Materiały źródłowe

• #1 X-Linked Agammaglobulinemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549865/

  X-linked agammaglobulinemia or XLA is a primary immunodeficiency disorder that prevents affected individuals from making antibodies and requires them to rely on lifelong immunoglobulin replacement therapy for survival. […] There is currently no cure for XLA; however, early management with immunoglobulin replacement therapy and antibiotics to prevent and treat infections. […] The optimal management of patients with XLA includes: Regular immunoglobulin replacement therapy, using intravenous or subcutaneous infusions; Therapeutic and prophylactic use of antibiotics to treat and prevent bacterial infections; Careful monitoring to manage reactions arising from immunoglobulin infusions, complications of infections, or the emergence of clinical disease (e.g., autoimmune, inflammatory, malignant); Support (nutritional, social, psychological, and educational); Counseling about the importance of receiving all available immunizations except for those containing live bacteria or viruses. […] Immunoglobulin replacement therapy has been used for decades and continues to be the core treatment modality for patients with XLA. […] Overall, an interprofessional team approach to the treatment of patients with XLA is the proper management methodology.

• #2 X-Linked (Bruton) Agammaglobulinemia Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1050956-treatment

  No curative therapy exists for X-linked agammaglobulinemia (XLA), or Bruton agammaglobulinemia. Treatment for XLA is IVIG. Typical doses are 400-600 mg/kg/mo given every 3-4 weeks. Doses and intervals can be adjusted based on individual clinical responses. Therapy should begin at age 10-12 weeks. Maintenance of an IgG trough level of 500-800 mg/dL is recommended. Therapy should be started at age 10-12 weeks. Currently, no evidence supports that one particular brand or route of administration (IV vs SC) is better than the other. […] Antibiotics, such as amoxicillin and amoxicillin/clavulanate, are administered for common sinopulmonary infections. Pending culture sensitivities, intravenous ceftriaxone may be used for chronic infections, pneumonia, or sepsis. […] Bronchodilators, steroid inhalers, and regular pulmonary function tests (at least 3-4 times a year) may be a required part of therapy in addition to antibiotics.

• #3 X-linked agammaglobulinemia // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/x-linked-agammaglobulinemia

  There’s no cure for XLA. Treatment aims at boosting the immune system to prevent infections. There also is quick treatment for infections as they happen. […] Medicines to treat XLA include: […] Gammaglobulin. This is a type of protein found in blood that contains antibodies against infections. It’s put into a vein, called infusion, every 2 to 4 weeks or given with weekly shots. […] Antibiotics. Some people with XLA take antibiotics all the time to prevent infections. Others take antibiotics for bacterial infections longer than do people without XLA. […] Your healthcare professional likely will suggest that you have follow-up visits every 6 to 12 months to screen for complications of XLA. You’ll also likely be told to not get live vaccines, such as live polio, measles-mumps-rubella or chickenpox vaccines.

• #4 X-Linked Agammaglobulinemia (XLA) – AmeriPharma® Specialty Care

  https://ameripharmaspecialty.com/other-health-conditions/x-linked-agammaglobulinemia/

  Early diagnosis of agammaglobulinemia and several treatment therapies (antibiotics and immunoglobulin replacement therapy) may help to enhance life expectancy and allow agammaglobulinemia patients to live a relatively normal and active life. There is no curative therapy for agammaglobulinemia genetic disorder. The goal of currently available treatment therapy is to boost the immune system of an individual with XLA and prevent recurrent infections. […] The main goals for treatment are to prevent organ damage, decrease disease severity, reduce morbidity, treat any infections, and improve health-related quality of life. […] Bacterial infections are treated with antibiotics. Those who get severe or frequent bacterial infections may need to take antibiotics for several months at a time to prevent them from recurring.

• #5 X-linked agammaglobulinemia | Children’s Wisconsin

  https://childrenswi.org/medical-care/immune-deficiency/immune-disorders/x-linked-agammaglobulinemia

  Specific treatment for X-linked agammaglobulinemia will be determined by your child’s physician based on: […] Treatment for X-linked agammaglobulinemia may include […] antibody replacement – through gamma globulin therapy, IVIG (given intravenously into the bloodstream). This treatment gives patients the antibodies that they cannot make themselves, in order to protect against infections and reduce the spread of infections. […] prompt treatment of infections (or giving antibiotics prophylactically before an infection has occurred). […] avoidance of live viral vaccinations (such as the one given for measles, mumps, rubella (MMR) and chickenpox (varicella), because your child could develop the disease for which the vaccine was given.) […] Without antibody replacement, these children could die at an early age from severe infections. Children who develop chronic lung disease with bronchiectasis (widening and scarring of the airways) may have a shortened lifespan, in some cases. However, those children with X-linked agammaglobulinemia who are diagnosed and treated early should be able to lead normal, active lives.

• #6 X-Linked Agammaglobulinemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549865/

  X-linked agammaglobulinemia or XLA is a primary immunodeficiency disorder that prevents affected individuals from making antibodies and requires them to rely on lifelong immunoglobulin replacement therapy for survival. […] There is currently no cure for XLA; however, early management with immunoglobulin replacement therapy and antibiotics to prevent and treat infections. […] The optimal management of patients with XLA includes: Regular immunoglobulin replacement therapy, using intravenous or subcutaneous infusions; Therapeutic and prophylactic use of antibiotics to treat and prevent bacterial infections; Careful monitoring to manage reactions arising from immunoglobulin infusions, complications of infections, or the emergence of clinical disease (e.g., autoimmune, inflammatory, malignant); Support (nutritional, social, psychological, and educational); Counseling about the importance of receiving all available immunizations except for those containing live bacteria or viruses. […] Immunoglobulin replacement therapy has been used for decades and continues to be the core treatment modality for patients with XLA. […] Overall, an interprofessional team approach to the treatment of patients with XLA is the proper management methodology.

• #7 X-Linked Agammaglobulinemia | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/31430

  X-linked agammaglobulinemia or XLA is one of the most common pediatric primary immunodeficiencies that prevent affected individuals from making antibodies and requires lifelong immunoglobulin replacement therapy for survival. […] There is currently no cure for XLA; however, early management with immunoglobulin replacement therapy and antibiotics to prevent and treat infections. Although this lifelong avenue is costly, it has been the mainstay of treatment for the past fifty years. […] The optimal management of patients with XLA includes regular immunoglobulin replacement therapy, using intravenous or subcutaneous infusions, therapeutic and prophylactic use of antibiotics to treat and prevent bacterial infections, careful monitoring to manage reactions arising from immunoglobulin infusions, complications of infections, or the emergence of clinical disease, support (nutritional, social, psychological, and educational), and counseling about the importance of receiving all available immunizations except for those containing live bacteria or viruses. […] Immunoglobulin replacement therapy has been used for decades and continues to be the core treatment modality for patients with XLA. […] The current mainstay of treatment is with intravenous immunoglobulin.

• #8 X-linked agammaglobulinemia – Wikipedia

  https://en.wikipedia.org/wiki/X-linked_agammaglobulinemia

  XLA is treated by infusion of human antibody. Treatment with pooled gamma globulin cannot restore a functional population of B cells, but it is sufficient to reduce the severity and number of infections due to the passive immunity granted by the exogenous antibodies. […] The most common treatment for XLA is an intravenous infusion of immunoglobulin (IVIg, human IgG antibodies) every week, for life. IVIg does not cure XLA but increases the patient’s lifespan and quality of life, by generating passive immunity, and boosting the immune system. […] With treatment, the number and severity of infections is reduced. With IVIg, XLA patients may live a relatively healthy life. […] Muscle injections of immunoglobulin (IMIg) were common before IVIg was prevalent, but are less effective and much more painful; hence, IMIg is now uncommon. Subcutaneous treatment (SCIg) was recently approved by the U.S. Food and Drug Administration (FDA), which is recommended in cases of severe adverse reactions to the IVIg treatment.

