Materiały źródłowe

• #1 Clinical manifestations, epidemiology, and diagnosis of common variable immunodeficiency in adults – UpToDate

  https://www.uptodate.com/contents/clinical-manifestations-epidemiology-and-diagnosis-of-common-variable-immunodeficiency-in-adults

  Clinical manifestations, epidemiology, evaluation, and diagnosis of CVID will be discussed here, with a focus on presentation in adult patients. […] Common variable immunodeficiency (CVID) is an inborn error of immunity (also called primary immunodeficiency) characterized by impaired B cell differentiation with defective immunoglobulin production. […] CVID has been defined by the following laboratory criteria: 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 response to immunizations.

• #2 Making a Diagnosis of Common Variable Immunodeficiency: A Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6973541/

  Common variable immunodeficiency (CVID) is a condition that inhibits the function of the immune system, making those with the condition more susceptible to infection from external pathogens, including bacteria and, less often, viruses. […] Diagnosis remains difficult because the condition mimics other immune conditions and a lack of awareness exists among practicing clinicians. […] Currently, no standardized criteria for the diagnosis of CVID have been established and physician awareness remains low. […] CVID is a diagnosis of exclusion and, therefore, requires specific testing to hone in on a definitive diagnosis. […] One definitive characteristic of CVID is the presence of hypogammaglobulinemia with reduced IgA and, sometimes, concomitant IgM deficiency. […] All secondary causes that may cause low levels of IgG must be excluded before a final diagnosis of CVID is reached.

• #3 Making a Diagnosis of Common Variable Immunodeficiency: A Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6973541/

  Common variable immunodeficiency (CVID) is a condition that inhibits the function of the immune system, making those with the condition more susceptible to infection from external pathogens, including bacteria and, less often, viruses. […] Diagnosis remains difficult because the condition mimics other immune conditions and a lack of awareness exists among practicing clinicians. […] Currently, no standardized criteria for the diagnosis of CVID have been established and physician awareness remains low. […] CVID is a diagnosis of exclusion and, therefore, requires specific testing to hone in on a definitive diagnosis. […] One definitive characteristic of CVID is the presence of hypogammaglobulinemia with reduced IgA and, sometimes, concomitant IgM deficiency. […] All secondary causes that may cause low levels of IgG must be excluded before a final diagnosis of CVID is reached.

• #4 Common Variable Immunodeficiency (CVID): Diagnosis and More

  https://www.verywellhealth.com/common-variable-immunodeficiency-overview-and-more-5202552

  Finally, in the past even experts had disagreed on the diagnostic criteria for CVID, such as whether a poor vaccine response is required to have CVID. […] As a result, diagnosis can be delayed from four to nine years after symptoms begin. […] Therefore, it’s essential to receive a timely, accurate diagnosis if you have symptoms of CVID.

• #5 The burden of common variable immunodeficiency disorders: a retrospective analysis of the European Society for Immunodeficiency (ESID) registry data | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0941-0

  Although a full unanimity regarding the definition of CVID does not exist at this point, a recent International Consensus on Common Variable Immunodeficiency Disorders (ICON) offers a good framework for the diagnosis of CVID. […] Diagnostic delay (median: 4 years) was associated with a higher risk of death: 1.04 (1.02; 1.06) p=0.0003, bronchiectasis: 1.03 (1.01; 1.04) p=0.0001, solid tumor: 1.08 (1.04; 1.11) p.0001 and enteropathy: 1.02 (1.00; 1.05) p=0.0447 and stayed unchanged over four decades (p=0.228). […] Diagnostic delay adjusted for the age at CVID symptoms onset was associated with the prevalence of bronchiectasis: HR (95% CI): 1.03 (1.01; 1.04) p=0.0001, solid tumor: 1.08 (1.04; 1.11) p.0001, and enteropathy: 1.02 (1.00; 1.05) p=0.0447. […] A comparison of three consecutive time periods of CVID diagnosis (1980; 1981-1999; and 2000) revealed no significant difference in diagnostic delay (independent sample Kruskal-Wallis test, p=0.228).

• #6 State-of-the-art diagnostic evaluation of common variable immunodeficiency

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8222108/

  While the diagnosis can be achieved similarly in all CVID patients, those with noninfectious complications have distinct concerns during clinical evaluation. […] State-of-the-art work-up of CVID with noninfectious complications typically includes genetic analysis, which may shape precision therapy, and thoughtful application of postdiagnostic tests that monitor the presence and progression of disease in the myriad of tissues that may be affected. […] Even with recent advancements, knowledge gaps in diagnosis, prognosis, and treatment of CVID persist, and continued research efforts are needed. […] The most recent International Consensus Document (ICON) guidelines list five criteria for CVID diagnosis: (1) IgG level less than 2 standard deviations below age-appropriate references for 2 measurements more than 3 weeks apart unless the level is very low, (2) either a low IgA or IgM, (3) poor antibody responses to vaccination, (4) greater than 4 years of age, (5) no secondary causes of hypogammaglobulinemia.

• #7 State-of-the-art diagnostic evaluation of common variable immunodeficiency

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8222108/

  While the diagnosis can be achieved similarly in all CVID patients, those with noninfectious complications have distinct concerns during clinical evaluation. […] State-of-the-art work-up of CVID with noninfectious complications typically includes genetic analysis, which may shape precision therapy, and thoughtful application of postdiagnostic tests that monitor the presence and progression of disease in the myriad of tissues that may be affected. […] Even with recent advancements, knowledge gaps in diagnosis, prognosis, and treatment of CVID persist, and continued research efforts are needed. […] The most recent International Consensus Document (ICON) guidelines list five criteria for CVID diagnosis: (1) IgG level less than 2 standard deviations below age-appropriate references for 2 measurements more than 3 weeks apart unless the level is very low, (2) either a low IgA or IgM, (3) poor antibody responses to vaccination, (4) greater than 4 years of age, (5) no secondary causes of hypogammaglobulinemia.

• #8 Common Variable Immunodeficiency | Choose the Right Test

  https://arupconsult.com/content/common-variable-immune-deficiency-syndromes

  Common variable immunodeficiency (CVID), the most common clinically significant primary immunodeficiency disease (PID), manifests in children and adults with a wide variability of symptoms and range of severity. CVID is primarily established through laboratory testing of immunoglobulin concentrations, circulating B lymphocytes (B cells), and antibody responses to vaccination. The European Society for Immunodeficiencies (ESID) clinical criteria includes: At least one of the following: increased susceptibility to infection, autoimmune manifestations, granulomatous disease, unexplained polyclonal lymphoproliferation, and/or affected family member(s) with antibody deficiency. Marked decrease of immunoglobulin G (IgG) and IgA with or without low IgM concentration (2 standard deviations of the normal levels for their age) with at least 2 measurements. At least one of the following: poor antibody response to vaccines and/or low numbers of isotype-switched memory B cells. No evidence of profound T-cell deficiency. The ESID requires that a diagnosis of common variable immunodeficiency (CVID) not be made before 4 years of age or before the exclusion of all secondary causes of hypogammaglobulinemia. The majority of individuals with common variable immunodeficiency (CVID) are diagnosed after childhood. Current diagnostic criteria advise caution when considering a diagnosis of CVID in a child younger than 4 years old. Therefore, regular monitoring is imperative to make an expedient diagnosis and ensure that treatment can begin before further damage occurs. Immunoglobulin deficiency can be detected by determining total immunoglobulin G (IgG), IgA, and IgM levels, which is generally the first step in the workup of immunoglobulin disorders, including CVID. A hallmark characteristic of CVID is a marked decrease in IgG concentration, accompanied by reduced IgA and/or IgM concentrations. Abnormal test results should prompt exclusion of other primary (e.g., XLA and X-linked lymphoproliferative disease) and secondary (e.g., medication, bone marrow failure) causes of hypogammaglobulinemia. Immunoglobulin results may appear normal in some individuals with CVID because immunoglobulin levels are not sensitive indicators of specific immunity. For this reason, if a strong suspicion of CVID exists, antibody titers to previously administered vaccines should also be evaluated. Genetic testing for CVID may be considered in cases with an early age of disease onset or with autoimmune or inflammatory complications; in those with other affected family members; and to exclude other immunodeficiencies that arise from known genetic defects, such as hyper-IgM syndrome, which has been found to be associated with defects in the CD40L and CD40 genes.

