liver injury.

• #71

  https://link.springer.com/article/10.1007/s10238-023-01006-3

  Despite the increasing evidence of alteration of gut microbiome in CVID, therapeutic manipulation has only been explored as a possible target for CVID patients in one study using rifaximin. […] Mitigating dysbiosis in patients with CVID is a new pathway to be evaluated, potentially impacting clinical outcomes and survival. […] Restoration of the gut microbiota to a eubiotic state plays a critical role in the management of gastrointestinal manifestations in CVID. […] There is compelling evidence that the gut microbiome plays a pivotal role in the pathophysiology of CVID. […] The experimental and clinical development of microbiota modulators in CVID requires a multidisciplinary approach involving translational research teams. […] Studies in experimental models of CVID appear necessary to better understand the immunological and biochemical effects of modulators of the gut microbiota.

• #72 Common Variable Immunodeficiency and Selective IgA Deficiency: Focus on Autoimmune Manifestations and Their Pathogenesis

  https://www.mdpi.com/2673-8937/3/4/31

  The pathophysiology of CVID is rather mysterious, despite the progress in molecular biology, immunophenotyping, and genetics. […] The peripheral selection of memory B cells appears to be impaired in CVID with an autoimmune phenotype: a low number of switched memory B cells and CD27+, based on total blood lymphocytes, is an independent risk factor for autoimmune disease, granuloma formation, and splenomegaly. […] TACI and BAFF-R defects, found in 20–30% of CVID patients, impairing B cell maturation and class-switch recombination of the mature B cell, are associated with variable autoimmune manifestations. […] The coexistence of T and B cell alterations can explain both the hypogammaglobulinemia and the other complications: autoimmunity, lymphoma, inflammation. […] Autoimmunity is the second-most common manifestation both in CVID and in SIgAD, with a prevalence of 30% in CVID and 25–33% in SigAD.

• #73 Common variable immunodeficiency and autoimmune diseases: A 10-year single-center experience | Volume 39 – Issue 4 – December 2024 | Archives of Rheumatology

  https://www.archivesofrheumatology.org/full-text/1626

  The pathogenic mechanism of autoimmunity in CVID is paradoxical. It has been suggested that the underlying cause of autoimmunity is based on the inability of these patients to eliminate microbial antigens, leading to alternative immune pathways and an excessive and chronic inflammatory response, damaging not only infected cells but also the surrounding tissue. It is also thought that the high antigen load caused by recurrent or resistant infections causes autoimmunity by affecting tolerance through superantigens or molecular mimicry. Although the mechanisms of ADs are still controversial, they likely involve central and peripheral tolerance disorders and defects in autoreactive T and B cells. In CVID, defects in B cell maturation, CD21low B cells, and cSMB cell development can be encountered. As a result, the proportion of total B cells and cSMB cells is reduced. […] Low cSMB cell levels were reported to be an independent risk factor in predicting AD, granulomatous findings, and splenomegaly. Therefore, it may be used as a guide in the routine evaluation and follow-up of CVID and other B cell-derived diseases.

• #74 Common variable immunodeficiency and autoimmune diseases: A 10-year single-center experience | Volume 39 – Issue 4 – December 2024 | Archives of Rheumatology

  https://www.archivesofrheumatology.org/full-text/1626

  The pathogenic mechanism of autoimmunity in CVID is paradoxical. It has been suggested that the underlying cause of autoimmunity is based on the inability of these patients to eliminate microbial antigens, leading to alternative immune pathways and an excessive and chronic inflammatory response, damaging not only infected cells but also the surrounding tissue. It is also thought that the high antigen load caused by recurrent or resistant infections causes autoimmunity by affecting tolerance through superantigens or molecular mimicry. Although the mechanisms of ADs are still controversial, they likely involve central and peripheral tolerance disorders and defects in autoreactive T and B cells. In CVID, defects in B cell maturation, CD21low B cells, and cSMB cell development can be encountered. As a result, the proportion of total B cells and cSMB cells is reduced. […] Low cSMB cell levels were reported to be an independent risk factor in predicting AD, granulomatous findings, and splenomegaly. Therefore, it may be used as a guide in the routine evaluation and follow-up of CVID and other B cell-derived diseases.