• #9 X-linked agammaglobulinemia medical therapy – wikidoc

  https://wikidoc.org/index.php/X-linked_agammaglobulinemia_medical_therapy

  The most common treatment for XLA is an intravenous infusion of immunoglobulin (IVIg, human IgG antibodies) every 3-4 weeks, for life. IVIg is a human product extracted and pooled from thousands of blood donations. IVIg does not cure XLA but increases the patient’s lifespan and quality of life, by generating passive immunity, and boosting the immune system. With treatment, the number and severity of infections is reduced. With IVIg, XLA patients may a live relatively healthy life. A patient should attempt reaching a state where his IgG blood count exceeds 800 mg/Kg. The dose is based on the patient’s weight and IgG blood-count. The dosing rule of thumb is 1g of IVIg for every 2kg of patient’s weight. […] Muscle injections of immunoglobulin (IMIg) were common before IVIg was prevalent, but are less effective and much more painful, hence, IMIg is now uncommon.

• #10 X-Linked Agammaglobulinemia (XLA) – AmeriPharma® Specialty Care

  https://ameripharmaspecialty.com/other-health-conditions/x-linked-agammaglobulinemia/

  The first and foremost goal is to protect patients from getting bacterial infections by maintaining good hygiene (frequent hand washing) and drinking treated water. […] Immunoglobulin replacement therapy (IRT) is a standard, lifelong, and life-saving treatment for XLA. IRT not only boosts the patient’s immune system but also improves the patient’s survival rate and quality of life by providing the missing immunoglobulins in the body. […] Intravenous immunoglobulin (IVIG) therapy is administered in the veins every 3 to 4 weeks. […] An alternative to IVIG therapy, subcutaneous immunoglobulin therapy (SCIG), may be chosen as an option due to IVIG adverse reactions or difficulty with IV access. […] Another alternative to IVIG therapy is intramuscular immunoglobulin therapy. […] IRT therapy is prepared from a donor pool; it does not provide immunity to unexposed pathogens.

• #11 Clinical and immunological analysis of patients with X-linked agammaglobulinemia – single center experience

  https://www.termedia.pl/Clinical-and-immunological-analysis-of-patients-with-X-linked-agammaglobulinemia-single-center-experience,10,21451,1,1.html

  The first description of X-linked agammaglobulinemia (XLA) comes from 1952 when Dr O. Bruton described a boy with recurrent infection treated successfully with immunoglobulins. […] To prevent them, life-long immunoglobulin replacement therapy is indicated. […] The immunoglobulin infusions were administered sporadically in a few individuals with very serious infections as a supportive therapy prior to clinical diagnosis. Replacement immunoglobulin therapy was introduced at the mean age of 3 years and 5 months and was generally delayed in comparison to the disease onset. All discussed patients were treated with intravenous immunoglobulin (IVIG), with a mean dose of 0.4-0.6 g/kg, given every 3 or 4 weeks. […] In 2001, treatment with subcutaneous immunoglobulin (SCIG) was initiated in a group of 15 patients with PAD, among them in 9 with XLA. An equivalent monthly dose, divided into 4 weekly infusions, was given i.e. approximately 0.1-0.15 g/kg/week. Patients and their families generally preferred SCIG than IVIG due to the possibility of self-infusions at home, less frequent visits to the hospital, and a more comfortable lifestyle.

• #12 X-linked agammaglobulinemia medical therapy – wikidoc

  https://wikidoc.org/index.php/X-linked_agammaglobulinemia_medical_therapy

  The most common treatment for XLA is an intravenous infusion of immunoglobulin (IVIg, human IgG antibodies) every 3-4 weeks, for life. IVIg is a human product extracted and pooled from thousands of blood donations. IVIg does not cure XLA but increases the patient’s lifespan and quality of life, by generating passive immunity, and boosting the immune system. With treatment, the number and severity of infections is reduced. With IVIg, XLA patients may a live relatively healthy life. A patient should attempt reaching a state where his IgG blood count exceeds 800 mg/Kg. The dose is based on the patient’s weight and IgG blood-count. The dosing rule of thumb is 1g of IVIg for every 2kg of patient’s weight. […] Muscle injections of immunoglobulin (IMIg) were common before IVIg was prevalent, but are less effective and much more painful, hence, IMIg is now uncommon.

• #13 Immunodeficiency Search

  https://www.immunodeficiencysearch.com/x-linked-agammaglobulinemia

  Immunoglobulin replacement therapy is the cornerstone of therapy for XLA patients. […] Replacement of serum IgG with monthly IVIG or weekly subcutaneous (SC) Ig is the cornerstone of therapy. Typical replacement is started with 400-600mg/kg of IVIG every 4 weeks or 100-150mg/kg of SCIg every week. Trough IgG levels should be checked after 5 IVIG doses. It is clear that patients who maintain trough IgG levels above 700-900mg/dl have fewer infectious complications. SCIg is ideal for patients who benefit from maintaining steady serum levels of immunoglobulins or who are unable to tolerate IVIG due to adverse side effects (headache, chills, nausea, thrombotic events). […] The addition of prophylactic antibiotics can be considered in patients who continue to have infections despite appropriate immunoglobulin replacement. Two sample prophylaxis regimens are listed below: 1. Amoxicillin 20mg/kg divided twice daily. Maximum of 500mg twice daily. 2. Azithromycin 10mg/kg once weekly. Maximum of 1 gram once weekly.

• #14 X-Linked (Bruton) Agammaglobulinemia Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1050956-treatment

  No curative therapy exists for X-linked agammaglobulinemia (XLA), or Bruton agammaglobulinemia. Treatment for XLA is IVIG. Typical doses are 400-600 mg/kg/mo given every 3-4 weeks. Doses and intervals can be adjusted based on individual clinical responses. Therapy should begin at age 10-12 weeks. Maintenance of an IgG trough level of 500-800 mg/dL is recommended. Therapy should be started at age 10-12 weeks. Currently, no evidence supports that one particular brand or route of administration (IV vs SC) is better than the other. […] Antibiotics, such as amoxicillin and amoxicillin/clavulanate, are administered for common sinopulmonary infections. Pending culture sensitivities, intravenous ceftriaxone may be used for chronic infections, pneumonia, or sepsis. […] Bronchodilators, steroid inhalers, and regular pulmonary function tests (at least 3-4 times a year) may be a required part of therapy in addition to antibiotics.

• #15 Orphanet: X-linked agammaglobulinemia

  https://www.orpha.net/en/disease/detail/47

  There is no curative treatment for XLA but good disease control can be achieved through consistent gammaglobulin therapy. This can be given intravenously (400-600 mg/kg every 3 to 4 weeks) or subcutaneously (100 mg/kg every week). Therapy should be started as early as possible. Some immunologists advocate chronic prophylactic antibiotics and treatment of acute infections should be prolonged and at maximal doses of antibiotics.

• #16 X-Linked (Bruton) Agammaglobulinemia Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1050956-treatment

  No curative therapy exists for X-linked agammaglobulinemia (XLA), or Bruton agammaglobulinemia. Treatment for XLA is IVIG. Typical doses are 400-600 mg/kg/mo given every 3-4 weeks. Doses and intervals can be adjusted based on individual clinical responses. Therapy should begin at age 10-12 weeks. Maintenance of an IgG trough level of 500-800 mg/dL is recommended. Therapy should be started at age 10-12 weeks. Currently, no evidence supports that one particular brand or route of administration (IV vs SC) is better than the other. […] Antibiotics, such as amoxicillin and amoxicillin/clavulanate, are administered for common sinopulmonary infections. Pending culture sensitivities, intravenous ceftriaxone may be used for chronic infections, pneumonia, or sepsis. […] Bronchodilators, steroid inhalers, and regular pulmonary function tests (at least 3-4 times a year) may be a required part of therapy in addition to antibiotics.