• #9 Common Variable Immunodeficiency | Choose the Right Test

  https://arupconsult.com/content/common-variable-immune-deficiency-syndromes

  Common variable immunodeficiency (CVID), the most common clinically significant primary immunodeficiency disease (PID), manifests in children and adults with a wide variability of symptoms and range of severity. CVID is primarily established through laboratory testing of immunoglobulin concentrations, circulating B lymphocytes (B cells), and antibody responses to vaccination. The European Society for Immunodeficiencies (ESID) clinical criteria includes: At least one of the following: increased susceptibility to infection, autoimmune manifestations, granulomatous disease, unexplained polyclonal lymphoproliferation, and/or affected family member(s) with antibody deficiency. Marked decrease of immunoglobulin G (IgG) and IgA with or without low IgM concentration (2 standard deviations of the normal levels for their age) with at least 2 measurements. At least one of the following: poor antibody response to vaccines and/or low numbers of isotype-switched memory B cells. No evidence of profound T-cell deficiency. The ESID requires that a diagnosis of common variable immunodeficiency (CVID) not be made before 4 years of age or before the exclusion of all secondary causes of hypogammaglobulinemia. The majority of individuals with common variable immunodeficiency (CVID) are diagnosed after childhood. Current diagnostic criteria advise caution when considering a diagnosis of CVID in a child younger than 4 years old. Therefore, regular monitoring is imperative to make an expedient diagnosis and ensure that treatment can begin before further damage occurs. Immunoglobulin deficiency can be detected by determining total immunoglobulin G (IgG), IgA, and IgM levels, which is generally the first step in the workup of immunoglobulin disorders, including CVID. A hallmark characteristic of CVID is a marked decrease in IgG concentration, accompanied by reduced IgA and/or IgM concentrations. Abnormal test results should prompt exclusion of other primary (e.g., XLA and X-linked lymphoproliferative disease) and secondary (e.g., medication, bone marrow failure) causes of hypogammaglobulinemia. Immunoglobulin results may appear normal in some individuals with CVID because immunoglobulin levels are not sensitive indicators of specific immunity. For this reason, if a strong suspicion of CVID exists, antibody titers to previously administered vaccines should also be evaluated. Genetic testing for CVID may be considered in cases with an early age of disease onset or with autoimmune or inflammatory complications; in those with other affected family members; and to exclude other immunodeficiencies that arise from known genetic defects, such as hyper-IgM syndrome, which has been found to be associated with defects in the CD40L and CD40 genes.

• #10 The diagnosis of common variable immunodeficiency in adults should not be missed: A delayed diagnosis can be devastating | Allergologia et Immunopathologia

  https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-the-diagnosis-common-variable-immunodeficiency-S0301054613001985

  The diagnosis of common variable immunodeficiency in adults should not be missed: A delayed diagnosis can be devastating […] The diagnosis of this disease depends on clinical and laboratory assessments. […] The diagnostic criteria for CVID were introduced by the European Society for Immunodeficiencies (ESID). […] According to these criteria, patients with CVID have a marked decrease of IgG and a marked decrease in at least one of the isotypes IgM or IgA (at least two standard deviations below the mean for age). […] In addition, CVID patients fulfil all of the following criteria: immunodeficiency begins at greater than two years of age, and poor antibody response to vaccines is observed. […] According to ESID criteria, these patients were diagnosed as common variable immunodeficiency (CVID).

• #11 Common Variable Immunodeficiency | Choose the Right Test

  https://arupconsult.com/content/common-variable-immune-deficiency-syndromes

  Common variable immunodeficiency (CVID), the most common clinically significant primary immunodeficiency disease (PID), manifests in children and adults with a wide variability of symptoms and range of severity. CVID is primarily established through laboratory testing of immunoglobulin concentrations, circulating B lymphocytes (B cells), and antibody responses to vaccination. The European Society for Immunodeficiencies (ESID) clinical criteria includes: At least one of the following: increased susceptibility to infection, autoimmune manifestations, granulomatous disease, unexplained polyclonal lymphoproliferation, and/or affected family member(s) with antibody deficiency. Marked decrease of immunoglobulin G (IgG) and IgA with or without low IgM concentration (2 standard deviations of the normal levels for their age) with at least 2 measurements. At least one of the following: poor antibody response to vaccines and/or low numbers of isotype-switched memory B cells. No evidence of profound T-cell deficiency. The ESID requires that a diagnosis of common variable immunodeficiency (CVID) not be made before 4 years of age or before the exclusion of all secondary causes of hypogammaglobulinemia. The majority of individuals with common variable immunodeficiency (CVID) are diagnosed after childhood. Current diagnostic criteria advise caution when considering a diagnosis of CVID in a child younger than 4 years old. Therefore, regular monitoring is imperative to make an expedient diagnosis and ensure that treatment can begin before further damage occurs. Immunoglobulin deficiency can be detected by determining total immunoglobulin G (IgG), IgA, and IgM levels, which is generally the first step in the workup of immunoglobulin disorders, including CVID. A hallmark characteristic of CVID is a marked decrease in IgG concentration, accompanied by reduced IgA and/or IgM concentrations. Abnormal test results should prompt exclusion of other primary (e.g., XLA and X-linked lymphoproliferative disease) and secondary (e.g., medication, bone marrow failure) causes of hypogammaglobulinemia. Immunoglobulin results may appear normal in some individuals with CVID because immunoglobulin levels are not sensitive indicators of specific immunity. For this reason, if a strong suspicion of CVID exists, antibody titers to previously administered vaccines should also be evaluated. Genetic testing for CVID may be considered in cases with an early age of disease onset or with autoimmune or inflammatory complications; in those with other affected family members; and to exclude other immunodeficiencies that arise from known genetic defects, such as hyper-IgM syndrome, which has been found to be associated with defects in the CD40L and CD40 genes.

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

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

  The diagnosis of CVID can only be made after the exclusion of a variety of other causes of hypogammaglobulinemia. […] An inexpensive, quantitative determination of serum immunoglobulins is the first and most important step in the diagnosis of CVID. […] Required for the diagnosis of CVID is the diminution of at least two isotypes (IgG and IgA or IgM). […] While drug-induced hypogammaglobulinemia may be revealed by the patient’s history, proteinuria is detected by Uristix and intestinal protein loss may be suspected from the medical history in combination with a decreased serum albumin concentration. […] Besides quantitative determination of serum immunoglobulins, the basic laboratory tests should include a differential blood count, liver and kidney function parameters and C-reactive protein determination.

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

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

  The diagnosis of CVID can only be made after the exclusion of a variety of other causes of hypogammaglobulinemia. […] An inexpensive, quantitative determination of serum immunoglobulins is the first and most important step in the diagnosis of CVID. […] Required for the diagnosis of CVID is the diminution of at least two isotypes (IgG and IgA or IgM). […] While drug-induced hypogammaglobulinemia may be revealed by the patient’s history, proteinuria is detected by Uristix and intestinal protein loss may be suspected from the medical history in combination with a decreased serum albumin concentration. […] Besides quantitative determination of serum immunoglobulins, the basic laboratory tests should include a differential blood count, liver and kidney function parameters and C-reactive protein determination.

• #14 Common variable immune deficiency disorders – Immunodeficiency UKAccessibilityIncrease TextDecrease TextGrayscaleHigh ContrastNegative ContrastLight BackgroundLinks UnderlineReadable FontReset

  https://www.immunodeficiencyuk.org/common-variable-immune-deficiency-disorders/

  Common features leading to a diagnosis of CVID […] The diagnosis of a CVID is challenging because a doctor needs to exclude other reasons for the failure of antibody production. […] Diagnosis is confirmed by blood tests that check if there are low levels of serum IgG and IgA, and usually IgM. […] A clinical immunologist usually makes the diagnosis of a CVID. […] Lots of different genes may be altered in CVID, and sometimes genetic testing reveals that patients with more severe or unusual forms of a CVID have another related PID, often a combined immunodeficiency. […] The main treatment for a CVID is replacing the missing antibodies using immunoglobulin replacement therapy. […] Not all vaccines are safe to be administered to patients with a CVID and therefore you should discuss any recommended or required vaccinations with your clinical immunology team before receiving a vaccine.