• #75 Common Variable Immunodeficiency and Selective IgA Deficiency: Focus on Autoimmune Manifestations and Their Pathogenesis

  https://www.mdpi.com/2673-8937/3/4/31

  The increased risk of autoimmune manifestations in patients with CVID/SIgAD has several possible explanations, among which include B and T cell defects, a low rate of isotype-switched B/T memory cells, a reduction in Tregs, the microbiota–immune axis, and molecular mimicry. […] Autoimmune cytopenia represents the majority of autoimmune manifestations of CVID and in 60% of cases, cytopenia precedes hypogammaglobulinemia in the diagnosis of CVID. […] Autoimmune thrombocytopenic purpura is the autoimmune disease most frequently associated with CVID. […] The significant association between enteropathy and liver disease in CVID/SIgAD may be due to the inflammatory response to pathogens delivered from the leaky gut to the liver through the portal vein, or due to a different common pathophysiological basis resulting in T cell-mediated liver damage.

• #76 Common Variable Immunodeficiency and Selective IgA Deficiency: Focus on Autoimmune Manifestations and Their Pathogenesis

  https://www.mdpi.com/2673-8937/3/4/31

  The increased risk of autoimmune manifestations in patients with CVID/SIgAD has several possible explanations, among which include B and T cell defects, a low rate of isotype-switched B/T memory cells, a reduction in Tregs, the microbiota–immune axis, and molecular mimicry. […] Autoimmune cytopenia represents the majority of autoimmune manifestations of CVID and in 60% of cases, cytopenia precedes hypogammaglobulinemia in the diagnosis of CVID. […] Autoimmune thrombocytopenic purpura is the autoimmune disease most frequently associated with CVID. […] The significant association between enteropathy and liver disease in CVID/SIgAD may be due to the inflammatory response to pathogens delivered from the leaky gut to the liver through the portal vein, or due to a different common pathophysiological basis resulting in T cell-mediated liver damage.

• #77 Common Variable Immunodeficiency and Selective IgA Deficiency: Focus on Autoimmune Manifestations and Their Pathogenesis

  https://www.mdpi.com/2673-8937/3/4/31

  The increased risk of autoimmune manifestations in patients with CVID/SIgAD has several possible explanations, among which include B and T cell defects, a low rate of isotype-switched B/T memory cells, a reduction in Tregs, the microbiota–immune axis, and molecular mimicry. […] Autoimmune cytopenia represents the majority of autoimmune manifestations of CVID and in 60% of cases, cytopenia precedes hypogammaglobulinemia in the diagnosis of CVID. […] Autoimmune thrombocytopenic purpura is the autoimmune disease most frequently associated with CVID. […] The significant association between enteropathy and liver disease in CVID/SIgAD may be due to the inflammatory response to pathogens delivered from the leaky gut to the liver through the portal vein, or due to a different common pathophysiological basis resulting in T cell-mediated liver damage.

• #78 Common Variable Immunodeficiency and Selective IgA Deficiency: Focus on Autoimmune Manifestations and Their Pathogenesis

  https://www.mdpi.com/2673-8937/3/4/31

  The increased risk of autoimmune manifestations in patients with CVID/SIgAD has several possible explanations, among which include B and T cell defects, a low rate of isotype-switched B/T memory cells, a reduction in Tregs, the microbiota–immune axis, and molecular mimicry. […] Autoimmune cytopenia represents the majority of autoimmune manifestations of CVID and in 60% of cases, cytopenia precedes hypogammaglobulinemia in the diagnosis of CVID. […] Autoimmune thrombocytopenic purpura is the autoimmune disease most frequently associated with CVID. […] The significant association between enteropathy and liver disease in CVID/SIgAD may be due to the inflammatory response to pathogens delivered from the leaky gut to the liver through the portal vein, or due to a different common pathophysiological basis resulting in T cell-mediated liver damage.

• #79 Common Variable Immunodeficiency and Selective IgA Deficiency: Focus on Autoimmune Manifestations and Their Pathogenesis

  https://www.mdpi.com/2673-8937/3/4/31

  The increased risk of autoimmune manifestations in patients with CVID/SIgAD has several possible explanations, among which include B and T cell defects, a low rate of isotype-switched B/T memory cells, a reduction in Tregs, the microbiota–immune axis, and molecular mimicry. […] Autoimmune cytopenia represents the majority of autoimmune manifestations of CVID and in 60% of cases, cytopenia precedes hypogammaglobulinemia in the diagnosis of CVID. […] Autoimmune thrombocytopenic purpura is the autoimmune disease most frequently associated with CVID. […] The significant association between enteropathy and liver disease in CVID/SIgAD may be due to the inflammatory response to pathogens delivered from the leaky gut to the liver through the portal vein, or due to a different common pathophysiological basis resulting in T cell-mediated liver damage.