• #17 X-linked Agammaglobulinemia (Congenital Agammaglobulinemia, Bruton’s Agammaglobulinemia – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/x-linked-agammaglobulinemia-congenital-agammaglobulinemia-brutons-agammaglobulinemia/

  Optimal patient management involves a number of strategies. […] First and foremost is replacement immunoglobulin therapy. Whether the patient is treated with intravenous or subcutaneous IgG, the aim is to maintain his trough level (the level immediately before his next treatment) of IgG above 500mg/dL and/or an increment of 400mg above his pretreatment level. Monitoring trough IgG levels monthly in the first few months after initiating IgG replacement therapy and semi-annually thereafter can be very helpful in deciding dose and frequency of replacement therapy. Importantly, if the clinical response in terms of infection is not satisfactory, then increasing the dose of IgG may be desirable. […] Antibiotics should be used early in the course of any possible bacterial infection. […] Finally, the patients family should be instructed in the way in which the disease is inherited (X-linked) and the implications of that form of inheritance on future pregnancies of his parents and on the carrier status of sisters, maternal aunts and maternal cousins. When patient reaches an appropriate age, he should be counseled as to the risk of his daughters being a carrier (100%) and his sons being affected (0%)

• #18 Immunodeficiency Search

  https://www.immunodeficiencysearch.com/x-linked-agammaglobulinemia

  Immunoglobulin replacement therapy is the cornerstone of therapy for XLA patients. […] Replacement of serum IgG with monthly IVIG or weekly subcutaneous (SC) Ig is the cornerstone of therapy. Typical replacement is started with 400-600mg/kg of IVIG every 4 weeks or 100-150mg/kg of SCIg every week. Trough IgG levels should be checked after 5 IVIG doses. It is clear that patients who maintain trough IgG levels above 700-900mg/dl have fewer infectious complications. SCIg is ideal for patients who benefit from maintaining steady serum levels of immunoglobulins or who are unable to tolerate IVIG due to adverse side effects (headache, chills, nausea, thrombotic events). […] The addition of prophylactic antibiotics can be considered in patients who continue to have infections despite appropriate immunoglobulin replacement. Two sample prophylaxis regimens are listed below: 1. Amoxicillin 20mg/kg divided twice daily. Maximum of 500mg twice daily. 2. Azithromycin 10mg/kg once weekly. Maximum of 1 gram once weekly.

• #19 X-linked Agammaglobulinemia (Congenital Agammaglobulinemia, Bruton’s Agammaglobulinemia – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/x-linked-agammaglobulinemia-congenital-agammaglobulinemia-brutons-agammaglobulinemia/

  Optimal patient management involves a number of strategies. […] First and foremost is replacement immunoglobulin therapy. Whether the patient is treated with intravenous or subcutaneous IgG, the aim is to maintain his trough level (the level immediately before his next treatment) of IgG above 500mg/dL and/or an increment of 400mg above his pretreatment level. Monitoring trough IgG levels monthly in the first few months after initiating IgG replacement therapy and semi-annually thereafter can be very helpful in deciding dose and frequency of replacement therapy. Importantly, if the clinical response in terms of infection is not satisfactory, then increasing the dose of IgG may be desirable. […] Antibiotics should be used early in the course of any possible bacterial infection. […] Finally, the patients family should be instructed in the way in which the disease is inherited (X-linked) and the implications of that form of inheritance on future pregnancies of his parents and on the carrier status of sisters, maternal aunts and maternal cousins. When patient reaches an appropriate age, he should be counseled as to the risk of his daughters being a carrier (100%) and his sons being affected (0%)

• #20 X-linked agammaglobulinemia – Wikipedia

  https://en.wikipedia.org/wiki/X-linked_agammaglobulinemia

  XLA is treated by infusion of human antibody. Treatment with pooled gamma globulin cannot restore a functional population of B cells, but it is sufficient to reduce the severity and number of infections due to the passive immunity granted by the exogenous antibodies. […] The most common treatment for XLA is an intravenous infusion of immunoglobulin (IVIg, human IgG antibodies) every week, for life. IVIg does not cure XLA but increases the patient’s lifespan and quality of life, by generating passive immunity, and boosting the immune system. […] With treatment, the number and severity of infections is reduced. With IVIg, XLA patients may live a relatively healthy life. […] Muscle injections of immunoglobulin (IMIg) were common before IVIg was prevalent, but are less effective and much more painful; hence, IMIg is now uncommon. Subcutaneous treatment (SCIg) was recently approved by the U.S. Food and Drug Administration (FDA), which is recommended in cases of severe adverse reactions to the IVIg treatment.

• #21

  https://link.springer.com/article/10.1007/s10875-024-01829-z

  X-linked agammaglobulinaemia (XLA), caused by mutations in BTK, is characterised by low or absent peripheral CD19+B lymphocytes and agammaglobulinaemia. The mainstay of treatment consists of immunoglobulin replacement therapy (IgRT). […] Despite modern therapy, most XLA patients continue to experience complications, most notably bronchiectasis, likely due to absence of IgA/M in current therapies, but lack of B lymphocytes may also lead to additional sequalae. These data strongly support the need for further research, particularly that of curative modalities including HSCT and gene therapy. […] Since the first case report, the foundation of treatment continues to be immunoglobulin replacement therapy (IgRT). […] However, there are concerns that despite modern IgRT, XLA patients continue to experience significant infectious and non-infectious complications.

• #22 Mortality and morbidity in patients with X-linked agammaglobulinaemia | Allergologia et Immunopathologia

  https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-mortality-morbidity-in-patients-with-S0301054613002863

  X-linked agammaglobulinaemia (XLA) is a genetic disorder characterised by a defect in the generation of mature B cells, lack of antibodies production, and susceptibility to recurrent bacterial infections. […] Over the past decades, the mortality and morbidity of XLA patients have been significantly reduced by the use of IVIG replacement therapy. […] However, its usage is only in the management of the disease instead of its cure, and is associated with several long-term complications and its beneficial effect has been more pronounced for the control of systemic rather than of mucosal infections. […] Despite recent advances in the treatment of XLA, these patients still suffer from severe complications. […] The main cause of mortality in our patients was respiratory failure due to the chronic respiratory infections which suggests that, despite appropriate serum IgG level of patients during follow-up period, chronic lung disease (CLD) remains the most dangerous complication in XLA patients.

• #23 X-Linked Agammaglobulinemia (XLA) – AmeriPharma® Specialty Care

  https://ameripharmaspecialty.com/other-health-conditions/x-linked-agammaglobulinemia/

  IVIG and SCIG therapies only replace IgG immunoglobulins, not other immunoglobulin isotypes such as IgA and IgM. […] IRT is usually very expensive, especially in areas with poor medical facilities. […] During IRT therapy, XLA patients may experience local side effects such as tiredness, swelling, and erythema, but the symptoms can easily resolve within a few hours.

• #24 X-linked Agammaglobulinemia (Congenital Agammaglobulinemia, Bruton’s Agammaglobulinemia – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/x-linked-agammaglobulinemia-congenital-agammaglobulinemia-brutons-agammaglobulinemia/

  The most important treatment is to replace the patients absent immunoglobulin. There are two forms of effective IgG replacement therapy: intravenous immunoglobulin G, subcutaneous immunoglobulin G. […] The most important treatment is to replace the patients absent immunoglobulin. There are two forms of effective IgG replacement therapy. Commercial preparations of immunoglobulin contain only IgG, thus there are theoretical reasons that the replacement IgG is not as good as producing our own immunoglobulin. First, it lacks IgA and thus is not as effective in mucosal immunity as the patients own production of immunoglobulin would be. Second, it is passive immunity and offers no active response to an invading microorganism with production of high-titer specific antibody. […] In addition to immunoglobulin replacement therapy, antibiotics should be used for the early treatment of bacterial infections.