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

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

  CVID should be suspected in children or adults who have a history of recurrent bacterial infections involving ears, sinuses, bronchi, and lungs. The characteristic laboratory features include low levels of serum immunoglobulins, including IgG, often IgA, and sometimes IgM. Another part of the diagnosis of CVID is to determine if there is a lack of functional antibody. This is done by measuring serum levels of antibodies that are specific to vaccine antigens such as Tetanus/Diphtheria, or pneumococcal polysaccharide. People with CVID have very low or absent antibody levels to most of these vaccines. […] Immunization with killed vaccines is used to measure antibody function, and this functional testing is crucial prior to beginning treatment. These tests also help the healthcare providers decide if the individual will benefit from Ig replacement therapy and are often essential in obtaining insurance authorization for this therapy. The number of B and T lymphocytes may also be determined, and their function can be tested in laboratories. Recent studies have also shown that examining the maturity of the B cells in the blood by looking at the surface receptors (B cell memory markers) can help in predicting the relative severity of the immune deficiency.

• #16 State-of-the-art diagnostic evaluation of common variable immunodeficiency

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8222108/

  It is also vital to determine the patients response to vaccines in order to meet diagnostic criteria for CVID. […] Tests that should be considered in CVID patients who present with GI complaints include fecal calprotectin, fecal 1-antitrypsin, and vitamin B12 levels, which has been shown to be low in patients with malabsorption. […] The most recent ICON recommends CVID patients have a chest CT scan and pulmonary function measurement that includes gas transfer, such as diffusion capacity of the lung for carbon monoxide (DLCO), obtained at some time relatively close to the time of diagnosis. […] If hepatic involvement is suspected, a liver function panel may show an elevation in alkaline phosphatase. […] Genetic analysis can be used to shape targeted therapy. […] Genetic testing is potentially useful in CVID, particularly those with noninfectious complications for which it may shape treatment. […] Significant gaps in our knowledge of CVID diagnostic evaluation persist and offer potential to improve identification and management of this primary immunodeficiency if elucidated.

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

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

  The next stage of diagnosis is flow cytometric analysis of lymphocyte subpopulations, including total T, B and natural killer cells, to distinguish late manifesting X-linked agammaglobulinemia and combined immunodeficiencies. […] A bone marrow biopsy should be performed in patients with low B-cell numbers and if lymphoma or myelodysplasia is suspected.

• #18 Common variable immunodeficiency – Wikipedia

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

  According to a European registry study, the mean age at onset of symptoms was 26.3 years old. As per the criteria laid out by ESID (European Society for Immunodeficiencies) and PAGID (Pan-American Group for Immunodeficiency), CVID is diagnosed if: the person presents with a marked decrease in serum IgG levels (4.5 g/L) and a marked decrease below the lower limit of normal for age in at least one of the isotypes IgM or IgA; the person is four years of age or older; the person lacks an antibody immune response to protein antigens or immunization. […] Diagnosis is chiefly by exclusion, i.e., alternative causes of hypogammaglobulinemia, such as X-linked agammaglobulinemia, must be excluded before a diagnosis of CVID can be made. […] Diagnosis is difficult because of the diversity of phenotypes seen in people with CVID. For example, serum immunoglobulin levels in people with CVID vary greatly. Generally, people can be grouped as follows: no immunoglobulin production, immunoglobulin (Ig) M production only, or both normal IgM and IgG production. Additionally, B cell numbers are also highly variable. 12% of people have no detectable B cells, 12% have reduced B cells, and 54% are within the normal range. In general, people with CVID display higher frequencies of naive B cells and lower frequencies of class-switched memory B cells. Frequencies of other B cell populations, such as IgD memory B cells, transitional B cells, and CD21 B cells, are also affected and are associated with specific disease features. Although CVID is often thought of as a serum immunoglobulin- and B cell-mediated disease, T cells can display abnormal behavior. Affected individuals typically present with low frequencies of CD4+, a T-cell marker, and decreased circulation of regulatory T cells and iNKT cells. Notably, approximately 10% of people display CD4+ T cell counts lower than 200 cells/mm3; this particular phenotype of CVID has been named LOCID (Late Onset Combined Immunodeficiency) and has a poorer prognosis than classical CVID.

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

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

  CVID should be suspected in children or adults who have a history of recurrent bacterial infections involving ears, sinuses, bronchi, and lungs. The characteristic laboratory features include low levels of serum immunoglobulins, including IgG, often IgA, and sometimes IgM. Another part of the diagnosis of CVID is to determine if there is a lack of functional antibody. This is done by measuring serum levels of antibodies that are specific to vaccine antigens such as Tetanus/Diphtheria, or pneumococcal polysaccharide. People with CVID have very low or absent antibody levels to most of these vaccines. […] Immunization with killed vaccines is used to measure antibody function, and this functional testing is crucial prior to beginning treatment. These tests also help the healthcare providers decide if the individual will benefit from Ig replacement therapy and are often essential in obtaining insurance authorization for this therapy. The number of B and T lymphocytes may also be determined, and their function can be tested in laboratories. Recent studies have also shown that examining the maturity of the B cells in the blood by looking at the surface receptors (B cell memory markers) can help in predicting the relative severity of the immune deficiency.

• #20 Common Variable Immunodeficiency (CVID) – Immunology; Allergic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/immunology-allergic-disorders/immunodeficiency-disorders/common-variable-immunodeficiency-cvid

  Common variable immunodeficiency (CVID) is characterized by low immunoglobulin (Ig) levels with phenotypically normal B cells that can proliferate but do not develop into Ig-producing cells. Diagnosis is based mainly on serum Ig levels. […] Diagnosis of CVID is suggested by recurrent sinopulmonary infections and requires all of the following: Low (at least 2 standard deviations below the mean) levels of IgG, Low levels of IgA, IgM, or both, Impaired response to immunizations (usually both protein and polysaccharide vaccines), Exclusion of other immunodeficiency disorders. […] B-cell and T-cell quantification by flow cytometry is done to exclude other immunodeficiency disorders and to distinguish CVID from X-linked agammaglobulinemia, multiple myeloma, and chronic lymphocytic leukemia; findings may include low numbers of class-switched memory B cells or CD21+ cells.

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

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

  Common variable immunodeficiency (CVID) is a disorder that involves the following: Low levels of most or all of the immunoglobulin (Ig) classes. A diagnosis of CVID is reserved for persons with an undefined B-cell dysfunction. […] In patients with CVID, laboratory studies can reveal the following: Serum IgA and IgG levels – Decreased (not absent). Serum IgM levels – Decreased (occasionally). Circulating T and B lymphocytes – Can be assessed by using monoclonal antibodies for immunofluorescence staining. T-cell function – In vivo measurement is possible by using an anergy panel to assess localized immunologic skin responses. […] In patients with CVID, high-resolution CT scanning of the chest may be more useful than plain chest radiography or pulmonary function testing in detecting pulmonary abnormalities.

• #22 Common Variable Immunodeficiency Workup: Laboratory Studies, Imaging Studies, Other Tests

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

  A positive test result indicates intact delayed-type hypersensitivity. A negative test result to all antigens suggests impaired type IV immunity. […] To assess the functional activity of the lymphocytes in vitro, they must be isolated and stimulated with a variety of agents. […] T-cell activity can be directly studied. T lymphocytes express certain antigens after activation. […] Measuring the levels of mediators and cytokines such as IL-2, IL-4, IL-5, interleukin 6 (IL-6), interferon gamma, and tumor necrosis factor in the culture supernatant is another useful tool. […] The complete blood count and autoantibody testing may be helpful as well. Anemia secondary to an autoimmune process may be detected. Severe lymphopenia may indicate that the patient has severe combined immunodeficiency disease or other primary T-cell defects.

• #23 Common Variable Immunodeficiency (CVID) – Immunology; Allergic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/immunology-allergic-disorders/immunodeficiency-disorders/common-variable-immunodeficiency-cvid

  Serum protein electrophoresis is done to screen for monoclonal gammopathies (eg, myeloma), which may be associated with reduced levels of other immunoglobulin isotypes. […] Because mutations are usually sporadic, screening relatives is not recommended unless there is a significant family history of CVID.