• #80 Common variable immunodeficiency and autoimmune diseases: A 10-year single-center experience | Volume 39 – Issue 4 – December 2024 | Archives of Rheumatology

  https://www.archivesofrheumatology.org/full-text/1626

  The pathogenic mechanism of autoimmunity in CVID is paradoxical. It has been suggested that the underlying cause of autoimmunity is based on the inability of these patients to eliminate microbial antigens, leading to alternative immune pathways and an excessive and chronic inflammatory response, damaging not only infected cells but also the surrounding tissue. It is also thought that the high antigen load caused by recurrent or resistant infections causes autoimmunity by affecting tolerance through superantigens or molecular mimicry. Although the mechanisms of ADs are still controversial, they likely involve central and peripheral tolerance disorders and defects in autoreactive T and B cells. In CVID, defects in B cell maturation, CD21low B cells, and cSMB cell development can be encountered. As a result, the proportion of total B cells and cSMB cells is reduced. […] Low cSMB cell levels were reported to be an independent risk factor in predicting AD, granulomatous findings, and splenomegaly. Therefore, it may be used as a guide in the routine evaluation and follow-up of CVID and other B cell-derived diseases.

• #81 Common Variable Immunodeficiency and Selective IgA Deficiency: Focus on Autoimmune Manifestations and Their Pathogenesis

  https://www.mdpi.com/2673-8937/3/4/31

  The increased risk of autoimmune manifestations in patients with CVID/SIgAD has several possible explanations, among which include B and T cell defects, a low rate of isotype-switched B/T memory cells, a reduction in Tregs, the microbiota–immune axis, and molecular mimicry. […] Autoimmune cytopenia represents the majority of autoimmune manifestations of CVID and in 60% of cases, cytopenia precedes hypogammaglobulinemia in the diagnosis of CVID. […] Autoimmune thrombocytopenic purpura is the autoimmune disease most frequently associated with CVID. […] The significant association between enteropathy and liver disease in CVID/SIgAD may be due to the inflammatory response to pathogens delivered from the leaky gut to the liver through the portal vein, or due to a different common pathophysiological basis resulting in T cell-mediated liver damage.

• #82 Common Variable Immunodeficiency and Selective IgA Deficiency: Focus on Autoimmune Manifestations and Their Pathogenesis

  https://www.mdpi.com/2673-8937/3/4/31

  The increased risk of autoimmune manifestations in patients with CVID/SIgAD has several possible explanations, among which include B and T cell defects, a low rate of isotype-switched B/T memory cells, a reduction in Tregs, the microbiota–immune axis, and molecular mimicry. […] Autoimmune cytopenia represents the majority of autoimmune manifestations of CVID and in 60% of cases, cytopenia precedes hypogammaglobulinemia in the diagnosis of CVID. […] Autoimmune thrombocytopenic purpura is the autoimmune disease most frequently associated with CVID. […] The significant association between enteropathy and liver disease in CVID/SIgAD may be due to the inflammatory response to pathogens delivered from the leaky gut to the liver through the portal vein, or due to a different common pathophysiological basis resulting in T cell-mediated liver damage.

• #83 What Is Common Variable Immunodeficiency (CVID)?

  https://www.webmd.com/a-to-z-guides/what-is-common-variable-immunodeficiency-cvid

  Common variable immunodeficiency (CVID) is a type of genetic condition called primary immunodeficiency disease (PIDD) that causes low levels of antibodies (protective proteins) in your body. This weakens your immune system the mechanism that helps your body fight off germs and prevent infections. […] You can also get CVID if you have genetic defects in your immune system. This means there might be added or missing information in your DNA. The defects can cause your immune system to produce very low levels of antibodies in your blood called immunoglobulins and immunoglobulin G (IgG) the proteins that help your body fight infections. […] When your immune system doesnt function as it should, youre more likely to have serious, sometimes life-threatening conditions than people who don’t have CVID. […] About 1 in 4 people with CVID tend to get an autoimmune condition. […] CVID increases your risk for specific cancers like lymphoma or stomach cancer.