• #25 X-Linked Agammaglobulinemia

  https://www.aaaai.org/conditions-treatments/primary-immunodeficiency-disease/x-linked-agammaglobulinemia

  There is no cure for XLA, but the condition can be successfully treated. Immunoglobulin replacement therapy is a life-long and life-saving treatment that restores some of the missing antibodies. […] In addition, some people benefit from a daily course of oral antibiotics to prevent or treat infections. […] Most individuals with XLA who receive immunoglobulin on a regular basis can lead relatively normal lives.

• #26 X-linked agammaglobulinemia // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/x-linked-agammaglobulinemia

  There’s no cure for XLA. Treatment aims at boosting the immune system to prevent infections. There also is quick treatment for infections as they happen. […] Medicines to treat XLA include: […] Gammaglobulin. This is a type of protein found in blood that contains antibodies against infections. It’s put into a vein, called infusion, every 2 to 4 weeks or given with weekly shots. […] Antibiotics. Some people with XLA take antibiotics all the time to prevent infections. Others take antibiotics for bacterial infections longer than do people without XLA. […] Your healthcare professional likely will suggest that you have follow-up visits every 6 to 12 months to screen for complications of XLA. You’ll also likely be told to not get live vaccines, such as live polio, measles-mumps-rubella or chickenpox vaccines.

• #27 X-Linked Agammaglobulinemia: Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/24955-x-linked-agammaglobulinemia

  Treatment for XLA includes antibody infusions. […] Theres no cure for XLA. But treatments can help you or your child avoid serious illness. They include: […] Replacement immunoglobulins (RIgG). Your healthcare provider gives you donor antibodies in a vein. Youll need this treatment at least once per month. […] Proactive treatment of infections. Your provider will treat bacterial infections with antibiotics as soon as they think youre sick. […] Avoiding live vaccinations. People with XLA cant get live vaccines. These can make you sick or even be fatal. This includes the MMR, chickenpox (varicella) and oral polio vaccines. […] People with XLA need treatment for the rest of their lives so theyre less vulnerable to illness. Theyll need to work closely with their healthcare provider to treat any illnesses as soon as possible.

• #28 Agammaglobulinemia: X-linked (XLA) and autosomal recessive (ARA) | Immune Deficiency Foundation

  https://primaryimmune.org/understanding-primary-immunodeficiency/types-of-pi/agammaglobulinemia-x-linked-and-autosomal

  At this time, the only treatment for individuals with agammaglobulinemia is immunoglobulin (Ig) replacement therapy. There currently is no cure for XLA, but there has been promising research regarding gene therapy for XLA, which is still in the pre-clinical stage. Ig replacement therapy for those with agammaglobulinemia replenishes some of the antibodies that they are lacking. The antibodies are supplied in the form of Ig, also known as gamma globulins or IgG. This Ig replacement therapy can be given directly into the bloodstream (intravenously) or under the skin (subcutaneously). […] The varying types of Ig replacement therapy contain antibodies that substitute for the antibodies that the individual cannot make themselves. These products contain antibodies to a wide variety of germs and are purified from the blood of healthy donors. Ig is particularly effective in preventing the spread of infections into the bloodstream and to deep body tissues or organs. Some people may also need daily oral antibiotics to protect them from infection or to treat chronic sinusitis or chronic bronchitis.

• #29 X-Linked (Bruton) Agammaglobulinemia Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1050956-treatment

  No curative therapy exists for X-linked agammaglobulinemia (XLA), or Bruton agammaglobulinemia. Treatment for XLA is IVIG. Typical doses are 400-600 mg/kg/mo given every 3-4 weeks. Doses and intervals can be adjusted based on individual clinical responses. Therapy should begin at age 10-12 weeks. Maintenance of an IgG trough level of 500-800 mg/dL is recommended. Therapy should be started at age 10-12 weeks. Currently, no evidence supports that one particular brand or route of administration (IV vs SC) is better than the other. […] Antibiotics, such as amoxicillin and amoxicillin/clavulanate, are administered for common sinopulmonary infections. Pending culture sensitivities, intravenous ceftriaxone may be used for chronic infections, pneumonia, or sepsis. […] Bronchodilators, steroid inhalers, and regular pulmonary function tests (at least 3-4 times a year) may be a required part of therapy in addition to antibiotics.

• #30 X-linked Agammaglobulinemia (Congenital Agammaglobulinemia, Bruton’s Agammaglobulinemia – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/x-linked-agammaglobulinemia-congenital-agammaglobulinemia-brutons-agammaglobulinemia/

  Optimal patient management involves a number of strategies. […] First and foremost is replacement immunoglobulin therapy. Whether the patient is treated with intravenous or subcutaneous IgG, the aim is to maintain his trough level (the level immediately before his next treatment) of IgG above 500mg/dL and/or an increment of 400mg above his pretreatment level. Monitoring trough IgG levels monthly in the first few months after initiating IgG replacement therapy and semi-annually thereafter can be very helpful in deciding dose and frequency of replacement therapy. Importantly, if the clinical response in terms of infection is not satisfactory, then increasing the dose of IgG may be desirable. […] Antibiotics should be used early in the course of any possible bacterial infection. […] Finally, the patients family should be instructed in the way in which the disease is inherited (X-linked) and the implications of that form of inheritance on future pregnancies of his parents and on the carrier status of sisters, maternal aunts and maternal cousins. When patient reaches an appropriate age, he should be counseled as to the risk of his daughters being a carrier (100%) and his sons being affected (0%)

• #31 Immunodeficiency Search

  https://www.immunodeficiencysearch.com/x-linked-agammaglobulinemia

  Immunoglobulin replacement therapy is the cornerstone of therapy for XLA patients. […] Replacement of serum IgG with monthly IVIG or weekly subcutaneous (SC) Ig is the cornerstone of therapy. Typical replacement is started with 400-600mg/kg of IVIG every 4 weeks or 100-150mg/kg of SCIg every week. Trough IgG levels should be checked after 5 IVIG doses. It is clear that patients who maintain trough IgG levels above 700-900mg/dl have fewer infectious complications. SCIg is ideal for patients who benefit from maintaining steady serum levels of immunoglobulins or who are unable to tolerate IVIG due to adverse side effects (headache, chills, nausea, thrombotic events). […] The addition of prophylactic antibiotics can be considered in patients who continue to have infections despite appropriate immunoglobulin replacement. Two sample prophylaxis regimens are listed below: 1. Amoxicillin 20mg/kg divided twice daily. Maximum of 500mg twice daily. 2. Azithromycin 10mg/kg once weekly. Maximum of 1 gram once weekly.

• #32 Agammaglobulinemia: X-linked (XLA) and autosomal recessive (ARA) | Immune Deficiency Foundation

  https://primaryimmune.org/understanding-primary-immunodeficiency/types-of-pi/agammaglobulinemia-x-linked-and-autosomal

  At this time, the only treatment for individuals with agammaglobulinemia is immunoglobulin (Ig) replacement therapy. There currently is no cure for XLA, but there has been promising research regarding gene therapy for XLA, which is still in the pre-clinical stage. Ig replacement therapy for those with agammaglobulinemia replenishes some of the antibodies that they are lacking. The antibodies are supplied in the form of Ig, also known as gamma globulins or IgG. This Ig replacement therapy can be given directly into the bloodstream (intravenously) or under the skin (subcutaneously). […] The varying types of Ig replacement therapy contain antibodies that substitute for the antibodies that the individual cannot make themselves. These products contain antibodies to a wide variety of germs and are purified from the blood of healthy donors. Ig is particularly effective in preventing the spread of infections into the bloodstream and to deep body tissues or organs. Some people may also need daily oral antibiotics to protect them from infection or to treat chronic sinusitis or chronic bronchitis.