• #24 Making a Diagnosis of Common Variable Immunodeficiency: A Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6973541/

  Furthermore, patients with large T-cell deficiencies must also be ruled out before making the diagnosis. […] CVID is associated with some platelet disorders, such as granulocytopenia, lymphocytopenia, small platelets, and thrombocytopenia, so a complete blood count (CBC) with differential would be helpful. […] Immunoglobulin levels can also rule in or out other diseases, such as hyper IgM syndrome. […] Measuring immunoglobulin levels before and after vaccinations is another diagnostic tool, as noted above, impaired vaccine response can also suggest CVID. […] In some patients, CVID can manifest with granulomas in the lungs, lymph nodes, liver, and other organs. […] This can progress to granulomatous lymphocytic interstitial lung disease (GLILD), which can be difficult to detect. […] In a study by Jolles et al., fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) was shown to significantly aid in detecting and monitoring GLILD in CVID patients. […] The diagnosis of this condition is usually done through a process of elimination and treatment is based on presenting symptomatology and organ system affected.

• #25 Common Variable Immunodeficiency | Choose the Right Test

  https://arupconsult.com/content/common-variable-immune-deficiency-syndromes

  Common variable immunodeficiency (CVID), the most common clinically significant primary immunodeficiency disease (PID), manifests in children and adults with a wide variability of symptoms and range of severity. CVID is primarily established through laboratory testing of immunoglobulin concentrations, circulating B lymphocytes (B cells), and antibody responses to vaccination. The European Society for Immunodeficiencies (ESID) clinical criteria includes: At least one of the following: increased susceptibility to infection, autoimmune manifestations, granulomatous disease, unexplained polyclonal lymphoproliferation, and/or affected family member(s) with antibody deficiency. Marked decrease of immunoglobulin G (IgG) and IgA with or without low IgM concentration (2 standard deviations of the normal levels for their age) with at least 2 measurements. At least one of the following: poor antibody response to vaccines and/or low numbers of isotype-switched memory B cells. No evidence of profound T-cell deficiency. The ESID requires that a diagnosis of common variable immunodeficiency (CVID) not be made before 4 years of age or before the exclusion of all secondary causes of hypogammaglobulinemia. The majority of individuals with common variable immunodeficiency (CVID) are diagnosed after childhood. Current diagnostic criteria advise caution when considering a diagnosis of CVID in a child younger than 4 years old. Therefore, regular monitoring is imperative to make an expedient diagnosis and ensure that treatment can begin before further damage occurs. Immunoglobulin deficiency can be detected by determining total immunoglobulin G (IgG), IgA, and IgM levels, which is generally the first step in the workup of immunoglobulin disorders, including CVID. A hallmark characteristic of CVID is a marked decrease in IgG concentration, accompanied by reduced IgA and/or IgM concentrations. Abnormal test results should prompt exclusion of other primary (e.g., XLA and X-linked lymphoproliferative disease) and secondary (e.g., medication, bone marrow failure) causes of hypogammaglobulinemia. Immunoglobulin results may appear normal in some individuals with CVID because immunoglobulin levels are not sensitive indicators of specific immunity. For this reason, if a strong suspicion of CVID exists, antibody titers to previously administered vaccines should also be evaluated. Genetic testing for CVID may be considered in cases with an early age of disease onset or with autoimmune or inflammatory complications; in those with other affected family members; and to exclude other immunodeficiencies that arise from known genetic defects, such as hyper-IgM syndrome, which has been found to be associated with defects in the CD40L and CD40 genes.

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

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

  The diagnosis of CVID can only be made after the exclusion of a variety of other causes of hypogammaglobulinemia. […] An inexpensive, quantitative determination of serum immunoglobulins is the first and most important step in the diagnosis of CVID. […] Required for the diagnosis of CVID is the diminution of at least two isotypes (IgG and IgA or IgM). […] While drug-induced hypogammaglobulinemia may be revealed by the patient’s history, proteinuria is detected by Uristix and intestinal protein loss may be suspected from the medical history in combination with a decreased serum albumin concentration. […] Besides quantitative determination of serum immunoglobulins, the basic laboratory tests should include a differential blood count, liver and kidney function parameters and C-reactive protein determination.

• #27 State-of-the-art diagnostic evaluation of common variable immunodeficiency

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8222108/

  It is also vital to determine the patients response to vaccines in order to meet diagnostic criteria for CVID. […] Tests that should be considered in CVID patients who present with GI complaints include fecal calprotectin, fecal 1-antitrypsin, and vitamin B12 levels, which has been shown to be low in patients with malabsorption. […] The most recent ICON recommends CVID patients have a chest CT scan and pulmonary function measurement that includes gas transfer, such as diffusion capacity of the lung for carbon monoxide (DLCO), obtained at some time relatively close to the time of diagnosis. […] If hepatic involvement is suspected, a liver function panel may show an elevation in alkaline phosphatase. […] Genetic analysis can be used to shape targeted therapy. […] Genetic testing is potentially useful in CVID, particularly those with noninfectious complications for which it may shape treatment. […] Significant gaps in our knowledge of CVID diagnostic evaluation persist and offer potential to improve identification and management of this primary immunodeficiency if elucidated.

• #28 Common Variable Immunodeficiency Workup: Laboratory Studies, Imaging Studies, Other Tests

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

  For the detection of pulmonary abnormalities in patients with common variable immunodeficiency (CVID), high-resolution computed tomography of the chest may be more useful than plain chest radiography or pulmonary function testing. […] Excluding an infectious etiology is important. The periodic monitoring of pulmonary function is crucial in any patient who is able to perform the forced expiratory maneuvers. […] Biopsy should be considered to exclude infection or malignancy in enlarging lymph nodes. […] Histologic changes may be observed in the lymph nodes of patients with CVID. The findings may include reactive follicular hyperplasia, atypical hyperplasia, and granulomatous inflammation. […] Any malignancies complicating CVID are staged by using conventional guidelines.

• #29 State-of-the-art diagnostic evaluation of common variable immunodeficiency

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8222108/

  It is also vital to determine the patients response to vaccines in order to meet diagnostic criteria for CVID. […] Tests that should be considered in CVID patients who present with GI complaints include fecal calprotectin, fecal 1-antitrypsin, and vitamin B12 levels, which has been shown to be low in patients with malabsorption. […] The most recent ICON recommends CVID patients have a chest CT scan and pulmonary function measurement that includes gas transfer, such as diffusion capacity of the lung for carbon monoxide (DLCO), obtained at some time relatively close to the time of diagnosis. […] If hepatic involvement is suspected, a liver function panel may show an elevation in alkaline phosphatase. […] Genetic analysis can be used to shape targeted therapy. […] Genetic testing is potentially useful in CVID, particularly those with noninfectious complications for which it may shape treatment. […] Significant gaps in our knowledge of CVID diagnostic evaluation persist and offer potential to improve identification and management of this primary immunodeficiency if elucidated.

• #30 State-of-the-art diagnostic evaluation of common variable immunodeficiency

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8222108/

  It is also vital to determine the patients response to vaccines in order to meet diagnostic criteria for CVID. […] Tests that should be considered in CVID patients who present with GI complaints include fecal calprotectin, fecal 1-antitrypsin, and vitamin B12 levels, which has been shown to be low in patients with malabsorption. […] The most recent ICON recommends CVID patients have a chest CT scan and pulmonary function measurement that includes gas transfer, such as diffusion capacity of the lung for carbon monoxide (DLCO), obtained at some time relatively close to the time of diagnosis. […] If hepatic involvement is suspected, a liver function panel may show an elevation in alkaline phosphatase. […] Genetic analysis can be used to shape targeted therapy. […] Genetic testing is potentially useful in CVID, particularly those with noninfectious complications for which it may shape treatment. […] Significant gaps in our knowledge of CVID diagnostic evaluation persist and offer potential to improve identification and management of this primary immunodeficiency if elucidated.

• #31 Making a Diagnosis of Common Variable Immunodeficiency: A Review

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6973541/

  Furthermore, patients with large T-cell deficiencies must also be ruled out before making the diagnosis. […] CVID is associated with some platelet disorders, such as granulocytopenia, lymphocytopenia, small platelets, and thrombocytopenia, so a complete blood count (CBC) with differential would be helpful. […] Immunoglobulin levels can also rule in or out other diseases, such as hyper IgM syndrome. […] Measuring immunoglobulin levels before and after vaccinations is another diagnostic tool, as noted above, impaired vaccine response can also suggest CVID. […] In some patients, CVID can manifest with granulomas in the lungs, lymph nodes, liver, and other organs. […] This can progress to granulomatous lymphocytic interstitial lung disease (GLILD), which can be difficult to detect. […] In a study by Jolles et al., fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) was shown to significantly aid in detecting and monitoring GLILD in CVID patients. […] The diagnosis of this condition is usually done through a process of elimination and treatment is based on presenting symptomatology and organ system affected.