• #84 Epidemiology and pathophysiology of malignancy in common variable immunodeficiency? | Allergologia et Immunopathologia

  https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-epidemiology-pathophysiology-malignancy-in-common-S030105461730037X

  Common variable immunodeficiency (CVID) is a diagnostic category of primary immunodeficiency (PID) which may present with heterogeneous disorders including recurrent infections, autoimmunity, granulomatous diseases, lymphoid and other types of malignancies. […] The exact pathological mechanisms for cancer development in CVID are not fully determined; however, several mechanisms including impaired genetic stability, genetic predisposition, immune dysregulation, impaired clearance of oncogenic viruses and bacterial infections, and iatrogenic causes have been proposed to contribute to the high susceptibility of these patients to malignancies. […] The exact pathological mechanisms of malignancy in CVID are not fully determined; although several mechanisms have been suggested to contribute to the high susceptibility of these patients to specific types of malignancies.

• #85 Epidemiology and pathophysiology of malignancy in common variable immunodeficiency? | Allergologia et Immunopathologia

  https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-epidemiology-pathophysiology-malignancy-in-common-S030105461730037X

  These mechanisms include innate genetic instability and genetic predisposition, persistent activation and proliferation of the lymphoid cells during the course of infections, impaired clearance of oncogenic viruses and bacterial infections. […] Impaired immune response results in decreased clearance of oncogenic viruses and bacteria, as well as chronic antigen stimulation, chronic inflammatory response, and survival and proliferation of premalignant and malignant cells, all of which can predispose CVID patients to oncogenic mutations and malignant transformations. […] The proposed mechanism includes genetics, radiosensitivity, immune dysregulation, and chronic infections such as Helicobacter pylori, Epstein-Barr virus (EBV), human herpes virus type 8 (HHV8) and cytomegalovirus (CMV). […] Genetic predisposition to some types of malignancies is a probable aetiology of cancer in some PID patients, although not usually as a result of oncogenic genes.

• #86 Epidemiology and pathophysiology of malignancy in common variable immunodeficiency? | Allergologia et Immunopathologia

  https://www.elsevier.es/es-revista-allergologia-et-immunopathologia-105-articulo-epidemiology-pathophysiology-malignancy-in-common-S030105461730037X

  These mechanisms include innate genetic instability and genetic predisposition, persistent activation and proliferation of the lymphoid cells during the course of infections, impaired clearance of oncogenic viruses and bacterial infections. […] Impaired immune response results in decreased clearance of oncogenic viruses and bacteria, as well as chronic antigen stimulation, chronic inflammatory response, and survival and proliferation of premalignant and malignant cells, all of which can predispose CVID patients to oncogenic mutations and malignant transformations. […] There are multiple associations between a broad spectrum of autoimmune diseases, chronic inflammatory diseases, and cancer development. […] Infections with certain type of viruses and bacteria have been recognised as risk factors for several types of cancer in different ways; when some viruses directly affect the genes inside cells and cause them to grow out of control, other infectious organisms can cause long-term inflammation which leads to changes in the infected cells and in nearby immune cells, and eventually lead to cancer. […] A genetic predisposition to some types of malignancies is a probable aetiology of cancer in some PID patients, although not usually as a result of oncogenic genes. […] The higher incidence of cancer in CVID cases has also been explained by genomic instability.

• #87 Epidemiology and pathophysiology of malignancy in common variable immunodeficiency? | Allergologia et Immunopathologia

  https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-epidemiology-pathophysiology-malignancy-in-common-S030105461730037X

  These mechanisms include innate genetic instability and genetic predisposition, persistent activation and proliferation of the lymphoid cells during the course of infections, impaired clearance of oncogenic viruses and bacterial infections. […] Impaired immune response results in decreased clearance of oncogenic viruses and bacteria, as well as chronic antigen stimulation, chronic inflammatory response, and survival and proliferation of premalignant and malignant cells, all of which can predispose CVID patients to oncogenic mutations and malignant transformations. […] The proposed mechanism includes genetics, radiosensitivity, immune dysregulation, and chronic infections such as Helicobacter pylori, Epstein-Barr virus (EBV), human herpes virus type 8 (HHV8) and cytomegalovirus (CMV). […] Genetic predisposition to some types of malignancies is a probable aetiology of cancer in some PID patients, although not usually as a result of oncogenic genes.