• #33 Orphanet: X-linked agammaglobulinemia

  https://www.orpha.net/en/disease/detail/47

  There is no curative treatment for XLA but good disease control can be achieved through consistent gammaglobulin therapy. This can be given intravenously (400-600 mg/kg every 3 to 4 weeks) or subcutaneously (100 mg/kg every week). Therapy should be started as early as possible. Some immunologists advocate chronic prophylactic antibiotics and treatment of acute infections should be prolonged and at maximal doses of antibiotics.

• #34 Agammaglobulinemia: X-linked (XLA) and autosomal recessive (ARA) | Immune Deficiency Foundation

  https://primaryimmune.org/understanding-primary-immunodeficiency/types-of-pi/agammaglobulinemia-x-linked-and-autosomal

  People with antibody deficiency with absent B cells should not receive any live viral vaccines, such as live polio, the measles, mumps, rubella (MMR) vaccine, the chicken pox vaccine, the rotavirus vaccine, yellow fever, live typhoid, or the live shingles vaccine. Although uncommon, it is possible that live vaccines, particularly the oral polio vaccine, in people with agammaglobulinemia can transmit the diseases that they were designed to prevent. […] Individuals with antibody deficiency with absent B cells should receive the yearly influenza (flu) vaccine. Ig replacement therapy may interfere with the response to a vaccine; therefore, individuals should contact their healthcare provider prior to receiving any vaccination. It is also important for family members and close contacts of people with antibody deficiency with absent B cells to be vaccinated in order to provide them with a level of protection called herd immunity or community immunity.

• #35 X-linked agammaglobulinemia // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/x-linked-agammaglobulinemia

  There’s no cure for XLA. Treatment aims at boosting the immune system to prevent infections. There also is quick treatment for infections as they happen. […] Medicines to treat XLA include: […] Gammaglobulin. This is a type of protein found in blood that contains antibodies against infections. It’s put into a vein, called infusion, every 2 to 4 weeks or given with weekly shots. […] Antibiotics. Some people with XLA take antibiotics all the time to prevent infections. Others take antibiotics for bacterial infections longer than do people without XLA. […] Your healthcare professional likely will suggest that you have follow-up visits every 6 to 12 months to screen for complications of XLA. You’ll also likely be told to not get live vaccines, such as live polio, measles-mumps-rubella or chickenpox vaccines.

• #36 X-linked agammaglobulinemia medical therapy – wikidoc

  https://wikidoc.org/index.php/X-linked_agammaglobulinemia_medical_therapy

  Subcutaneous treatment (SCIg) was recently approved by the FDA, which is recommended in cases of severe adverse reactions to the IVIg treatment. […] Antibiotics are another common supplementary treatment. Local antibiotic treatment (drops, lotions) are preferred over systemic treatment (pills) for long term treatment, if possible. […] One of the future prospects of XLA treatment is gene therapy, which could potentially cure XLA. Gene therapy technology is still in its infancy and may cause severe complications such as cancer and even death. Moreover, the long term success and complications of this treatment are, as yet, unknown. […] It is not recommended and dangerous for XLA patients to receive live attenuated vaccines such as live polio, or the measles, mumps, rubella (MMR vaccine). Special emphasis is given to avoiding the oral live attenuated SABIN-type polio vaccine that has been reported to cause polio to XLA patients. Furthermore, it is not known if active vaccines in general have any beneficial effect on XLA patients as they lack normal ability to maintain immune memory.

• #37 Agammaglobulinemia: X-linked (XLA) and autosomal recessive (ARA) | Immune Deficiency Foundation

  https://primaryimmune.org/understanding-primary-immunodeficiency/types-of-pi/agammaglobulinemia-x-linked-and-autosomal

  People with antibody deficiency with absent B cells should not receive any live viral vaccines, such as live polio, the measles, mumps, rubella (MMR) vaccine, the chicken pox vaccine, the rotavirus vaccine, yellow fever, live typhoid, or the live shingles vaccine. Although uncommon, it is possible that live vaccines, particularly the oral polio vaccine, in people with agammaglobulinemia can transmit the diseases that they were designed to prevent. […] Individuals with antibody deficiency with absent B cells should receive the yearly influenza (flu) vaccine. Ig replacement therapy may interfere with the response to a vaccine; therefore, individuals should contact their healthcare provider prior to receiving any vaccination. It is also important for family members and close contacts of people with antibody deficiency with absent B cells to be vaccinated in order to provide them with a level of protection called herd immunity or community immunity.

• #38 Agammaglobulinemia: X-linked (XLA) and autosomal recessive (ARA) | Immune Deficiency Foundation

  https://primaryimmune.org/understanding-primary-immunodeficiency/types-of-pi/agammaglobulinemia-x-linked-and-autosomal

  People with antibody deficiency with absent B cells should not receive any live viral vaccines, such as live polio, the measles, mumps, rubella (MMR) vaccine, the chicken pox vaccine, the rotavirus vaccine, yellow fever, live typhoid, or the live shingles vaccine. Although uncommon, it is possible that live vaccines, particularly the oral polio vaccine, in people with agammaglobulinemia can transmit the diseases that they were designed to prevent. […] Individuals with antibody deficiency with absent B cells should receive the yearly influenza (flu) vaccine. Ig replacement therapy may interfere with the response to a vaccine; therefore, individuals should contact their healthcare provider prior to receiving any vaccination. It is also important for family members and close contacts of people with antibody deficiency with absent B cells to be vaccinated in order to provide them with a level of protection called herd immunity or community immunity.

• #39 X-Linked (Bruton) Agammaglobulinemia Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1050956-treatment

  Special concerns for patients with XLA arise preceding surgery. In this situation, intravenous immunoglobulin (IVIG) is preoperatively administered to prevent infection. Live vaccines must be withheld. […] Patients with XLA should follow their normal diet supplemented by a multivitamin. No dietary limitations are specific for XLA, although a low-fat diet may be needed for patients with inflammatory bowel disease. […] Patients with XLA have no specific physical limitations. Not smoking or not being exposed to smoke is strongly recommended for patients because of the increased risk of sinopulmonary infection. […] Patients with XLA are treated well medically as outpatients. Treatments with IVIG and necessary antibiotics for infections are all provided on an outpatient basis. Most tests and evaluations can be performed and most medications can be administered on an outpatient basis.

• #40 X-Linked Agammaglobulinemia (XLA) – AmeriPharma® Specialty Care

  https://ameripharmaspecialty.com/other-health-conditions/x-linked-agammaglobulinemia/

  The first and foremost goal is to protect patients from getting bacterial infections by maintaining good hygiene (frequent hand washing) and drinking treated water. […] Immunoglobulin replacement therapy (IRT) is a standard, lifelong, and life-saving treatment for XLA. IRT not only boosts the patient’s immune system but also improves the patient’s survival rate and quality of life by providing the missing immunoglobulins in the body. […] Intravenous immunoglobulin (IVIG) therapy is administered in the veins every 3 to 4 weeks. […] An alternative to IVIG therapy, subcutaneous immunoglobulin therapy (SCIG), may be chosen as an option due to IVIG adverse reactions or difficulty with IV access. […] Another alternative to IVIG therapy is intramuscular immunoglobulin therapy. […] IRT therapy is prepared from a donor pool; it does not provide immunity to unexposed pathogens.

