Materiały źródłowe

• #1 Primary immunodeficiency – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/primary-immunodeficiency/diagnosis-treatment/drc-20376910

  Treatments for primary immunodeficiency involve preventing and treating infections, boosting the immune system, and treating the underlying cause of the immune problem. In some cases, primary immune disorders are linked to a serious illness, such as an autoimmune disorder or cancer, which also needs to be treated. […] Infections require rapid and aggressive treatment with antibiotics. Treatment might require a longer course of antibiotics than is usually prescribed. Infections that don’t respond may require hospitalization and intravenous (IV) antibiotics. […] Some people need long-term antibiotics to prevent respiratory infections and permanent damage to the lungs and ears. […] Immunoglobulin consists of antibody proteins needed for the immune system to fight infections. It can either be injected into a vein through an intravenous (IV) line or inserted underneath the skin (subcutaneous infusion). treatment is needed every few weeks, and subcutaneous infusion is needed once or twice a week.

• #2 Treatment of patients with immunodeficiency: Medication, gene therapy, and transplantation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9432285/

  To provide an overview of drug treatment, transplantation, and gene therapy for patients with primary immunodeficiencies. […] The treatment of patients with primary immunodeficiencies aims to control their disease, especially the treatment and prevention of infections through antibiotic prophylaxis and/or immunoglobulin replacement therapy. In several diseases, it is possible to use specific medications for the affected pathway with control of the condition, especially in autoimmune or autoinflammatory processes associated with inborn immunity errors. In some diseases, treatment can be curative through hematopoietic stem cell transplantation (HSCT); more recently, gene therapy has opened new horizons through new technologies. […] Immunoglobulin replacement therapy remains the main therapeutic tool. Precision medicine with specific drugs for altered immune pathways is already a reality for several immune defects. Advances in the management of HSCT and gene therapy have expanded the capacity for curative treatments in patients with primary immunodeficiencies.

• #3 How can Primary Immunodeficiencies be treated? – ImmUnity Canada

  https://immunitycanada.org/info/treatments-primary-immunodeficiency/

  With proper treatment, many people with PI experience a dramatic improvement in their health, well-being and quality of life. […] The most common treatment option for PI patients is Immunoglobulin (Ig) replacement therapy. […] Ig replacement therapy can be administered in two ways: Intravenous (IVIg) through an IV needle and pump, usually given in a hospital or clinic setting once a month or; Subcutaneous (SCIg or SubQ ) through the fat tissues (stomach, thighs or upper arms), usually administered at home weekly. […] Hematopoietic Stem Cell Transplantation (HSCT) is typically used for patients with severe forms of primary immunodeficiency that are likely to cause significant harm or be fatal if not corrected. […] Newborn screening is critical for the early detection of severe primary immunodeficiency and successful treatment via stem cell transplantation.

• #4 Primary immunodeficiency – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/primary-immunodeficiency/symptoms-causes/syc-20376905

  Treatments can boost the immune system in many types of primary immunodeficiency disorders. […] Research is ongoing, leading to improved treatments and enhanced quality of life for people with the condition. […] Early diagnosis and treatment of primary immune deficiencies can prevent infections that can cause long-term problems.

• #5 The Treatment of Primary Immune Deficiencies: Lessons Learned and Future Opportunities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9247903/

  Primary immunodeficiency is a group of disorders associated with susceptibility to infectious agents and the development of various comorbidities. […] Major advances in the treatment of these disorders have occurred over the last half-century, and deeper molecular understanding of many disorders combined with clinically available genetic testing is allowing for use of precision therapy for several primary immunodeficiencies. […] Patients with antibody deficiencies who rely on immunoglobulin replacement therapy now have many treatment options with products that are much safer and better tolerated compared to the past. […] Early diagnosis of severe combined immunodeficiency allows infants to proceed to definitive therapy such as stem cell transplantation or gene therapy prior to facing potentially life-threatening infections.

• #6 Treatment of patients with immunodeficiency: Medication, gene therapy, and transplantation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9432285/

  The care and treatment of patients with IEI differ according to the result of the defect, the affected immune pathway, and the severity of each case. Therefore, an accurate diagnosis is crucial for adequate treatment, including general care, broad-spectrum or specific pharmacotherapies, such as the use of biological agents, and the use of curative therapies, such as bone marrow transplantation and gene therapy. […] Around 50%75% of IEI patients require immunoglobulin replacement, because antibody production is absent or inadequate. […] The main immunodeficiencies that require immunoglobulin replacement therapy are: Agammaglobulinemia, Hypogammaglobulinemia, Hyper-IgM syndrome, Antibody deficiency with normal levels of Immunoglobulins. […] The intravenous infusion of immunoglobulins is performed every three to four weeks, with an initial dose of 400600 mg/kg, so that the IgG level is 500 mg/dl in patients with agammaglobulinemia, with a consequent reduction in infections.