• #88 Epidemiology and pathophysiology of malignancy in common variable immunodeficiency? | Allergologia et Immunopathologia

  https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-epidemiology-pathophysiology-malignancy-in-common-S030105461730037X

  These mechanisms include innate genetic instability and genetic predisposition, persistent activation and proliferation of the lymphoid cells during the course of infections, impaired clearance of oncogenic viruses and bacterial infections. […] Impaired immune response results in decreased clearance of oncogenic viruses and bacteria, as well as chronic antigen stimulation, chronic inflammatory response, and survival and proliferation of premalignant and malignant cells, all of which can predispose CVID patients to oncogenic mutations and malignant transformations. […] The proposed mechanism includes genetics, radiosensitivity, immune dysregulation, and chronic infections such as Helicobacter pylori, Epstein-Barr virus (EBV), human herpes virus type 8 (HHV8) and cytomegalovirus (CMV). […] Genetic predisposition to some types of malignancies is a probable aetiology of cancer in some PID patients, although not usually as a result of oncogenic genes.

• #89 Epidemiology and pathophysiology of malignancy in common variable immunodeficiency? | Allergologia et Immunopathologia

  https://www.elsevier.es/es-revista-allergologia-et-immunopathologia-105-articulo-epidemiology-pathophysiology-malignancy-in-common-S030105461730037X

  These mechanisms include innate genetic instability and genetic predisposition, persistent activation and proliferation of the lymphoid cells during the course of infections, impaired clearance of oncogenic viruses and bacterial infections. […] Impaired immune response results in decreased clearance of oncogenic viruses and bacteria, as well as chronic antigen stimulation, chronic inflammatory response, and survival and proliferation of premalignant and malignant cells, all of which can predispose CVID patients to oncogenic mutations and malignant transformations. […] There are multiple associations between a broad spectrum of autoimmune diseases, chronic inflammatory diseases, and cancer development. […] Infections with certain type of viruses and bacteria have been recognised as risk factors for several types of cancer in different ways; when some viruses directly affect the genes inside cells and cause them to grow out of control, other infectious organisms can cause long-term inflammation which leads to changes in the infected cells and in nearby immune cells, and eventually lead to cancer. […] A genetic predisposition to some types of malignancies is a probable aetiology of cancer in some PID patients, although not usually as a result of oncogenic genes. […] The higher incidence of cancer in CVID cases has also been explained by genomic instability.

• #90 Epidemiology and pathophysiology of malignancy in common variable immunodeficiency? | Allergologia et Immunopathologia

  https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-epidemiology-pathophysiology-malignancy-in-common-S030105461730037X

  These mechanisms include innate genetic instability and genetic predisposition, persistent activation and proliferation of the lymphoid cells during the course of infections, impaired clearance of oncogenic viruses and bacterial infections. […] Impaired immune response results in decreased clearance of oncogenic viruses and bacteria, as well as chronic antigen stimulation, chronic inflammatory response, and survival and proliferation of premalignant and malignant cells, all of which can predispose CVID patients to oncogenic mutations and malignant transformations. […] The proposed mechanism includes genetics, radiosensitivity, immune dysregulation, and chronic infections such as Helicobacter pylori, Epstein-Barr virus (EBV), human herpes virus type 8 (HHV8) and cytomegalovirus (CMV). […] Genetic predisposition to some types of malignancies is a probable aetiology of cancer in some PID patients, although not usually as a result of oncogenic genes.

• #91 Epidemiology and pathophysiology of malignancy in common variable immunodeficiency? | Allergologia et Immunopathologia

  https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-epidemiology-pathophysiology-malignancy-in-common-S030105461730037X

  The higher incidence of cancer in CVID cases has also been explained by genomic instability. […] The impact of these findings could be greatly improved by identifying the underlying genetic cause of radiation sensitivity in CVID patients. […] Altogether, defective repair of AID-induced mutations with reports of increased chromosomal radiation sensitivity and associated lymphoproliferative disorders in CVID patients, suggest that altered DNA damage repair may be a cause of malignancy in CVID.

• #92 Epidemiology and pathophysiology of malignancy in common variable immunodeficiency? | Allergologia et Immunopathologia

  https://www.elsevier.es/es-revista-allergologia-et-immunopathologia-105-articulo-epidemiology-pathophysiology-malignancy-in-common-S030105461730037X

  These mechanisms include innate genetic instability and genetic predisposition, persistent activation and proliferation of the lymphoid cells during the course of infections, impaired clearance of oncogenic viruses and bacterial infections. […] Impaired immune response results in decreased clearance of oncogenic viruses and bacteria, as well as chronic antigen stimulation, chronic inflammatory response, and survival and proliferation of premalignant and malignant cells, all of which can predispose CVID patients to oncogenic mutations and malignant transformations. […] There are multiple associations between a broad spectrum of autoimmune diseases, chronic inflammatory diseases, and cancer development. […] Infections with certain type of viruses and bacteria have been recognised as risk factors for several types of cancer in different ways; when some viruses directly affect the genes inside cells and cause them to grow out of control, other infectious organisms can cause long-term inflammation which leads to changes in the infected cells and in nearby immune cells, and eventually lead to cancer. […] A genetic predisposition to some types of malignancies is a probable aetiology of cancer in some PID patients, although not usually as a result of oncogenic genes. […] The higher incidence of cancer in CVID cases has also been explained by genomic instability.