• #32 Common Variable Immunodeficiency Workup: Laboratory Studies, Imaging Studies, Other Tests

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

  For the detection of pulmonary abnormalities in patients with common variable immunodeficiency (CVID), high-resolution computed tomography of the chest may be more useful than plain chest radiography or pulmonary function testing. […] Excluding an infectious etiology is important. The periodic monitoring of pulmonary function is crucial in any patient who is able to perform the forced expiratory maneuvers. […] Biopsy should be considered to exclude infection or malignancy in enlarging lymph nodes. […] Histologic changes may be observed in the lymph nodes of patients with CVID. The findings may include reactive follicular hyperplasia, atypical hyperplasia, and granulomatous inflammation. […] Any malignancies complicating CVID are staged by using conventional guidelines.

• #33 State-of-the-art diagnostic evaluation of common variable immunodeficiency

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8222108/

  It is also vital to determine the patients response to vaccines in order to meet diagnostic criteria for CVID. […] Tests that should be considered in CVID patients who present with GI complaints include fecal calprotectin, fecal 1-antitrypsin, and vitamin B12 levels, which has been shown to be low in patients with malabsorption. […] The most recent ICON recommends CVID patients have a chest CT scan and pulmonary function measurement that includes gas transfer, such as diffusion capacity of the lung for carbon monoxide (DLCO), obtained at some time relatively close to the time of diagnosis. […] If hepatic involvement is suspected, a liver function panel may show an elevation in alkaline phosphatase. […] Genetic analysis can be used to shape targeted therapy. […] Genetic testing is potentially useful in CVID, particularly those with noninfectious complications for which it may shape treatment. […] Significant gaps in our knowledge of CVID diagnostic evaluation persist and offer potential to improve identification and management of this primary immunodeficiency if elucidated.

• #34 State-of-the-art diagnostic evaluation of common variable immunodeficiency

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8222108/

  It is also vital to determine the patients response to vaccines in order to meet diagnostic criteria for CVID. […] Tests that should be considered in CVID patients who present with GI complaints include fecal calprotectin, fecal 1-antitrypsin, and vitamin B12 levels, which has been shown to be low in patients with malabsorption. […] The most recent ICON recommends CVID patients have a chest CT scan and pulmonary function measurement that includes gas transfer, such as diffusion capacity of the lung for carbon monoxide (DLCO), obtained at some time relatively close to the time of diagnosis. […] If hepatic involvement is suspected, a liver function panel may show an elevation in alkaline phosphatase. […] Genetic analysis can be used to shape targeted therapy. […] Genetic testing is potentially useful in CVID, particularly those with noninfectious complications for which it may shape treatment. […] Significant gaps in our knowledge of CVID diagnostic evaluation persist and offer potential to improve identification and management of this primary immunodeficiency if elucidated.

• #35 State-of-the-art diagnostic evaluation of common variable immunodeficiency

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8222108/

  It is also vital to determine the patients response to vaccines in order to meet diagnostic criteria for CVID. […] Tests that should be considered in CVID patients who present with GI complaints include fecal calprotectin, fecal 1-antitrypsin, and vitamin B12 levels, which has been shown to be low in patients with malabsorption. […] The most recent ICON recommends CVID patients have a chest CT scan and pulmonary function measurement that includes gas transfer, such as diffusion capacity of the lung for carbon monoxide (DLCO), obtained at some time relatively close to the time of diagnosis. […] If hepatic involvement is suspected, a liver function panel may show an elevation in alkaline phosphatase. […] Genetic analysis can be used to shape targeted therapy. […] Genetic testing is potentially useful in CVID, particularly those with noninfectious complications for which it may shape treatment. […] Significant gaps in our knowledge of CVID diagnostic evaluation persist and offer potential to improve identification and management of this primary immunodeficiency if elucidated.

• #36 Genetic testing can narrow CVID diagnosis | Immune Deficiency Foundation

  https://primaryimmune.org/resources/news-articles/genetic-testing-can-narrow-cvid-diagnosis

  Genetic testing can narrow CVID diagnosis. […] As genetic testing technology develops, more patients with CVID and their providers consider its use to pinpoint a more specific diagnosis. […] Dr. Roshini Abraham, a diagnostic immunologist with Nationwide Childrens Hospital, in Columbus, Ohio, recommends patients with CVID pursue genetic testing, despite the relatively low yield in identifying PI-causing gene variants. Identifying the specific genetic variant through genetic testing, when a positive result is obtained, can provide a conclusive diagnosis and inform treatment. […] Being able to put a clear genetic and diagnostic label is very helpful both for the patient and the physician in terms of management. […] Genetic testing can also assist in determining if other members of the family are affected.

• #37 Genes associated with common variable immunodeficiency: one diagnosis to rule them all? | Journal of Medical Genetics

  https://jmg.bmj.com/content/53/9/575

  This review outlines current knowledge on the molecular basis of CVID, covering both monogenic and complex forms, and linking with clinical and immunological phenotypes. […] To date, there are no clinical guidelines regarding the genetic workup of patients presenting with CVID. […] Genetic assessment should at least be considered in patients with severe complications since this may be important to guide treatment and follow-up (eg, LRBA/CTLA-4 deficiency, APDS). […] A monogenic cause of CVID is more likely in case of early disease onset (eg, presenting in infancy or early childhood), a positive family history or consanguinity. […] Overall, the phenotype of CTLA-4 deficiency is reminiscent of that of LRBA deficiency: autoimmunity, recurrent infections, benign lymphoproliferation, and varying Ig levels and B cell and T cell defects. […] It is increasingly believed that besides rare monogenic forms, CVID is a polygenic or multifactorial disorder.

• #38 Genes associated with common variable immunodeficiency: one diagnosis to rule them all? | Journal of Medical Genetics

  https://jmg.bmj.com/content/53/9/575

  This review outlines current knowledge on the molecular basis of CVID, covering both monogenic and complex forms, and linking with clinical and immunological phenotypes. […] To date, there are no clinical guidelines regarding the genetic workup of patients presenting with CVID. […] Genetic assessment should at least be considered in patients with severe complications since this may be important to guide treatment and follow-up (eg, LRBA/CTLA-4 deficiency, APDS). […] A monogenic cause of CVID is more likely in case of early disease onset (eg, presenting in infancy or early childhood), a positive family history or consanguinity. […] Overall, the phenotype of CTLA-4 deficiency is reminiscent of that of LRBA deficiency: autoimmunity, recurrent infections, benign lymphoproliferation, and varying Ig levels and B cell and T cell defects. […] It is increasingly believed that besides rare monogenic forms, CVID is a polygenic or multifactorial disorder.

• #39 Genetic testing can narrow CVID diagnosis | Immune Deficiency Foundation

  https://primaryimmune.org/resources/news-articles/genetic-testing-can-narrow-cvid-diagnosis

  Genetic testing can narrow CVID diagnosis. […] As genetic testing technology develops, more patients with CVID and their providers consider its use to pinpoint a more specific diagnosis. […] Dr. Roshini Abraham, a diagnostic immunologist with Nationwide Childrens Hospital, in Columbus, Ohio, recommends patients with CVID pursue genetic testing, despite the relatively low yield in identifying PI-causing gene variants. Identifying the specific genetic variant through genetic testing, when a positive result is obtained, can provide a conclusive diagnosis and inform treatment. […] Being able to put a clear genetic and diagnostic label is very helpful both for the patient and the physician in terms of management. […] Genetic testing can also assist in determining if other members of the family are affected.

• #40 Genetic testing can narrow CVID diagnosis | Immune Deficiency Foundation

  https://primaryimmune.org/resources/news-articles/genetic-testing-can-narrow-cvid-diagnosis

  The ultimate goal is to improve survival and outcomes. Genetic testing is pretty integral to the diagnosis of rare diseases. […] The three tiers of genetic testing currently available as clinical tests targeted panel testing, exome testing, and genome testing capture different levels of information. […] Through genetic testing, clinicians can identify if there is a genetic cause for CVID symptoms. […] Most doctors start with the targeted genetic panel because its affordable and the data is manageable, particularly if the clinician is not an immunologist or well-versed in genetic testing. […] Proper interpretation of any data, including genetic data, is critical. […] We always recommend appropriate genetic counseling and support. […] Sometimes genetic testing only turns up variants of unknown significance or VUSs.