• #6 Treatment of patients with immunodeficiency: Medication, gene therapy, and transplantation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9432285/

  Most adverse effects associated with the intravenous infusion of immunoglobulins are related to the infusion rate. […] The expansion of knowledge on genetics and the pathophysiology of primary immunodeficiencies has increased the therapeutic arsenal for the treatment of these patients. Immunoglobulin replacement therapy remains the main therapeutic tool, as most patients with IEI have alterations in antibody quantity or quality. Precision medicine is already a reality for many patients with IEI in specific pathways, which can be treated with targeted medications for those pathways. Improvements in the management of HSCT in recent years have made it possible to transplant more and more patients with PID, offering curative therapy. In recent years, gene therapy has been successful and has become a hope for the future of patients with PIDs.

• #7 Primary Immunodeficiency: Types & Symptoms

  https://my.clevelandclinic.org/health/diseases/17964-primary-immunodeficiency

  Genetic mutations (changes) cause primary immunodeficiency. Theyre usually inherited, or passed down, within families, but can sometimes pop up sporadically. Providers treat primary immunodeficiency by preventing and managing infections and replacing missing or defective immune system components. […] If youve received a primary immunodeficiency diagnosis, your treatment goals will include managing current infections and preventing future infections. Your exact primary immunodeficiency treatment depends on the type of infection. […] Your healthcare provider may prescribe medications, including: Antibiotics to prevent or clear bacterial infections. Antivirals to help you recover from infections caused by viruses. Immune globulin, which you may receive in a vein (intravenously [IV]) or under your skin (subcutaneously), to replace some types of immune system components.

• #8 Primary Immunodeficiency Disease: Building a Treatment Plan – Allergy & Asthma Network

  https://allergyasthmanetwork.org/news/primary-immunodeficiency-disease-building-treatment-plan-with-therapy-options-and-community-support/

  Once diagnosed with PIDD, people can manage the disease by working with their doctor to develop a treatment plan that works for them. […] Recent treatment advances help prevent illnesses and infections in ways that meet the individual needs of patients. People with PIDD who have abnormally low or are unable to produce normal immune globulin (IG) levels, an antibody of human blood plasma, may benefit from IG replacement therapy to help the body ward off serious infections. […] PIDD patients will likely need treatment for the remainder of their life, so its important to customize IG replacement therapy to best fit the individuals routine and lifestyle. IG therapy is available in the form of an infusion, which can be administered intravenously (through a vein) or subcutaneously (under the skin).

• #8 Primary Immunodeficiency Disease: Building a Treatment Plan – Allergy & Asthma Network

  https://allergyasthmanetwork.org/news/primary-immunodeficiency-disease-building-treatment-plan-with-therapy-options-and-community-support/

  When developing a treatment plan for PIDD, patients should work with their healthcare providers to determine what treatment schedule and administration option will work best for their needs, taking into consideration the demands of their family and work life, their preferences for infusion frequency (from daily to monthly), and self-infusing at home or with the help of a healthcare professional. If lifestyle discussion is not part of the physician/patient relationship, patients should start the conversation.

• #9 IVIG for Primary Immunodeficiency: Mechanism, Benefits, and Cost – AmeriPharma® Specialty Care

  https://ameripharmaspecialty.com/ivig/ivig-for-primary-immunodeficiency-mechanism-benefits-and-cost/

  The starting IVIG dose for PI is 400 – 600 mg/kg every 3 to 4 weeks. Repeated doses at regular intervals are necessary because the body uses up externally administered antibodies for normal bodily processes. Since IVIG doesn’t stimulate the immune system, constant replenishment, usually for a lifetime, is essential. […] IVIG products have no absolute contraindications. Yet, they must be avoided or used with caution in certain situations. […] The amount you pay for IVIG treatment can vary, depending on your insurance plan, geographical location, and pharmacy.

• #10 Update on the treatment of primary immunodeficiencies | Allergologia et Immunopathologia

  https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-update-on-treatment-primary-immunodeficiencies-13110313

  Update on the treatment of primary immunodeficiencies […] A general review of advances in the treatment of Primary Immunodeficiencies (PID) has been performed. Treatment with immunoglobulins is indicated in cases of humoral immunodeficiencies and in selected cases of combined immunodeficiencies. The use of intramuscular immunoglobulins in the treatment of PID was abandoned after obtaining the intravenous immunoglobulins, since these are much more effective and have fewer adverse effects. Now subcutaneous immunoglobulins are also available. Immunoglobulins help to keep the patients free of symptoms and infections as these substances are able to neutralise infectious agents, modulate and promote the immune response and favour phagocytosis. Adverse effects have been reported in 5-15 % of patients receiving IVIg, and patients with deficiencies of subclasses of IgG with IgA deficiency and/or anti-IgA antibodies are at risk of severe reactions. No severe adverse effects of subcutaneous immunoglobulins have been reported and the medication can be self-administered. The efficacy and safety of IVIg and SCIg are similar and SCIg administered at home is associated with better quality of life. Stem Cell Transplantation (SCT) in Primary Immunodeficiencies is aimed at restoring the number and/or function of lymphocytes or phagocytes.