• #93 Epidemiology and pathophysiology of malignancy in common variable immunodeficiency? | Allergologia et Immunopathologia

  https://www.elsevier.es/es-revista-allergologia-et-immunopathologia-105-articulo-epidemiology-pathophysiology-malignancy-in-common-S030105461730037X

  These mechanisms include innate genetic instability and genetic predisposition, persistent activation and proliferation of the lymphoid cells during the course of infections, impaired clearance of oncogenic viruses and bacterial infections. […] Impaired immune response results in decreased clearance of oncogenic viruses and bacteria, as well as chronic antigen stimulation, chronic inflammatory response, and survival and proliferation of premalignant and malignant cells, all of which can predispose CVID patients to oncogenic mutations and malignant transformations. […] There are multiple associations between a broad spectrum of autoimmune diseases, chronic inflammatory diseases, and cancer development. […] Infections with certain type of viruses and bacteria have been recognised as risk factors for several types of cancer in different ways; when some viruses directly affect the genes inside cells and cause them to grow out of control, other infectious organisms can cause long-term inflammation which leads to changes in the infected cells and in nearby immune cells, and eventually lead to cancer. […] A genetic predisposition to some types of malignancies is a probable aetiology of cancer in some PID patients, although not usually as a result of oncogenic genes. […] The higher incidence of cancer in CVID cases has also been explained by genomic instability.

• #94 Common Variable Immunodeficiency and Selective IgA Deficiency: Focus on Autoimmune Manifestations and Their Pathogenesis

  https://www.mdpi.com/2673-8937/3/4/31

  Autoimmunity is more prevalent in primary humoral immunodeficiencies than in most other IEI and it can even be their first manifestation. […] Among these, the two most common primary immunodeficiencies are selective IgA deficiency and common variable immunodeficiency. […] Complex alterations of the central and peripheral mechanisms of tolerance are involved, affecting mainly B lymphocytes but also T cells and cytokines. […] Not only the immunophenotype but also advances in genetics allow us to diagnose monogenic variants of these diseases and to investigate the pathogenetic basis of the immune dysregulation. […] CVID is a complex syndrome which probably comprises a variety of different diseases with different pathogenetic mechanisms, all leading to hypogammaglobulinemia of IgG and at least another antibody class, and current understanding of its pathophysiology remains still incomplete.

• #95 Common Variable Immunodeficiency and Selective IgA Deficiency: Focus on Autoimmune Manifestations and Their Pathogenesis

  https://www.mdpi.com/2673-8937/3/4/31

  The pathophysiology of CVID is rather mysterious, despite the progress in molecular biology, immunophenotyping, and genetics. […] The peripheral selection of memory B cells appears to be impaired in CVID with an autoimmune phenotype: a low number of switched memory B cells and CD27+, based on total blood lymphocytes, is an independent risk factor for autoimmune disease, granuloma formation, and splenomegaly. […] TACI and BAFF-R defects, found in 20–30% of CVID patients, impairing B cell maturation and class-switch recombination of the mature B cell, are associated with variable autoimmune manifestations. […] The coexistence of T and B cell alterations can explain both the hypogammaglobulinemia and the other complications: autoimmunity, lymphoma, inflammation. […] Autoimmunity is the second-most common manifestation both in CVID and in SIgAD, with a prevalence of 30% in CVID and 25–33% in SigAD.

• #96 Common Variable Immunodeficiency and Selective IgA Deficiency: Focus on Autoimmune Manifestations and Their Pathogenesis

  https://www.mdpi.com/2673-8937/3/4/31

  The pathophysiology of CVID is rather mysterious, despite the progress in molecular biology, immunophenotyping, and genetics. […] The peripheral selection of memory B cells appears to be impaired in CVID with an autoimmune phenotype: a low number of switched memory B cells and CD27+, based on total blood lymphocytes, is an independent risk factor for autoimmune disease, granuloma formation, and splenomegaly. […] TACI and BAFF-R defects, found in 20–30% of CVID patients, impairing B cell maturation and class-switch recombination of the mature B cell, are associated with variable autoimmune manifestations. […] The coexistence of T and B cell alterations can explain both the hypogammaglobulinemia and the other complications: autoimmunity, lymphoma, inflammation. […] Autoimmunity is the second-most common manifestation both in CVID and in SIgAD, with a prevalence of 30% in CVID and 25–33% in SigAD.