• #41 X-Linked (Bruton) Agammaglobulinemia Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1050956-treatment

  No curative therapy exists for X-linked agammaglobulinemia (XLA), or Bruton agammaglobulinemia. Treatment for XLA is IVIG. Typical doses are 400-600 mg/kg/mo given every 3-4 weeks. Doses and intervals can be adjusted based on individual clinical responses. Therapy should begin at age 10-12 weeks. Maintenance of an IgG trough level of 500-800 mg/dL is recommended. Therapy should be started at age 10-12 weeks. Currently, no evidence supports that one particular brand or route of administration (IV vs SC) is better than the other. […] Antibiotics, such as amoxicillin and amoxicillin/clavulanate, are administered for common sinopulmonary infections. Pending culture sensitivities, intravenous ceftriaxone may be used for chronic infections, pneumonia, or sepsis. […] Bronchodilators, steroid inhalers, and regular pulmonary function tests (at least 3-4 times a year) may be a required part of therapy in addition to antibiotics.

• #42 X-linked agammaglobulinemia (XLA) – Children’s Health Immunology

  https://www.childrens.com/specialties-services/conditions/xla

  If your child is diagnosed with XLA, they will be treated with immunoglobulin IgG (antibodies) therapy on a regular basis for the rest of his life. IgG therapy can be given through a catheter in your childs vein (intravenous; IVIG) or subcutaneously (SCIG). The decision to use one or the other depends on whats best for your child and your family. There is currently no cure for XLA. […] Children with XLA should be followed at the center. If your child develops an infection, antibiotics can treat the infection. Some patients with XLA may have complications including gastrointestinal problems that may require cooperative interaction with gastroenterology specialists.

• #43 X-Linked (Bruton) Agammaglobulinemia Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1050956-treatment

  No curative therapy exists for X-linked agammaglobulinemia (XLA), or Bruton agammaglobulinemia. Treatment for XLA is IVIG. Typical doses are 400-600 mg/kg/mo given every 3-4 weeks. Doses and intervals can be adjusted based on individual clinical responses. Therapy should begin at age 10-12 weeks. Maintenance of an IgG trough level of 500-800 mg/dL is recommended. Therapy should be started at age 10-12 weeks. Currently, no evidence supports that one particular brand or route of administration (IV vs SC) is better than the other. […] Antibiotics, such as amoxicillin and amoxicillin/clavulanate, are administered for common sinopulmonary infections. Pending culture sensitivities, intravenous ceftriaxone may be used for chronic infections, pneumonia, or sepsis. […] Bronchodilators, steroid inhalers, and regular pulmonary function tests (at least 3-4 times a year) may be a required part of therapy in addition to antibiotics.

• #44 X-Linked (Bruton) Agammaglobulinemia Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1050956-treatment

  Infliximab has been used with X-linked agammaglobulinemia in a patient with associated granulomatous small bowel enteropathy. […] Nutritional supplementation with multivitamins is recommended. […] The feasibility of using gene-corrected hematopoietic stem cells to complement the immune defects in mouse models has been studied. It may be propitious to initiate stem cell-based therapy for XLA using gene-corrected autologous hematopoietic stem cells. More recent efforts suggest restoring Bruton tyrosine kinase may be practical as a future therapeutic option. Human hematopoietic stem cell gene editing may be utilized to rescue B-cell development. […] Surgical intervention for X-linked agammaglobulinemia (XLA) is limited to severe acute infections or unresponsive chronic infections. The most common procedures involve treating patients with recurrent otitis by inserting tympanostomy tubes and treating patients with chronic sinusitis by surgical drainage. Hematopoietic stem cell transplantation may produce a complete cure. Treosulfan-based reduced toxicity hematopoietic stem cell transplantation may be a good option.

• #45

  https://turkjpediatr.org/article/view/794

  The loss of inflammatory regulation resulting from the absence of B-lymphocytes leads to a risk for autoimmune and autoinflammatory complications. There is no data on the use of Vedolizumab in patients with X-linked agammaglobulinemia (XLA) as well as children with another primary immunodeficiency (PID) diseases. […] Vedolizumab (Entyvio), a humanized monoclonal antibody 47 integrin-receptor antagonist, was commenced. After treatment with vedolizumab, his fever and abdominal pain attacks reduced, his total daily calorie intake increased and weight gain improved. He began to walk again and continued his school education properly. No side effects were observed in 18 months. This is the first immunocompromised child treated with vedolizumab. The symptoms of the patient receded and no side effect were seen during the treatment.

• #46 X-linked Agammaglobulinemia: diagnosis story

  https://3billion.io/blog/x-linked-agammaglobulinemia-diagnosis-story

  We have optimised his IVIG dose and frequency to 4-weekly intervals, and referred him to the gastroenterology team for the inflammatory bowel disease work-up and rheumatology team for the arthritis work-up. […] He was started on antibody treatment at only the age of 17 years. This treatment known as intravenous immunoglobulin (IVIG), was given at a frequency of 4 times a week for one year, but was forced to stop due to financial difficulties. […] At the age of 24, the IVIG was restarted at 4 to 6 week intervals intermittently with no regular follow-up.

• #47 X-linked agammaglobulinemia – Doctors and departments – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/x-linked-agammaglobulinemia/doctors-departments/ddc-20361640

  Researchers and doctors trained in immune system disorders, genetics and other conditions conduct basic and clinical research aimed at developing new treatments for XLA. […] Treatments under study include stem cell transplantation and gene therapy.

• #48 News: The Long and Winding Road to a CRISPR Gene Therapy for X-Linked Agammaglobulinemia – CRISPR Medicine

  https://crisprmedicinenews.com/news/the-long-and-winding-road-to-a-crispr-gene-therapy-for-x-linked-agammaglobulinemia/

  New research on X-linked Agammaglobulinemia has led to the development of a potential gene therapy cure for this disease – or as Dr David Gray explains: How a simple gene therapy concept became a complicated game of 'whack-a-mole’. […] X-Linked Agammaglobulinemia (XLA) is a rare immunodeficiency disorder with a moderate treatment plan, but no cure. […] Treatment options are limited; while patients can receive regular antibody supplementation from healthy donors, there is no long-term treatment option or cure. […] With the advent of sophisticated gene-editing technology like CRISPR, gene therapy became a key avenue for XLA research. […] Gray hopes his CRISPR gene editing research will lead to a cure for X-linked Agammaglobulinemia and potentially pave the way for other gene therapies.

• #49 X-linked Agammaglobulinemia – Immunology; Allergic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/immunology-allergic-disorders/immunodeficiency-disorders/x-linked-agammaglobulinemia

  Treatment of X-linked agammaglobulinemia is immune globulin replacement therapy. […] Hematopoietic stem cell transplantation and gene therapy are also under investigation. […] Prompt use of adequate antibiotics for each infection is crucial; bronchiectasis may require frequent rotation of antibiotics. Live-virus vaccines are contraindicated.

• #50 X-Linked (Bruton) Agammaglobulinemia Treatment & Management: Medical Care, Surgical Care, Consultations

  https://emedicine.medscape.com/article/1050956-treatment

  Infliximab has been used with X-linked agammaglobulinemia in a patient with associated granulomatous small bowel enteropathy. […] Nutritional supplementation with multivitamins is recommended. […] The feasibility of using gene-corrected hematopoietic stem cells to complement the immune defects in mouse models has been studied. It may be propitious to initiate stem cell-based therapy for XLA using gene-corrected autologous hematopoietic stem cells. More recent efforts suggest restoring Bruton tyrosine kinase may be practical as a future therapeutic option. Human hematopoietic stem cell gene editing may be utilized to rescue B-cell development. […] Surgical intervention for X-linked agammaglobulinemia (XLA) is limited to severe acute infections or unresponsive chronic infections. The most common procedures involve treating patients with recurrent otitis by inserting tympanostomy tubes and treating patients with chronic sinusitis by surgical drainage. Hematopoietic stem cell transplantation may produce a complete cure. Treosulfan-based reduced toxicity hematopoietic stem cell transplantation may be a good option.