• #11 The Treatment of Primary Immune Deficiencies: Lessons Learned and Future Opportunities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9247903/

  More recently, recombinant human hyaluronidase has been used to facilitate infusions of 10% immunoglobulin. […] Currently, there are multiple products available for use in the USA and worldwide, some being specific to one of the three modes of administration routinely used. […] Various dosing regimens have been suggested over the years with the intention of preventing infection. […] When a fully HLA-matched sibling donor is used for SCT, no conditioning with chemotherapy is required for most forms of SCID. […] Hematopoietic stem cell transplant (HSCT or SCT) was first used as a curative therapy for a patient with SCID in 1968 by Dr. Robert A. Good. […] Gene therapy has been used to treat patients with T cell deficiencies such as IL2RG deficiency and ADA-SCID and can correct the immunologic defect.

• #12 FDA approves expansion of primary immunodeficiency medicine for treatment in children

  https://www.contemporarypediatrics.com/view/fda-approves-expansion-of-primary-immunodeficiency-medicine-for-treatment-in-children

  The FDA recently approved Hyqvia, expanding its use to treat pediatric patients with primary immunodeficiency (PI) aged 2 to 16 years. […] According to a recent FDA approval, immune globulin infusion 10% (Human) with recombinant human hyaluronidase (Hyqvia; Takeda) can now be used to treat children aged 2 to 16 years with primary immunodeficiency (PI). […] The approval of this new PI treatment for children 2 to 16 years old offers an alternative for health care providers and families who might prefer a less frequent treatment option that can be administered subcutaneously at home, after appropriate training, or in an infusion center. […] The FDA-approved expanded use of Hyqvia for pediatric patients comes after positive results were demonstrated in a prospective, non-controlled, open-label phase 3 clinical trial (NCT03277313).

• #13 Immune Deficiency Treatment Center | Immune Deficiency Doctors

  https://www.jaxallergy.com/allergy-treatments/immune-deficiency/

  Those with immune deficiency problems typically require much longer courses of antibiotics to successfully treat a particular infection than is required by patients with normally functioning immune systems. […] Immune deficiency treatment options may include antibody replacement therapy, often called IVIG therapy. This involves an infusion of antibodies to essentially replace the antibodies that your body fails to produce. Bone marrow transplantation, stem cell transplantation and gene therapy also are options for serious immune deficiency conditions.

• #14 Immunodeficiency Disorders Program | Rochester Regional Health

  https://www.rochesterregional.org/services/allergy-immunology-rheumatology/immunodeficiency-disorders-program

  Treatments for primary immunodeficiency typically involve preventing and treating infections, boosting your immune system, and treating the underlying causes of your immune disorder. Sometimes, primary immune disorders are also linked to a serious illnesslike cancer or an autoimmune disorderwhich also needs to be treated. […] Infections require quick and aggressive treatment with antibiotics. People suffering from immunodeficiencies may require a longer course of antibiotics than typically prescribed, and infections that do not respond may require hospitalizations and IV antibiotics. […] To prevent respiratory infections and permanent damage to the lungs and ears, some people need long-term antibiotics. In some cases, children with primary immunodeficiencies may be unable to have vaccines containing live viruses, like the MMR vaccine. Your provider will help you with prevention techniques and will answer any questions you may have.

• #15 The Treatment of Primary Immune Deficiencies: Lessons Learned and Future Opportunities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9247903/

  The lymphoproliferation associated with the combined immunodeficiency activated PI3K delta syndrome (APDS) has been successfully treated with PI3K inhibitors. […] Antimicrobial therapy is important for the treatment of all forms of immunodeficiency. […] Severe forms of immunodeficiency usually require antimicrobial prophylaxis regimens based on the known risk for infection, and a detailed description of these regimens is beyond the scope of this brief review. […] Infants with severe combined immunodeficiency (SCID) are typically managed with multiple forms of antimicrobial prophylaxis while moving toward definitive treatment such as stem cell transplant or gene therapy. […] More commonly, the treatment of primary immunodeficiencies that cause various levels of hypogammaglobulinemia also consists of the provision of antimicrobials to clear intercurrent infections.

• #16 Primary Immunodeficiencies | AAFP

  https://www.aafp.org/pubs/afp/issues/2003/1115/p2001.html

  Bone marrow transplants from HLA-identical donors can be curative in patients with cellular immune deficiencies such as severe combined immunodeficiency, Wiskott-Aldrich syndrome, and DiGeorge syndrome, and may be beneficial in patients with chronic granulomatous disease.4,14 Bone marrow transplantation currently has no role in the treatment of antibody deficiencies.9 […] When recurrent infections are a problem, many patients with primary immunodeficiencies are managed with antibiotics alone or in combination with IVIG. For example, in patients with chronic granulomatous disease, prophylactic therapy with trimethoprim-sulfamethoxazole (Bactrim, Septra) reduces the incidence of severe infections by 50 percent.4 Similarly, treatment for complement deficiencies is directed at preventing infection, and consists of antibiotic prophylaxis and immunizations for encapsulated bacteria (e.g., heptovalent pneumococcal vaccine, Haemophilus b conjugate vaccine, meningococcal polysaccharide vaccine).14 […] Other treatments for primary immunodeficiencies include enzyme replacement in patients with adenosine deaminase deficiency (a subtype of severe combined immunodeficiency) and cytokine therapy in patients with chronic granulomatous disease.8

• #17 Approach to the Patient With Suspected Immunodeficiency – Immunology; Allergic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/immunology-allergic-disorders/immunodeficiency-disorders/approach-to-the-patient-with-suspected-immunodeficiency