• #97 Common variable immunodeficiency – Wikipedia

  https://en.wikipedia.org/wiki/Common_variable_immunodeficiency

  There are also T cell abnormalities in CVID including counts, percentages, surface markers and function differences. […] Several recent studies have described a potential role of epigenetics factor (including DNA methylation, chromatin and histone modulation and also non-coding RNAs) in pathogenesis of CVID.

• #98 Common Variable Immunodeficiency (CVID): Cause & Treatment

  https://my.clevelandclinic.org/health/diseases/21143-common-variable-immunodeficiency-cvid

  Common variable immunodeficiency (CVID) is a group of genetic disorders that affect your immune system. People with CVID have low levels of antibodies (proteins that fight infections) in their blood. […] Genetic variations (changes in your DNA, the instructions that make your body work) cause CVID. No single change causes CVID many different gene changes are associated with it and experts think it takes more than one change to cause CVID. The most commonly found mutations are in the TNFRSF13B gene. […] These changes mean that your B-cells a type of immune cell dont work properly. They dont develop into plasma and memory B-cells, which make antibodies (also called immunoglobulins). Specifically, people with CVID have low levels of IgG, IgA and IgM antibodies. […] The gene variations that lead to CVID are inherited in about 10% of cases. Experts dont know what causes them in the other 90% of people with CVID. They think epigenetic changes (changes in the way your body interprets DNA, caused by environmental or lifestyle factors) could contribute to developing CVID. But researchers need more studies to understand this theory better.

• #99 Variable immunodeficiency score upfront analytical link (VISUAL), a proposal for combined prognostic score at diagnosis of common variable immunodeficiency | Scientific Reports

  https://www.nature.com/articles/s41598-021-91791-2

  The broad and heterogeneous clinical spectrum that characterizes common variable immunodeficiency (CVID) is associated with quite different disease course and prognosis, highlighting the need to develop tools that predict complications. […] The clinical phenotyping classification proposed by Chapel, the scoring system to initiate immunoglobulin replacement therapy (IgRT) proposed by Cunningham-Rundles, and the clinical severity scores proposed by Ameratunga and Grimbacher are widely used in clinical practice. […] Here we sought to determine the usefulness of a combined multianalyte CVID prognostic score at diagnosis, namely VISUAL (variable immunodeficiency score by upfront analytical link), to predict prognosis in CVID patients. […] The VISUAL score was developed from the laboratory parameters at CVID diagnosis of each patient, as follows: (i) a list of candidate variables aimed to predict the clinical severity of CVID patients was analyzed (serum immunoglobulins G, A, M and E, IgG subclasses, production of specific antibodies, B lymphocytes, memory B lymphocyte subsets, CD4+ and CD8+ T-lymphocytes, natural killer cells, C3 and C4 complement factors); (ii) only those variables that proved to be statistically significant with p values <0.05 in the multivariable tests (ANOVA) for severity score were included in VISUAL (smB lymphocytes, IgA, specific Ab responses, CD4+ T-lymphocytes); (iii) due to the particular clinical significance of the increase in serum IgM described in previous studies, IgM was considered within the score.

• #100 Variable immunodeficiency score upfront analytical link (VISUAL), a proposal for combined prognostic score at diagnosis of common variable immunodeficiency | Scientific Reports

  https://www.nature.com/articles/s41598-021-91791-2

  The novel VISUAL score, using combined immunological biomarkers at CVID diagnosis, early predicted the severity of clinical manifestations or outcomes in our CVID cohort by two disparate CVID clinical scores, being independent of the course of the disease, with sensitivity of 85% and negative predictive value 77%. […] VISUAL showed superior sensitivity and accuracy to predict severity than the surrogate marker routinely used in clinical practice, namely smB phenotype alone. […] In our series, a large proportion of CVID patients showed severe evolution according to Ameratungas and Grimbachers clinical severity scores (56% and 76%, respectively), maybe reflecting a lack of referral of mild CVID cases in our health areas, which in turn may be associated with delay in diagnosis. […] Indeed, diagnostic delay may condition the development of complications derived from both the disease evolution and the recurrence of associated infections. […] The proposed extended prognostic score proved to be a useful tool to classify CVID patients at diagnosis in order to anticipate and adjust follow-up and management.