• #41 Genetic testing can narrow CVID diagnosis | Immune Deficiency Foundation

  https://primaryimmune.org/resources/news-articles/genetic-testing-can-narrow-cvid-diagnosis

  The ultimate goal is to improve survival and outcomes. Genetic testing is pretty integral to the diagnosis of rare diseases. […] The three tiers of genetic testing currently available as clinical tests targeted panel testing, exome testing, and genome testing capture different levels of information. […] Through genetic testing, clinicians can identify if there is a genetic cause for CVID symptoms. […] Most doctors start with the targeted genetic panel because its affordable and the data is manageable, particularly if the clinician is not an immunologist or well-versed in genetic testing. […] Proper interpretation of any data, including genetic data, is critical. […] We always recommend appropriate genetic counseling and support. […] Sometimes genetic testing only turns up variants of unknown significance or VUSs.

• #42 Genes associated with common variable immunodeficiency: one diagnosis to rule them all? | Journal of Medical Genetics

  https://jmg.bmj.com/content/53/9/575

  Common variable immunodeficiency (CVID) is a primary antibody deficiency characterised by hypogammaglobulinaemia, impaired production of specific antibodies after immunisation and increased susceptibility to infections. […] According to the international consensus statement, CVID is defined by a marked decrease in serum IgG, decreased IgM and/or IgA, poor antibody responses to vaccines, and exclusion of defined causes of hypogammaglobulinaemia. […] The majority of CVID cases occur sporadically. […] So far, a monogenic cause has been identified in 2-10% of patients with CVID. […] The past 4 years, next-generation sequencing (NGS) technologies have accelerated the discovery of both autosomal recessive and dominant CVID disease genes. […] In fact, many genes initially reported as CVID disease genes are now considered to be responsible for distinct disease entities.

• #43 Genes associated with common variable immunodeficiency: one diagnosis to rule them all? | Journal of Medical Genetics

  https://jmg.bmj.com/content/53/9/575

  This review outlines current knowledge on the molecular basis of CVID, covering both monogenic and complex forms, and linking with clinical and immunological phenotypes. […] To date, there are no clinical guidelines regarding the genetic workup of patients presenting with CVID. […] Genetic assessment should at least be considered in patients with severe complications since this may be important to guide treatment and follow-up (eg, LRBA/CTLA-4 deficiency, APDS). […] A monogenic cause of CVID is more likely in case of early disease onset (eg, presenting in infancy or early childhood), a positive family history or consanguinity. […] Overall, the phenotype of CTLA-4 deficiency is reminiscent of that of LRBA deficiency: autoimmunity, recurrent infections, benign lymphoproliferation, and varying Ig levels and B cell and T cell defects. […] It is increasingly believed that besides rare monogenic forms, CVID is a polygenic or multifactorial disorder.

• #44 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 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 […] 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. […] 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.

• #45 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 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 […] 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. […] 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.

• #46 New approach to investigate Common Variable Immunodeficiency patients using spectrochemical analysis of blood | Scientific Reports

  https://www.nature.com/articles/s41598-019-43196-5

  Further laboratory testing, such as measuring specific antibodies to vaccine responses, enumeration of lymphocyte subsets (B, T and NK cells) and class-switched memory B cells by flow cytometry, can provide additional evidence to suggest defective antibody production. […] This study has demonstrated the effectiveness of FTIR spectroscopic methods towards the diagnosis of CVID, correctly segregating CVID patients and HC into their respective groups following analysis of biofluids. This has been performed using a classification model on the fingerprint region of the ATR-FTIR spectrum with a sensitivity and specificity of 94% and 95% respectively for plasma, and 97% and 93% respectively for serum. […] The findings from the first stage of this study are encouraging based on the impact that the translation of FTIR spectroscopy into a diagnostic platform for CVID could have on clinical practice.

• #47

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

  Delayed diagnosis of common variable immunodeficiency (CVID) remains a serious problem. We investigated whether some diseases diagnosed during out-patient visits or admission to hospitals could act as indicator conditions for CVID diagnosis. […] A correct and timely diagnosis is challenged by the rare occurrence, the heterogenous presentation, and the lack of knowledge of the disease among non-specialists. […] Delayed CVID diagnosis is a major problem due to the associated increased morbidity and mortality and reduced quality of life. […] This study suggests the potential for earlier CVID diagnosis by using targeted testing for antibody deficiency in patients diagnosed with CVID indicator conditions.

• #48 Common Variable Immunodeficiency – The Rheumatologist

  https://www.the-rheumatologist.org/article/common-variable-immunodeficiency/?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. The rare incidence and high clinical variability of CVID can present a diagnostic challenge. Because there is no specific test for diagnosing CVID, diagnosis is made by excluding similar conditions. The first step is the assessment of the clinical and family history, including a detailed description of the type, duration, and frequency of infections. A systematic assessment of the patients immunological status is the next step. This includes basic laboratory analyses such as a complete blood count, serum immunoglobulin levels (IgG, IgA, and IgM), and total complement levels (CH50). Next, perform a quantitative flow cytometric analysis of lymphocyte phenotypes. Of particular importance is the assessment of specific antibody responses to different antigens (protein and polysaccharide antigens) upon vaccination. Genetic testing and specific in vitro tests (e.g., flow cytometry studies of surface markers and specialized functional testing) are available in immunodeficiency centers and specialized laboratories. However, the identification of the first genetic defects associated with a CVID phenotype mark substantial progress for clinical immunology.

• #49 Common Variable Immunodeficiency – The Rheumatologist

  https://www.the-rheumatologist.org/article/common-variable-immunodeficiency/?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. The rare incidence and high clinical variability of CVID can present a diagnostic challenge. Because there is no specific test for diagnosing CVID, diagnosis is made by excluding similar conditions. The first step is the assessment of the clinical and family history, including a detailed description of the type, duration, and frequency of infections. A systematic assessment of the patients immunological status is the next step. This includes basic laboratory analyses such as a complete blood count, serum immunoglobulin levels (IgG, IgA, and IgM), and total complement levels (CH50). Next, perform a quantitative flow cytometric analysis of lymphocyte phenotypes. Of particular importance is the assessment of specific antibody responses to different antigens (protein and polysaccharide antigens) upon vaccination. Genetic testing and specific in vitro tests (e.g., flow cytometry studies of surface markers and specialized functional testing) are available in immunodeficiency centers and specialized laboratories. However, the identification of the first genetic defects associated with a CVID phenotype mark substantial progress for clinical immunology.

• #50 Common Variable Immunodeficiency – The Rheumatologist

  https://www.the-rheumatologist.org/article/common-variable-immunodeficiency/?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. The rare incidence and high clinical variability of CVID can present a diagnostic challenge. Because there is no specific test for diagnosing CVID, diagnosis is made by excluding similar conditions. The first step is the assessment of the clinical and family history, including a detailed description of the type, duration, and frequency of infections. A systematic assessment of the patients immunological status is the next step. This includes basic laboratory analyses such as a complete blood count, serum immunoglobulin levels (IgG, IgA, and IgM), and total complement levels (CH50). Next, perform a quantitative flow cytometric analysis of lymphocyte phenotypes. Of particular importance is the assessment of specific antibody responses to different antigens (protein and polysaccharide antigens) upon vaccination. Genetic testing and specific in vitro tests (e.g., flow cytometry studies of surface markers and specialized functional testing) are available in immunodeficiency centers and specialized laboratories. However, the identification of the first genetic defects associated with a CVID phenotype mark substantial progress for clinical immunology.

• #51 Common Variable Immunodeficiency – The Rheumatologist

  https://www.the-rheumatologist.org/article/common-variable-immunodeficiency/?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. The rare incidence and high clinical variability of CVID can present a diagnostic challenge. Because there is no specific test for diagnosing CVID, diagnosis is made by excluding similar conditions. The first step is the assessment of the clinical and family history, including a detailed description of the type, duration, and frequency of infections. A systematic assessment of the patients immunological status is the next step. This includes basic laboratory analyses such as a complete blood count, serum immunoglobulin levels (IgG, IgA, and IgM), and total complement levels (CH50). Next, perform a quantitative flow cytometric analysis of lymphocyte phenotypes. Of particular importance is the assessment of specific antibody responses to different antigens (protein and polysaccharide antigens) upon vaccination. Genetic testing and specific in vitro tests (e.g., flow cytometry studies of surface markers and specialized functional testing) are available in immunodeficiency centers and specialized laboratories. However, the identification of the first genetic defects associated with a CVID phenotype mark substantial progress for clinical immunology.