  Treatment of immunodeficiency disorders generally involves preventing infection, managing acute infection, and replacing missing immune components when possible. […] Infection can be prevented by advising patients to avoid environmental exposures and not giving them live-virus vaccines (eg, varicella, rotavirus, measles, mumps, rubella, herpes zoster, yellow fever, oral polio, intranasal influenza vaccines) or BCG (bacille Calmette-Gurin). […] Patients at risk of serious infections (eg, those with SCID, chronic granulomatous disease, Wiskott-Aldrich syndrome, or asplenia) or of specific infections (eg, with Pneumocystis jirovecii in patients with T-cell disorders) can be given prophylactic antibiotics (eg, trimethoprim/sulfamethoxazole 5 mg/kg orally twice a day). […] After appropriate cultures are obtained, antibiotics that target likely causes should be given promptly.

• #18 The Treatment of Primary Immune Deficiencies: Lessons Learned and Future Opportunities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9247903/

  For antibody deficiencies, these infections are typically caused by encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae, or other typical bacteria; therefore, it is important to select an antibiotic that will overcome known mechanisms of resistance to these drugs. […] The first use of immunoglobulin to treat a patient with antibody deficiency occurred in 1952 by Col Ogden Bruton, when he used subcutaneous immunoglobulin to successfully treat a boy with X-linked agammaglobulinemia. […] As the manufacturing processes and distribution of these lifesaving products improved over the next 25-50 years, the methods for infusion of IgG changed. […] Subcutaneous immunoglobulin (SCIG) has advantages over IVIG in regard to systemic tolerability although clinical efficacy is similar.

• #19 Primary immunodeficiency – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/primary-immunodeficiency/diagnosis-treatment/drc-20376910

  Stem cell transplantation offers a permanent cure for several forms of life-threatening immunodeficiency. Normal stem cells are transferred to the person with immunodeficiency, which results in a typically functioning immune system. […] Gene therapy involves taking stem cells from the person with primary immunodeficiency, correcting the gene in the cells and then returning the corrected stem cells back to the person via an intravenous infusion. With gene therapy, there is no need to find a suitable donor, as the person’s own cells are used. […] Depending on the type of disorder, treatment may involve other therapies, including enzyme replacement therapy or transplantation of the thymus, an organ located behind the breastbone (sternum) that produces T cells.

• #20 Primary Immunodeficiency | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/primary-immunodeficiency

  For some primary immunodeficiency disorders (PIDDs), these therapies can keep children healthy and active for many years. However, none of these therapies can cure the PIDD. The only known cure is hematopoietic stem cell transplantation or gene therapy. […] Currently, HSCT is the only non-experimental cure available. […] The only known cure is hematopoietic stem cell transplantation or gene therapy.

• #20 Primary Immunodeficiency | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/primary-immunodeficiency

  Primary immunodeficiency disorders (PIDDs) are a group of inherited conditions affecting the immune system, due to a lack of, or dysfunction of white blood cells, which have important roles in fighting infections. […] Thus, it’s critical to detect, diagnose and then treat the PID before it becomes a serious problem. […] More importantly, with early diagnosis and aggressive treatment, your child has an excellent chance to continue to live an active, productive life. Some of the most serious PIDDs can be completely cured with stem cell transplantation. This treatment replaces the defective white blood cells and reconstitutes the immune system. […] The most severe forms of PIDD may be cured by hematopoietic stem cell transplantation. However, most children with PIDD do not need this. […] There are several treatments we may recommend to support and improve the function of your child’s immune system, such as: gamma globulin (IgG) infusions – a procedure that supplements your child’s immune system with additional antibodies.

• #21

  https://link.springer.com/article/10.1007/s12016-022-08950-0

  Primary immunodeficiency is a group of disorders associated with susceptibility to infectious agents and the development of various comorbidities. […] Major advances in the treatment of these disorders have occurred over the last half-century, and deeper molecular understanding of many disorders combined with clinically available genetic testing is allowing for use of precision therapy for several primary immunodeficiencies. […] Patients with antibody deficiencies who rely on immunoglobulin replacement therapy now have many treatment options with products that are much safer and better tolerated compared to the past. […] Early diagnosis of severe combined immunodeficiency allows infants to proceed to definitive therapy such as stem cell transplantation or gene therapy prior to facing potentially life-threatening infections. […] While stem cell transplantation continues to carry significant risks, knowledge gained over recent decades is allowing for improved survival with less toxicity and less graft versus host disease. […] Treatment of primary immunodeficiency with allogeneic transplant and gene therapy.

• #22 Growth in diagnosis and treatment of primary immunodeficiency within the global Jeffrey Modell Centers Network | Allergy, Asthma & Clinical Immunology | Full Text

  https://aacijournal.biomedcentral.com/articles/10.1186/s13223-022-00662-6

  For patients reported to receive HSCT, stem cell donor type was assessed from 2013 to 2021. The number of patients treated by HSCT increased by 201%. Further, there was a 249% increase in matched donor transplants, a 190% increase in matched unrelated donor transplants, a 183% increase in mismatched unrelated donor transplants, and a 162% increase in parental haplo transplants. […] The substantial growth described above is partially due to newborn screening, molecular diagnosis, and NGS, and may need additional evaluation in the future. Notably, some Centers did not report treatment data, potentially due to access issues, data availability, or specific hospital guidelines.