• #101 Variable immunodeficiency score upfront analytical link (VISUAL), a proposal for combined prognostic score at diagnosis of common variable immunodeficiency | Scientific Reports

  https://www.nature.com/articles/s41598-021-91791-2

  The novel VISUAL score, using combined immunological biomarkers at CVID diagnosis, early predicted the severity of clinical manifestations or outcomes in our CVID cohort by two disparate CVID clinical scores, being independent of the course of the disease, with sensitivity of 85% and negative predictive value 77%. […] VISUAL showed superior sensitivity and accuracy to predict severity than the surrogate marker routinely used in clinical practice, namely smB phenotype alone. […] In our series, a large proportion of CVID patients showed severe evolution according to Ameratungas and Grimbachers clinical severity scores (56% and 76%, respectively), maybe reflecting a lack of referral of mild CVID cases in our health areas, which in turn may be associated with delay in diagnosis. […] Indeed, diagnostic delay may condition the development of complications derived from both the disease evolution and the recurrence of associated infections. […] The proposed extended prognostic score proved to be a useful tool to classify CVID patients at diagnosis in order to anticipate and adjust follow-up and management.

• #102 Variable immunodeficiency score upfront analytical link (VISUAL), a proposal for combined prognostic score at diagnosis of common variable immunodeficiency | Scientific Reports

  https://www.nature.com/articles/s41598-021-91791-2

  The novel VISUAL score, using combined immunological biomarkers at CVID diagnosis, early predicted the severity of clinical manifestations or outcomes in our CVID cohort by two disparate CVID clinical scores, being independent of the course of the disease, with sensitivity of 85% and negative predictive value 77%. […] VISUAL showed superior sensitivity and accuracy to predict severity than the surrogate marker routinely used in clinical practice, namely smB phenotype alone. […] In our series, a large proportion of CVID patients showed severe evolution according to Ameratungas and Grimbachers clinical severity scores (56% and 76%, respectively), maybe reflecting a lack of referral of mild CVID cases in our health areas, which in turn may be associated with delay in diagnosis. […] Indeed, diagnostic delay may condition the development of complications derived from both the disease evolution and the recurrence of associated infections. […] The proposed extended prognostic score proved to be a useful tool to classify CVID patients at diagnosis in order to anticipate and adjust follow-up and management.

• #103

  https://link.springer.com/article/10.1007/s10875-023-01590-9

  Delayed diagnosis of common variable immunodeficiency (CVID) remains a serious problem. […] We hypothesized that CVID patients would have an increased risk of certain conditions leading to hospital admissions and/or visits in the outpatient department (OPD) compared to the general population and that some of these conditions could act as indicator conditions for a CVID diagnosis. […] A diagnosis in 18 major disease categories showed a significant OR for subsequent diagnosis of CVID. The most substantial association with a subsequent CVID diagnosis was a diagnosis of lower respiratory tract infections (OR: 29.9; 95% CI: 14.263.2) and lung diseases (35.1; 15.082.5). […] Targeted screening for antibody deficiency in patients diagnosed with specific diseases associated with CVID may lead to earlier CVID diagnosis and treatment and thereby potentially reduced morbidity and mortality.

• #104

  https://link.springer.com/article/10.1007/s10875-023-01590-9

  Delayed diagnosis of common variable immunodeficiency (CVID) remains a serious problem. […] We hypothesized that CVID patients would have an increased risk of certain conditions leading to hospital admissions and/or visits in the outpatient department (OPD) compared to the general population and that some of these conditions could act as indicator conditions for a CVID diagnosis. […] A diagnosis in 18 major disease categories showed a significant OR for subsequent diagnosis of CVID. The most substantial association with a subsequent CVID diagnosis was a diagnosis of lower respiratory tract infections (OR: 29.9; 95% CI: 14.263.2) and lung diseases (35.1; 15.082.5). […] Targeted screening for antibody deficiency in patients diagnosed with specific diseases associated with CVID may lead to earlier CVID diagnosis and treatment and thereby potentially reduced morbidity and mortality.

• #105

  https://link.springer.com/article/10.1007/s10875-023-01590-9

  Our findings highlight the importance of screening for hypogammaglobulinemia in individuals presenting with recurrent/severe respiratory infections and/or lung diseases. […] In conclusion, this study suggests the potential for earlier CVID diagnosis by using targeted testing for antibody deficiency in patients diagnosed with CVID indicator conditions.

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