• #51 X-Linked (Bruton) Agammaglobulinemia: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1050956-overview

  Patients with XLA have survived into their late 40s. The prognosis is good as long as patients are diagnosed and treated early with regular intravenous gamma globulin therapy before the sequelae of recurrent infections appear. […] IVIG is responsible for increasing survival rates, with treatment beginning preferably before the patient is aged 5 years. […] Genetic counseling is recommended for the parents and female siblings of males who are affected. […] A combination of flow cytometry and Bruton tyrosine kinase gene analysis may be beneficial for carrier screening. […] Treosulfan-based reduced toxicity hematopoietic stem cell transplantation in X-linked agammaglobulinemia: A cost-effective alternative to long-term immunoglobulin replacement in developing countries. […] Hematopoietic stem cell gene editing rescues B-cell development in X-linked agammaglobulinemia. […] Splice-correction strategies for treatment of X-linked agammaglobulinemia. […] Biology and novel treatment options for XLA, the most common monogenetic immunodeficiency in man.

• #52 X-linked agammaglobulinemia – Wikipedia

  https://en.wikipedia.org/wiki/X-linked_agammaglobulinemia

  Antibiotics are another common supplementary treatment. Local antibiotic treatment (drops, lotions) are preferred over systemic treatment (pills) for long-term treatment, if possible. One of the future prospects of XLA treatment is gene therapy, which could potentially cure XLA. Gene therapy technology is still in its infancy and may cause severe complications such as cancer and even death. Moreover, the long-term success and complications of this treatment are, as yet, unknown.

• #53 X-linked agammaglobulinemia medical therapy – wikidoc

  https://wikidoc.org/index.php/X-linked_agammaglobulinemia_medical_therapy

  Subcutaneous treatment (SCIg) was recently approved by the FDA, which is recommended in cases of severe adverse reactions to the IVIg treatment. […] Antibiotics are another common supplementary treatment. Local antibiotic treatment (drops, lotions) are preferred over systemic treatment (pills) for long term treatment, if possible. […] One of the future prospects of XLA treatment is gene therapy, which could potentially cure XLA. Gene therapy technology is still in its infancy and may cause severe complications such as cancer and even death. Moreover, the long term success and complications of this treatment are, as yet, unknown. […] It is not recommended and dangerous for XLA patients to receive live attenuated vaccines such as live polio, or the measles, mumps, rubella (MMR vaccine). Special emphasis is given to avoiding the oral live attenuated SABIN-type polio vaccine that has been reported to cause polio to XLA patients. Furthermore, it is not known if active vaccines in general have any beneficial effect on XLA patients as they lack normal ability to maintain immune memory.

• #54 X-linked agammaglobulinemia (XLA) – Immunodeficiency UKAccessibilityIncrease TextDecrease TextGrayscaleHigh ContrastNegative ContrastLight BackgroundLinks UnderlineReadable FontReset

  https://www.immunodeficiencyuk.org/x-linked-agammaglobulinemia-xla/

  Immunoglobulin therapy is a highly effective therapy and those affected are able to live a normal healthy life if it is started early in childhood before any recurrent infections set in. […] Not at the present moment. […] There are no clinical trials of gene therapy for XLA at present. However, there is quite a bit of work ongoing in the laboratory and so trials may start in the not too distant future.

• #55

  https://link.springer.com/article/10.1007/s11882-014-0510-0

  X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disease caused by mutations in the gene coding for Brutons tyrosine kinase (BTK). […] Currently, there is no curative therapy for XLA, and the treatment instead consists of immunoglobulin substitution and frequent administration of antibiotics. […] Therefore, alternative strategies such as gene therapy remain valid. […] In this review, we will briefly discuss one such putative XLA therapy, BTK splice-correction, and its possible future applications. […] The strategy required to correct splicing defects depends on the nature of the mutation in question and is therefore a prime example of personalized medicine. […] The correction is most straightforward for defects caused by the activation of a cryptic splice site. […] Here, splice correction can be achieved by sterically blocking the access of splicing factors to either the cryptic splice sites themselves or nearby splicing enhancer sequences.

• #56

  https://link.springer.com/article/10.1007/s11882-014-0510-0

  In the simplest form, this can be done by administering short (15-25 nt) antisense oligonucleotides (ASOs). […] A number of splicing defects have been corrected with this methodology using in vivo models, including hematopoietic cell defects such as beta-thalassemia. […] The other main type of splicing defect, caused by the exclusion of bona fide exons, is a somewhat more challenging scenario. […] In those cases, it will be necessary to actively recruit splicing factors that promote splicing. […] One way is to use bi-functional oligonucleotides that have an antisense sequence targeting them to the desired site, as well as an unpaired tail sequence, that is able to bind splicing activator proteins. […] Another method for enhancing inclusion of skipped exons is to use modified components of the spliceosome itself.

• #57

  https://link.springer.com/article/10.1007/s11882-014-0510-0

  An even more exciting method is to use the spliceosomes capacity to catalyze splicing between two RNA molecules in what is known as trans-splicing. […] The aim of the second phase of the treatment would be to develop a potent humoral immunity against those infectious agents to which XLA patients are susceptible. […] Collectively, the suggested complementing treatment strategy should theoretically allow the maturation of B lymphocytes into plasma cells, generating long-term immune protection.

• #58 Hematopoietic Stem Cell Gene Therapy for X-linked Agammaglobulinemia – CIRM

  https://www.cirm.ca.gov/our-progress/awards/hematopoietic-stem-cell-gene-therapy-x-linked-agammaglobulinemia/

  We have initiated studies on gene editing for X-linked agammaglobulinemia (XLA). Initial studies are using a mouse model to test several potential therapeutic candidates and demonstrate disease-modifying activity. The final candidate will be further advanced to a Phase I/II clinical trial. […] We established methods to apply gene editing to mouse bone marrow stem cells in a model of X-linked Agammaglobulinemia (XLA) to perform studies to demonstrate disease modifying activity. We achieved successful engraftment of murine hematopoietic stem cells that had been gene edited to insert a normal murine BTK gene into the endogenous BTK locus. Transplant of the gene edited stem cells led to partial restoration of B cell production and antibody production, including specific antibody in response to immunization with test antigen. These studies provide evidence of disease modifying activity by gene editing and support future efforts to advance this therapy to clinical trials. […] XLA can be treated with chronic immunoglobulin replacement, but may be sub-optimal due to infections and inflammatory complications. Stem cell gene therapy may provide a curative one time treatment.

• #59

  https://link.springer.com/article/10.1007/s10875-024-01829-z

  Potential advances in management of XLA include measurement of kappa-deleting recombination excision circles (KREC) on newborn bloodspots to aid early diagnosis, and curative therapy by hematopoietic stem cell transplantation (HSCT) or, in development, gene editing therapy. […] Given the list of potential limitations in current therapy, supported by the data presented here and from others, serious consideration must be given to alternative management strategies such as HSCT. […] The two patients reported in these data with persistent norovirus infection, underwent successful HSCT under the premise that their persistent infection (necessitating total parental nutrition support) was not amenable to IgRT. […] We therefore suggest that HSCT can play in a role in the management of XLA, particularly in severe complications that are not amenable to IgRT and should be considered more readily in this patient population. Further work should assess the effectiveness of therapies current in development such as IgA/IgM enriched IgRT products and nebulised Ig.