• #23

  https://journals.lww.com/md-journal/fulltext/2023/03310/the_research_on_the_treatment_of_primary.59.aspx

  Hematopoietic stem cell transplantation (HSCT) is curative in patients with primary immunodeficiency syndrome. The safety and efficacy of HSCT as a therapeutic option for primary immunodeficiency diseases (PID) have been studied by many research groups. […] Numerous studies have shown that HSCT is the definitive treatment for children with rare primary immunodeficiency disorders. […] HSCT is an established curative treatment for many patients with PIDs. Donor selection, graft manipulation, conditioning and treatment of complications have improved incrementally, with survival and cure rates reaching 90% for some specific diseases. […] Therefore, the number of published scientific research on the treatment of PID by HSCT increased significantly since 2016. […] The use of allogeneic hematopoietic stem cells for the treatment of genetic blood cell disorders has become a clinical standard but is limited by the potential immunologic complications and availability of suitably matched donors. Gene therapy using autologous HSCs can avoid these limitations and thus may be safer.

• #23

  https://journals.lww.com/md-journal/fulltext/2023/03310/the_research_on_the_treatment_of_primary.59.aspx

  Advances in gene editing can now offer potentially effective options for treating PIDs, which are mostly monogenic diseases. […] CRISPR/Cas-mediated autologous HSCT is a prospective therapeutic option for different types of PIDs supported by preclinical gene-editing researches. […] Our study provided links among the top productive authors, group authors and keywords.

• #24 Gene therapy | Immune Deficiency Foundation

  https://primaryimmune.org/understanding-primary-immunodeficiency/treatment/gene-therapy

  Gene therapy is in clinical trials for several types of primary immunodeficiency (PI) and offers an alternative to hematopoietic stem cell transplantation when a suitable donor is not available. […] Gene therapy is not yet a Food and Drug Administration (FDA)-approved treatment for any PI and is only available through enrollment in a clinical trial in the U.S. […] If approved in the future, gene therapy will offer an important alternative to hematopoietic stem cell transplantation (HSCT) with a partial-match donor, such as a parent or unrelated donor. […] At this time, all FDA-approved gene therapies for non-PI conditions add a functional copy of a gene of interest to cells rather than directly editing gene variants. […] Overall, the growing experience with gene therapy has demonstrated that it is possible to successfully treat PI by inserting a functional copy of the gene into the individual’s stem cells. It is likely that many severe types of PI will be treated by gene therapy in the future.

• #25 Primary immunodeficiency – Wikipedia

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

  The treatment of primary immunodeficiencies depends foremost on the nature of the abnormality. Somatic treatment of primarily genetic defects is in its infancy. Most treatment is therefore passive and palliative, and falls into two modalities: managing infections and boosting the immune system. […] In the case of humoral immune deficiency, immunoglobulin replacement therapy in the form of intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) may be available. Antibiotic prophylaxis is also commonly used to prevent respiratory tract infections in these patients. […] For primary immunodeficiencies that are caused by genetic mutation does not exist a causal therapy that would „repair” the mutation. Although there is a therapeutic option, gene therapy which has been in a trial for few immune deficiencies affecting the hematopoietic system. Over the past two decades there were some successful treatments of patients with specific primary immunodeficiencies (PID), including X-linked severe combined immunodeficiency (SCID), WiskottAldrich syndrome and metabolic conditions such as leukodystrophy.

• #25 Primary immunodeficiency – Wikipedia

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

  Gene therapy evolved in the 90s from using of gammaretroviral vectors to more specific self-inactivating vector platforms around 2006. The viral vectors randomly insert their sequences into the genomes. However, it is rarely used because of a risk of developing post-treatment T-cell leukemia as a result of interfering tumor-suppressor genes and because of ethical issues. But the progress in gene therapy is promising for the future of treating primary immunodeficiencies.

• #26 Primary Immunodeficiency Diseases at CIIT – Seattle Children’s

  https://www.seattlechildrens.org/research/centers-programs/immunity-and-immunotherapies/translational-programs/primary-immunodeficiency-diseases/

  Our researchers are building a pipeline of gene therapies that could eventually be used to treat hundreds of genetic immune disorders. […] Our vision for the next generation of therapies for primary immunodeficiencies and other blood diseases is to insert corrective DNA directly into the mutant gene itself- a process called gene editing. […] Our scientists are rapidly advancing technologies that we will one day use to precisely edit defective genes in a patients own hematopoietic stem cells, in order to cure devastating immunodeficiency diseases such as immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX; FOXP3 gene mutation), X-linked hyper-IgM (X-HIGM; CD40L gene mutation), X-linked agammaglobulinemia (XLA; BTK gene mutation), Wiskott-Aldrich syndrome (WAS; WAS gene mutation).