• #52 Common Variable Immunodeficiency – The Rheumatologist

  https://www.the-rheumatologist.org/article/common-variable-immunodeficiency/?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. The rare incidence and high clinical variability of CVID can present a diagnostic challenge. Because there is no specific test for diagnosing CVID, diagnosis is made by excluding similar conditions. The first step is the assessment of the clinical and family history, including a detailed description of the type, duration, and frequency of infections. A systematic assessment of the patients immunological status is the next step. This includes basic laboratory analyses such as a complete blood count, serum immunoglobulin levels (IgG, IgA, and IgM), and total complement levels (CH50). Next, perform a quantitative flow cytometric analysis of lymphocyte phenotypes. Of particular importance is the assessment of specific antibody responses to different antigens (protein and polysaccharide antigens) upon vaccination. Genetic testing and specific in vitro tests (e.g., flow cytometry studies of surface markers and specialized functional testing) are available in immunodeficiency centers and specialized laboratories. However, the identification of the first genetic defects associated with a CVID phenotype mark substantial progress for clinical immunology.

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

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

  CVID should be suspected in children or adults who have a history of recurrent bacterial infections involving ears, sinuses, bronchi, and lungs. The characteristic laboratory features include low levels of serum immunoglobulins, including IgG, often IgA, and sometimes IgM. Another part of the diagnosis of CVID is to determine if there is a lack of functional antibody. This is done by measuring serum levels of antibodies that are specific to vaccine antigens such as Tetanus/Diphtheria, or pneumococcal polysaccharide. People with CVID have very low or absent antibody levels to most of these vaccines. […] Immunization with killed vaccines is used to measure antibody function, and this functional testing is crucial prior to beginning treatment. These tests also help the healthcare providers decide if the individual will benefit from Ig replacement therapy and are often essential in obtaining insurance authorization for this therapy. The number of B and T lymphocytes may also be determined, and their function can be tested in laboratories. Recent studies have also shown that examining the maturity of the B cells in the blood by looking at the surface receptors (B cell memory markers) can help in predicting the relative severity of the immune deficiency.

• #54 Common Variable Immunodeficiency

  https://www.aaaai.org/conditions-treatments/primary-immunodeficiency-disease/common-variable-immunodeficiency

  Common variable immunodeficiency (CVID) is an antibody deficiency that leaves the immune system unable to defend against bacteria and viruses, resulting in recurrent and often severe infections primarily affecting the ears, sinuses, and respiratory tract (sinopulmonary infections). […] In the majority of cases, the diagnosis is not made until the third to fourth decade of life. […] CVID can be diagnosed anytime from childhood through adulthood. […] CVID may be suspected in children or adults with a history of recurrent infections involving the lungs, bronchi, ears or sinuses. […] An accurate diagnosis can be made through screening tests that measure immunoglobulin levels or the number of B cells in the blood. […] CVID is treated with immunoglobulin replacement therapy (IRT), which most often relieves symptoms.

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

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

  CVID should be suspected in children or adults who have a history of recurrent bacterial infections involving ears, sinuses, bronchi, and lungs. The characteristic laboratory features include low levels of serum immunoglobulins, including IgG, often IgA, and sometimes IgM. Another part of the diagnosis of CVID is to determine if there is a lack of functional antibody. This is done by measuring serum levels of antibodies that are specific to vaccine antigens such as Tetanus/Diphtheria, or pneumococcal polysaccharide. People with CVID have very low or absent antibody levels to most of these vaccines. […] Immunization with killed vaccines is used to measure antibody function, and this functional testing is crucial prior to beginning treatment. These tests also help the healthcare providers decide if the individual will benefit from Ig replacement therapy and are often essential in obtaining insurance authorization for this therapy. The number of B and T lymphocytes may also be determined, and their function can be tested in laboratories. Recent studies have also shown that examining the maturity of the B cells in the blood by looking at the surface receptors (B cell memory markers) can help in predicting the relative severity of the immune deficiency.

• #56 Common Variable Immunodeficiency (CVID): Diagnosis and More

  https://www.verywellhealth.com/common-variable-immunodeficiency-overview-and-more-5202552

  After gathering a health history of recurrent infections, CVID can be diagnosed through a series of blood tests. […] To be diagnosed with CVID, a person must have low immunoglobulins (antibodies). This includes low IgG and either IgM or IgA. It also requires a poor response to vaccines and the absence of any other disorder that causes an immunodeficiency. […] Getting diagnosed with CVID can be challenging in multiple ways: A person may become accustomed to their frequent infections and think of them as a fact of life, and subsequently delay seeking medical care. […] As a relatively rare disorder, many health providers do not know enough about CVID to properly diagnose it. […] CVID mimics other conditions and, as a diagnosis of exclusion, can only be diagnosed once these conditions are ruled out, which can complicate diagnosis.

• #57 Common Variable Immunodeficiency (CVID): Diagnosis and More

  https://www.verywellhealth.com/common-variable-immunodeficiency-overview-and-more-5202552

  After gathering a health history of recurrent infections, CVID can be diagnosed through a series of blood tests. […] To be diagnosed with CVID, a person must have low immunoglobulins (antibodies). This includes low IgG and either IgM or IgA. It also requires a poor response to vaccines and the absence of any other disorder that causes an immunodeficiency. […] Getting diagnosed with CVID can be challenging in multiple ways: A person may become accustomed to their frequent infections and think of them as a fact of life, and subsequently delay seeking medical care. […] As a relatively rare disorder, many health providers do not know enough about CVID to properly diagnose it. […] CVID mimics other conditions and, as a diagnosis of exclusion, can only be diagnosed once these conditions are ruled out, which can complicate diagnosis.

• #58 Common Variable Immunodeficiency (CVID): Diagnosis and More

  https://www.verywellhealth.com/common-variable-immunodeficiency-overview-and-more-5202552

  After gathering a health history of recurrent infections, CVID can be diagnosed through a series of blood tests. […] To be diagnosed with CVID, a person must have low immunoglobulins (antibodies). This includes low IgG and either IgM or IgA. It also requires a poor response to vaccines and the absence of any other disorder that causes an immunodeficiency. […] Getting diagnosed with CVID can be challenging in multiple ways: A person may become accustomed to their frequent infections and think of them as a fact of life, and subsequently delay seeking medical care. […] As a relatively rare disorder, many health providers do not know enough about CVID to properly diagnose it. […] CVID mimics other conditions and, as a diagnosis of exclusion, can only be diagnosed once these conditions are ruled out, which can complicate diagnosis.

• #59 What Is Common Variable Immunodeficiency (CVID)? | SELF

  https://www.self.com/story/what-is-common-variable-immunodeficiency-cvid

  CVID is one of the most common primary immunodeficiency diseases (PIDD). […] This is particularly true of CVID, which is underrecognized, Dr. Hartog says. Doctors may generally assume that an underlying health concern, or the symptoms themselves, stem from a more common issue, Dr. Wada says. […] If your doctor does suspect you have CVID, theyll likely order a blood test or refer you to an immunologist. A low immunoglobulin level reading might signal the disease is present, but a specialist will usually also weigh other factorslike your history of infections and current symptomsto inform a diagnosis. […] It does take a bit of awareness and understanding to detect, Stanley A. Schwartz, MD, PhD, division chief of allergy, immunology, and rheumatology at the University at Buffalo, tells SELF. Digging into your health history is a great method of helping a clinician as they figure things out.

• #60 Common Variable Immunodeficiency (CVID): Diagnosis and More

  https://www.verywellhealth.com/common-variable-immunodeficiency-overview-and-more-5202552

  After gathering a health history of recurrent infections, CVID can be diagnosed through a series of blood tests. […] To be diagnosed with CVID, a person must have low immunoglobulins (antibodies). This includes low IgG and either IgM or IgA. It also requires a poor response to vaccines and the absence of any other disorder that causes an immunodeficiency. […] Getting diagnosed with CVID can be challenging in multiple ways: A person may become accustomed to their frequent infections and think of them as a fact of life, and subsequently delay seeking medical care. […] As a relatively rare disorder, many health providers do not know enough about CVID to properly diagnose it. […] CVID mimics other conditions and, as a diagnosis of exclusion, can only be diagnosed once these conditions are ruled out, which can complicate diagnosis.