• #27 The Treatment of Primary Immune Deficiencies: Lessons Learned and Future Opportunities

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9247903/

  While stem cell transplantation continues to carry significant risks, knowledge gained over recent decades is allowing for improved survival with less toxicity and less graft versus host disease. […] Identification of the molecular defect in such patients may allow for targeted treatments which are effective in controlling the dysregulated immune response without the wide-sweeping side effects which would otherwise occur with use of prolonged systemic steroids and other traditional antiinflammatory drugs. […] For example, patients with CTLA-4 deficiency may have a common variable immunodeficiency (CVID)like presentation along with severe symptoms of autoimmunity and immune dysregulation and may experience significant improvement when treated with CTLA-4 IgG fusion protein. […] Patients with STAT1-gain of function (GOF) or STAT3-GOF present with varying degrees of autoimmunity and may be treated with JAK inhibitors.

• #28 Primary Immunodeficiency (PID) – Australasian Society of Clinical Immunology and Allergy (ASCIA)

  https://www.allergy.org.au/patients/immunodeficiencies/primary-immunodeficiency

  Research and advances in therapies have resulted in improved health and a longer life for people with PID/IEI disorders. […] Infections should be treated early, and antibiotics are often required. Some people may be prescribed long term antibiotics (prophylaxis) to reduce infections. Medications against fungi, viruses and parasites may be needed to treat some conditions. […] Immunoglobulin replacement therapy (IRT) is one of the most effective and commonly used treatments for some PIDs. IRT can be given using intravenous immunoglobulin (IVIG), that is injected into the vein, or given at home using subcutaneous immunoglobulin (SCIG), that is injected under the skin. […] There is an increasing number of medications used to increase or decrease immune function. Medications may include corticosteroids, biologics such as monoclonal antibodies, and other immunosuppressive drugs.

• #29 Primary Immunodeficiency Disease (PIDD): List, Symptoms & Treatment

  https://www.medicinenet.com/primary_immunodeficiency_disease_pidd/article.htm

  Treatments for primary immunodeficiency disease include antibiotics to fight infection and depending upon the cause of the primary immunodeficiency disease, immune-boosting therapies. […] Stem cell transplantation may be an appropriate treatment for severe or life-threatening types of primary immunodeficiency disease. […] To treat recurrent infections antibiotics, antiviral medications, and antifungal drugs may be used. These medications may be stronger than those used to treat infections in people with a normally functioning immune system and may need to be administered intravenously (IV). Sometimes, long-term antibiotics are given to prevent the development of infections. […] To boost the immune system: The treatment for primary immunodeficiency disease depends upon the specific defect that is causing the immune system to malfunction. Examples of immune system treatments include: Intravenous or subcutaneous immunoglobulins provide antibodies to fight infection, Growth factor therapy if immune function deficiency is due to a lack of certain immune cells, Gamma interferon therapy involves administering a synthetic interferon (a substance that strengthens the immune system). This treatment is used for patients with chronic granulomatous disease.

• #30 New Primary Immunodeficiency treatments 2025 | Everyone.org

  https://everyone.org/explore/treatment/?id=87

  Prophylactic antibiotics are often used to prevent bacterial infections in patients with mild to moderate forms of immunodeficiency. […] Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment option for severe immunodeficiencies, such as severe combined immunodeficiency (SCID). […] Gene therapy is an emerging experimental treatment currently undergoing clinical trials. […] Thymus transplantation is an experimental therapy with limited FDA approval, primarily used to treat DiGeorge syndrome patients who lack thymic tissue. […] PEG-ADA enzyme replacement therapy is FDA-approved for ADA deficiency, providing enzyme replacement to reduce toxic metabolites and improve immune function. […] Interferon gamma therapy and immunomodulatory biologics are examples of off-label treatments used in specific circumstances.

• #31 Primary immunodeficiency | Allergy, Asthma & Clinical Immunology | Full Text

  https://aacijournal.biomedcentral.com/articles/10.1186/s13223-018-0290-5

  The treatment of PIDs is complex and generally requires both supportive and definitive strategies. […] Ig replacement therapy is the mainstay of therapy for B-cell disorders, and is also an important supportive treatment for many patients with combined immunodeficiency disorders. […] The treatment of innate immunodeficiency disorders varies depending on the type of defect, but may involve antifungal and antibiotic prophylaxis, cytokine replacement, vaccinations and bone marrow transplantation. […] Initial therapy for patients with SCID or other CIDs is supportive and involves aggressive management of the established infection, Ig replacement therapy, and antibiotic and antifungal prophylaxis to reduce the frequency and severity of infections. […] Since SCID is fatal unless the underlying defect is corrected, definitive therapy with bone marrow transplantation (BMT) or HSCT should be initiated as quickly as possible.

• #31 Primary immunodeficiency | Allergy, Asthma & Clinical Immunology | Full Text

  https://aacijournal.biomedcentral.com/articles/10.1186/s13223-018-0290-5

  The mainstay of therapy for most B-cell (antibody-deficiency) disorders is intravenous (IV) or subcutaneous Ig replacement therapy; in fact, many patients will require this treatment indefinitely. […] For patients with recurrent infections, prophylactic antibiotic therapy (particularly with agents that provide coverage of S. pneumoniae and H. influenzae) may also be needed in addition to Ig replacement therapy. […] The management of innate disorders depends on the type of defect. […] Gene therapy may also be a potential definitive treatment option in the future. […] There is no specific definitive therapy for complement deficiencies. Treatment of these disorders focuses on antibiotic prophylaxis for the prevention of recurrent infections.

• #32 Treatment and prognosis of common variable immunodeficiency – UpToDate

  https://www.uptodate.com/contents/treatment-and-prognosis-of-common-variable-immunodeficiency

  Treatment and prognosis of common variable immunodeficiency […] The cornerstone of therapy is immune globulin replacement, which has dramatically altered the clinical course of CVID by reducing the burden of recurrent infections and subsequent complications. […] Immune globulin replacement therapy may be administered either intravenously or subcutaneously. A typical approach is to begin therapy with intravenous immune globulin (IVIG), although one can also start with subcutaneous immune globulin (SCIG), with or without an initial loading regimen.

• #33 Overview of Immunodeficiency Disorders – Immune Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/immune-disorders/immunodeficiency-disorders/overview-of-immunodeficiency-disorders

  Treatment of immunodeficiency disorders usually involves preventing infections, treating infections when they occur, and replacing parts of the immune system that are missing when possible. […] With appropriate treatment, many people with an immunodeficiency disorder have a normal life span. However, some require intensive and frequent treatments throughout life. Others, such as those with severe combined immunodeficiency, die during infancy unless they are given a stem cell transplant. […] Strategies for preventing and treating infections depend on the type of immunodeficiency disorder. For example, people who have an immunodeficiency disorder due to a deficiency of antibodies are at risk of bacterial infections. The following can help reduce the risk: Practicing good personal hygiene (including conscientious dental care), Not eating undercooked food, Not drinking water that may be contaminated, Avoiding contact with people who have infections, Being treated periodically with immune globulin (antibodies obtained from the blood of people with a normal immune system) given intravenously or under the skin.

• #33 Overview of Immunodeficiency Disorders – Immune Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/immune-disorders/immunodeficiency-disorders/overview-of-immunodeficiency-disorders

  Vaccines are given if the specific immunodeficiency disorder does not affect antibody production. Vaccines are given to stimulate the body to produce antibodies that recognize and attack specific bacteria or viruses. […] Antibiotics are given as soon as a fever or another sign of an infection develops and often before surgical and dental procedures, which may introduce bacteria into the bloodstream. If a disorder (such as severe combined immunodeficiency) increases the risk of developing serious infections or particular infections, people may be given antibiotics long-term to prevent these infections. […] Immune globulin can effectively replace missing antibodies (immunoglobulins) in people with an immunodeficiency that affects antibody production by B cells. Immune globulin may be injected into a vein (intravenously) once a month or under the skin (subcutaneously) once a week or once a month. Subcutaneous immune globulin can be given at home, often by the person with the disorder.

• #34 Types of Treatment for Primary Immunodeficiency

  https://myigsource.com/primary-immunodeficiency-treatment-types

  There are many types of primary immunodeficiency (PI) diseases, and there are many approaches to treatment. What’s right for one type of PI may not be right for another. Sometimes, even people with the same type of PI may require different treatment plans to meet their specific needs. […] A PI treatment plan can and should be individualized per person, and may include: […] For people with PI involving a lack of antibodies (immunoglobulin, or Ig) that work the way they should, there are several types of therapies that can help provide protection from infection. These therapies are taken on a regular basis, and they often need to be taken throughout life. […] Ig treatment is used to temporarily replace some of the antibodies (immunoglobulins) that are missing or not working properly in people with PI.

• #35 Primary Immune Deficiency (PID) | CSL Behring Medical Affairs

  https://medicalaffairs.cslbehring.com/diseases-and-conditions/allergy-and-immunology/pid

  Primary Therapy – Immunoglobulin […] Ig therapy (IV or SC) is required for patients with PID characterized by impaired antibody production, usually accompanied by recurrent or unusually severe infection. […] Mandatory for patients with severe PIDs that directly impact B-cell function and antibody production. […] Increasingly seen as important in other PIDs in which antibody or B-cell dysfunction is implicated but may not be as apparent in conventional testing. […] Patients receiving Ig therapy should have regular monitoring of IgG trough levels, blood cell counts, and serum chemistry. […] IVIg therapy is indicated as replacement therapy for patients with PID characterized by absent or deficient antibody production. […] IVIg is indicated as continuous replacement therapy for primary immunodeficiency. Treatment should not be interrupted once a definitive diagnosis has been established.

• #36 Primary Immunodeficiency Disorders (PIDD) | UVA Health

  https://uvahealth.com/services/allergy/pidd

  As you go through this process, were with you at every step. Well thoroughly investigate your condition and plot a course of treatment unique to you. […] Treatment: Youll most likely need medication specific to your unique situation. Since the process to obtain these medications can be complex and difficult to manage, we have a dedicated team to help you get what you need. […] Regular follow-up visits: Well need to see you regularly to monitor your health and evaluate the success of the medication. Well make treatment adjustments as needed and watch for any changes or complications of your disease. […] An established network of specialists with expertise in specific PIDD complications help us develop the best strategies for treatment.