• #61 Common Variable Immunodeficiency (CVID): Diagnosis and More

  https://www.verywellhealth.com/common-variable-immunodeficiency-overview-and-more-5202552

  Finally, in the past even experts had disagreed on the diagnostic criteria for CVID, such as whether a poor vaccine response is required to have CVID. […] As a result, diagnosis can be delayed from four to nine years after symptoms begin. […] Therefore, it’s essential to receive a timely, accurate diagnosis if you have symptoms of CVID.

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

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

  Approximately 25% of CVID patients develop autoimmune diseases, e.g., autoimmune thrombocytopenia, autoimmune hemolytic anemia, pernicious anemia, Addison disease, thyroiditis (Hashimoto/Graves), rheumatoid arthritis. […] 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 (7–19%). […] The leading autoimmune organ manifestations of CVID/SIgAD are cytopenia, followed by endocrinopathies, rheumatologic manifestations, and enteropathies (gastritis and hepatitis). […] The autoimmune diseases most often reported in CVID and in SigAD are the following: immune thrombocytopenia (ITP), found in around 14% of CVID patients; autoimmune hemolytic anemia (AIHA), found in up to 7%.

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

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

  Approximately 25% of CVID patients develop autoimmune diseases, e.g., autoimmune thrombocytopenia, autoimmune hemolytic anemia, pernicious anemia, Addison disease, thyroiditis (Hashimoto/Graves), rheumatoid arthritis. […] 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 (7–19%). […] The leading autoimmune organ manifestations of CVID/SIgAD are cytopenia, followed by endocrinopathies, rheumatologic manifestations, and enteropathies (gastritis and hepatitis). […] The autoimmune diseases most often reported in CVID and in SigAD are the following: immune thrombocytopenia (ITP), found in around 14% of CVID patients; autoimmune hemolytic anemia (AIHA), found in up to 7%.

• #64 The diagnosis of common variable immunodeficiency in adults should not be missed: A delayed diagnosis can be devastating | Allergologia et Immunopathologia

  https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-the-diagnosis-common-variable-immunodeficiency-S0301054613001985

  Early and accurate diagnosis of CVID can improve the quality of life, reduce morbidity and mortality of patients, and prevent economic losses due to wrong treatments or treatments of its complications. […] The patients with suspected CVID should be evaluated by the clinical immunologists as soon as possible.

• #65 The burden of common variable immunodeficiency disorders: a retrospective analysis of the European Society for Immunodeficiency (ESID) registry data | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0941-0

  Although a full unanimity regarding the definition of CVID does not exist at this point, a recent International Consensus on Common Variable Immunodeficiency Disorders (ICON) offers a good framework for the diagnosis of CVID. […] Diagnostic delay (median: 4 years) was associated with a higher risk of death: 1.04 (1.02; 1.06) p=0.0003, bronchiectasis: 1.03 (1.01; 1.04) p=0.0001, solid tumor: 1.08 (1.04; 1.11) p.0001 and enteropathy: 1.02 (1.00; 1.05) p=0.0447 and stayed unchanged over four decades (p=0.228). […] Diagnostic delay adjusted for the age at CVID symptoms onset was associated with the prevalence of bronchiectasis: HR (95% CI): 1.03 (1.01; 1.04) p=0.0001, solid tumor: 1.08 (1.04; 1.11) p.0001, and enteropathy: 1.02 (1.00; 1.05) p=0.0447. […] A comparison of three consecutive time periods of CVID diagnosis (1980; 1981-1999; and 2000) revealed no significant difference in diagnostic delay (independent sample Kruskal-Wallis test, p=0.228).

• #66 The diagnosis of common variable immunodeficiency in adults should not be missed: A delayed diagnosis can be devastating | Allergologia et Immunopathologia

  https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-the-diagnosis-common-variable-immunodeficiency-S0301054613001985

  Early and accurate diagnosis of CVID can improve the quality of life, reduce morbidity and mortality of patients, and prevent economic losses due to wrong treatments or treatments of its complications. […] The patients with suspected CVID should be evaluated by the clinical immunologists as soon as possible.

• #67 Common Variable Immunodeficiency (CVID) – Immune Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/immune-disorders/immunodeficiency-disorders/common-variable-immunodeficiency-cvid

  Common variable immunodeficiency is an immunodeficiency disorder characterized by very low antibody (immunoglobulin) levels despite a normal number of B cells (the type of white blood cell that makes antibodies). […] To diagnose the disorder, doctors measure immunoglobulin levels and determine how well the body produces immunoglobulins in response to vaccines. […] Doctors suspect common variable immunodeficiency when people have typical symptoms. […] Blood tests are done to measure immunoglobulin levels and to determine how well the body produces immunoglobulins in response to vaccines. […] If common variable immunodeficiency is diagnosed, doctors do tests yearly to check for disorders that commonly develop in people with this disorder, such as autoimmune disorders, cancers, and lung disorders.

• #68 Common Variable Immunodeficiency (CVID) – Immunology; Allergic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/immunology-allergic-disorders/immunodeficiency-disorders/common-variable-immunodeficiency-cvid

  Common variable immunodeficiency (CVID) is characterized by low immunoglobulin (Ig) levels with phenotypically normal B cells that can proliferate but do not develop into Ig-producing cells. Diagnosis is based mainly on serum Ig levels. […] Diagnosis of CVID is suggested by recurrent sinopulmonary infections and requires all of the following: Low (at least 2 standard deviations below the mean) levels of IgG, Low levels of IgA, IgM, or both, Impaired response to immunizations (usually both protein and polysaccharide vaccines), Exclusion of other immunodeficiency disorders. […] B-cell and T-cell quantification by flow cytometry is done to exclude other immunodeficiency disorders and to distinguish CVID from X-linked agammaglobulinemia, multiple myeloma, and chronic lymphocytic leukemia; findings may include low numbers of class-switched memory B cells or CD21+ cells.

• #69 Common Variable Immunodeficiency: Symptoms, Diagnosis & Treatment – The Kingsley Clinic

  https://thekingsleyclinic.com/resources/common-variable-immunodeficiency-symptoms-diagnosis-treatment/

  Mycophenolate mofetil is an immunosuppressive medication used to manage autoimmune complications in CVID patients. […] Azathioprine is another immunosuppressive medication used to treat autoimmune complications in CVID patients. […] Regular medical check-ups: Ongoing monitoring by a healthcare provider is essential for managing CVID effectively. […] Early diagnosis and treatment are crucial for managing the condition and preventing complications.

• #70 Common variable immune deficiency disorders – Immunodeficiency UKAccessibilityIncrease TextDecrease TextGrayscaleHigh ContrastNegative ContrastLight BackgroundLinks UnderlineReadable FontReset

  https://www.immunodeficiencyuk.org/common-variable-immune-deficiency-disorders/

  Common features leading to a diagnosis of CVID […] The diagnosis of a CVID is challenging because a doctor needs to exclude other reasons for the failure of antibody production. […] Diagnosis is confirmed by blood tests that check if there are low levels of serum IgG and IgA, and usually IgM. […] A clinical immunologist usually makes the diagnosis of a CVID. […] Lots of different genes may be altered in CVID, and sometimes genetic testing reveals that patients with more severe or unusual forms of a CVID have another related PID, often a combined immunodeficiency. […] The main treatment for a CVID is replacing the missing antibodies using immunoglobulin replacement therapy. […] Not all vaccines are safe to be administered to patients with a CVID and therefore you should discuss any recommended or required vaccinations with your clinical immunology team before receiving a vaccine.

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

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

  Histologic changes may be observed in the lymph nodes of patients with CVID. Findings may include the following: Reactive follicular hyperplasia. Atypical hyperplasia. Granulomatous inflammation. […] The mainstay of treatment for CVID is immunoglobulin replacement therapy, which reduces arthritic symptoms, infection recurrence, and the severity and/or incidence of the autoimmune disease. […] 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. […] In CVID, the T-cell compartment is strongly impacted, with premature arrest in thymic output, leading to T-cell exhaustion and immune dysregulation. […] 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.

Zobacz więcej