• #37 Primary Immunodeficiency Treatment | Soleo Health

  https://www.soleohealth.com/primary-immunodeficiency-treatment/

  The treatment can be given in two ways: Intravenously (IVIG) directly into a vein at an infusion center or at home. […] Subcutaneously (SCIG) under the skin, typically self-administered at home. […] Most patients notice improvements within 3-6 months after starting immunoglobulin replacement therapy. […] Most insurance plans, including Medicare and Medicaid, cover immunoglobulin therapy and other primary immunodeficiency treatments. […] Our Therapy care management teams, including specially trained pharmacists and registered nurses, focus on providing personalized specialty care.

• #38 Overview of gene therapy for inborn errors of immunity – UpToDate

  https://www.uptodate.com/contents/overview-of-gene-therapy-for-inborn-errors-of-immunity

  Gene therapy (GT) for inborn errors of immunity (IEI; previously called primary immunodeficiency disorders [PIDs]) involves restoring a functional copy of the defective gene into the affected patient’s own hematopoietic stem cells (HSCs) by gene addition or gene editing. […] It is one of the two modalities with the potential to cure patients with IEI, the other being hematopoietic cell transplantation (HCT), which provides healthy donor HSCs that will differentiate into mature functional immune cells in an affected patient. […] Traditionally, GT is accomplished by removing HSCs from an affected patient, adding ex vivo a corrected gene copy that integrates into chromosomal deoxyribonucleic acid (DNA; gene addition), and then returning the cells to the patient. […] Potential alternatives or adjunctive approaches to gene addition therapy or HCT are under development, including gene editing approaches.

• #39 Overview of gene therapy for inborn errors of immunity – UpToDate

  https://www.uptodate.com/contents/overview-of-gene-therapy-for-inborn-errors-of-immunity

  The use of standard and alternative approaches to GT for IEI are reviewed in this topic and are discussed in general separately. […] An alternative, potentially safer approach is using the patient’s own (autologous) hematopoietic stem cells (HSCs) with the disease-related gene corrected to eliminate the risks of graft rejection or graft-versus-host disease. […] Traditional GT (gene addition) uses the unique ability of certain viruses to integrate into the host genome. […] Modified viruses into which IEI genes have been introduced while removing the ability to self-replicate have made possible ex vivo correction of certain IEI genotypes. […] Retroviruses including gamma retroviruses (eg, Moloney murine leukemia virus [MMLV]) and lentiviruses (eg, human immunodeficiency virus [HIV]), have been exploited for therapeutic applications where stable, long-term integration of a correct complementary DNA (cDNA) into host hematopoietic stem cells (HSCs) is required. […] Lentiviral vectors have an advantage over first-generation retroviruses in that they are able to infect both nondividing and dividing cells, leading to increased transduction efficiency compared with gamma-retroviral vectors, which can only infect dividing cells.

• #40

  https://www.mattioli1885journals.com/index.php/actabiomedica/article/view/12406

  Primary immunodeficiency disorders (PIDs) are rare inherited monogenic disorders of the immune system, characterized by an increased risk of infection, immune dysregulation and malignancies. […] In PID, targeted therapies are especially effective to manage immune dysregulation and autoimmunity, also reducing the incidence of side effects compared to conventional treatments, sparing the use of steroids and immunosuppressive drugs. […] Moreover, in the last years, the approach of conventional treatments such as immunoglobulin replacement therapies has evolved and the indication has expanded to new diseases, leading to individualized strategies to both improve infection control and quality of life. […] Similarly, the new advent of gene therapy in selected PIDs has introduced the benefit to correct the immunological defect, reducing at the same time the complications related to the hematopoietic stem cell transplantation. […] Here, we illustrate the most recent findings on tailored treatments for PIDs.

• #41 Clinical Sites | Primary Immune Deficiency Treatment Consortium

  https://pidtc.rarediseasesnetwork.org/clinical-sites

  This study focuses on the natural history of patients with PIRD to help collect data on ideal therapies for these patients. […] This study will help characterize the clinical symptoms and responses to treatments both medications and bone marrow transplant. […] Individuals with a possible diagnosis of severe combined immune deficiency (including infants who were identified by newborn screening) may be eligible to be enrolled on the PIDTC research study 6907. […] The 6907 research study does NOT dictate how your / your childs doctors should treat you / your child, as the PIDTC recognizes that there are many complex factors that go into this decision. […] The decision about how you / your child with SCID will be treated is made by your doctor. […] This study aims to evaluate patients with SCID to understand the neurodevelopmental (ND) problems following either bone marrow transplantation (BMT) also called hematopoietic cell transplantation (HCT) or gene therapy to determine if ND will be reduced in patients who are diagnosed via newborn screening compared to those diagnosed following an infection.

• #42 Clinical Sites | Primary Immune Deficiency Treatment Consortium

  https://pidtc.rarediseasesnetwork.org/clinical-sites

  The 6907 study simply follows how you / your child do over time. There are no experimental therapies on this study. […] The study will collect data yearly from the clinical record. […] If the patient receives a bone marrow transplant, research samples will be collected one month prior to transplant and a year later. […] The 6907 research study does NOT dictate how your / your childs doctors should treat you / your child, as the PIDTC recognizes that there are many complex factors that go into this decision. […] The decision about how you / your child with SCID will be treated is made by your doctor. […] Understanding ND problems in this population of patients is critical for guiding clinicians to determine the best treatment strategy for treating patients with SCID.

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