• #60

  https://link.springer.com/article/10.1007/s10875-024-01829-z

  There are several studies demonstrating a proof of concept for the utility of gene therapy in XLA in BTK deficient mice spanning over a decade. However, despite these murine models, there are no clinical trials currently examining the use of gene therapy in human XLA patients, and these should be urgently developed.

• #61 X-Linked Agammaglobulinemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549865/

  X-linked agammaglobulinemia or XLA is a primary immunodeficiency disorder that prevents affected individuals from making antibodies and requires them to rely on lifelong immunoglobulin replacement therapy for survival. […] There is currently no cure for XLA; however, early management with immunoglobulin replacement therapy and antibiotics to prevent and treat infections. […] The optimal management of patients with XLA includes: Regular immunoglobulin replacement therapy, using intravenous or subcutaneous infusions; Therapeutic and prophylactic use of antibiotics to treat and prevent bacterial infections; Careful monitoring to manage reactions arising from immunoglobulin infusions, complications of infections, or the emergence of clinical disease (e.g., autoimmune, inflammatory, malignant); Support (nutritional, social, psychological, and educational); Counseling about the importance of receiving all available immunizations except for those containing live bacteria or viruses. […] Immunoglobulin replacement therapy has been used for decades and continues to be the core treatment modality for patients with XLA. […] Overall, an interprofessional team approach to the treatment of patients with XLA is the proper management methodology.

• #62 X-Linked Agammaglobulinemia – MD Searchlight

  https://mdsearchlight.com/genetic-disorders/x-linked-agammaglobulinemia/

  Lastly, patient support is important and may include nutritional, social, psychological, and educational help. […] Patients are also advised about the importance of getting all the vaccinations that dont contain live bacteria or viruses. […] When dealing with immunoglobulin therapy, there are several factors to consider. Both intravenous (IVIG) and subcutaneous (SCIG) therapies are suitable, and the decision between the two depends on the specifics of each patients situation. […] The side effects of immunoglobulin therapy can vary but are often not severe and only temporary. […] Despite being less frequent, delayed side effects are of greater concern. […] To avoid these reactions, a regimen that has previously been tolerated well by the patient, with attention to preparation and infusion speed, should be maintained.

• #63 X-linked agammaglobulinemia (XLA) – Children’s Health Immunology

  https://www.childrens.com/specialties-services/conditions/xla

  If your child is diagnosed with XLA, they will be treated with immunoglobulin IgG (antibodies) therapy on a regular basis for the rest of his life. IgG therapy can be given through a catheter in your childs vein (intravenous; IVIG) or subcutaneously (SCIG). The decision to use one or the other depends on whats best for your child and your family. There is currently no cure for XLA. […] Children with XLA should be followed at the center. If your child develops an infection, antibiotics can treat the infection. Some patients with XLA may have complications including gastrointestinal problems that may require cooperative interaction with gastroenterology specialists.

• #64 X-linked agammaglobulinemia – VALINTERMED treatment in Valencia

  https://valintermed.com/en/medlibrary/chromosomal-agammaglobulinemia/

  Treatment of X-linked agammaglobulinemia should be aimed at correcting immune function and preventing infectious diseases. Common treatments include: […] Immunoglobulin therapy, in which patients are given intravenous or oral forms of human immunoglobulin to replace missing antibodies. […] Pharmacological treatment may include antibiotics to control and prevent infections. […] Surgical treatment may be necessary in cases of complications associated with infections. […] Other treatments may include vaccinations against specific infections, although their effectiveness may be limited by immune deficiency. […] Treatment includes immunoglobulin therapy, antibiotics and possible surgical interventions in case of complications.

• #65 X-Linked (Bruton) Agammaglobulinemia: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1050956-overview

  Patients with XLA have survived into their late 40s. The prognosis is good as long as patients are diagnosed and treated early with regular intravenous gamma globulin therapy before the sequelae of recurrent infections appear. […] IVIG is responsible for increasing survival rates, with treatment beginning preferably before the patient is aged 5 years. […] Genetic counseling is recommended for the parents and female siblings of males who are affected. […] A combination of flow cytometry and Bruton tyrosine kinase gene analysis may be beneficial for carrier screening. […] Treosulfan-based reduced toxicity hematopoietic stem cell transplantation in X-linked agammaglobulinemia: A cost-effective alternative to long-term immunoglobulin replacement in developing countries. […] Hematopoietic stem cell gene editing rescues B-cell development in X-linked agammaglobulinemia. […] Splice-correction strategies for treatment of X-linked agammaglobulinemia. […] Biology and novel treatment options for XLA, the most common monogenetic immunodeficiency in man.

• #66 X-Linked Agammaglobulinemia – MD Searchlight

  https://mdsearchlight.com/genetic-disorders/x-linked-agammaglobulinemia/

  The prognosis for X-Linked Agammaglobulinemia (XLA) has significantly improved with advancements in medical treatment practices. If diagnosed early, individuals with XLA can have a better prognosis. […] With regular immunoglobulin replacement therapy to boost the immune system and prescribed antibiotics to treat or prevent infections, affected individuals can anticipate a normal quality of life and a life expectancy beyond the age of 40.

• #67 X-Linked Agammaglobulinemia in Children | Phoenix Children’s Hospital

  https://phoenixchildrens.org/specialties-conditions/x-linked-agammaglobulinemia-children

  Without antibody replacement, a child with this disease could die at an early age from severe infections. Some children who get chronic lung disease with widening and scarring of the airways (bronchiectasis) may have a shortened lifespan. But most children with X-linked agammaglobulinemia who are treated early can lead normal, active lives.

• #68 X-Linked Agammaglobulinemia in Children | Phoenix Children’s Hospital

  https://phoenixchildrens.org/specialties-conditions/x-linked-agammaglobulinemia-children

  Without antibody replacement, a child with this disease could die at an early age from severe infections. Some children who get chronic lung disease with widening and scarring of the airways (bronchiectasis) may have a shortened lifespan. But most children with X-linked agammaglobulinemia who are treated early can lead normal, active lives.

• #69 X-Linked Agammaglobulinemia | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/31430

  X-linked agammaglobulinemia or XLA is one of the most common pediatric primary immunodeficiencies that prevent affected individuals from making antibodies and requires lifelong immunoglobulin replacement therapy for survival. […] There is currently no cure for XLA; however, early management with immunoglobulin replacement therapy and antibiotics to prevent and treat infections. Although this lifelong avenue is costly, it has been the mainstay of treatment for the past fifty years. […] The optimal management of patients with XLA includes regular immunoglobulin replacement therapy, using intravenous or subcutaneous infusions, therapeutic and prophylactic use of antibiotics to treat and prevent bacterial infections, careful monitoring to manage reactions arising from immunoglobulin infusions, complications of infections, or the emergence of clinical disease, support (nutritional, social, psychological, and educational), and counseling about the importance of receiving all available immunizations except for those containing live bacteria or viruses. […] Immunoglobulin replacement therapy has been used for decades and continues to be the core treatment modality for patients with XLA. […] The current mainstay of treatment is with intravenous immunoglobulin.

• #70 Agammaglobulinemia: X-linked (XLA) and autosomal recessive (ARA) | Immune Deficiency Foundation

  https://primaryimmune.org/understanding-primary-immunodeficiency/types-of-pi/agammaglobulinemia-x-linked-and-autosomal

  At this time, the only treatment for individuals with agammaglobulinemia is immunoglobulin (Ig) replacement therapy. There currently is no cure for XLA, but there has been promising research regarding gene therapy for XLA, which is still in the pre-clinical stage. Ig replacement therapy for those with agammaglobulinemia replenishes some of the antibodies that they are lacking. The antibodies are supplied in the form of Ig, also known as gamma globulins or IgG. This Ig replacement therapy can be given directly into the bloodstream (intravenously) or under the skin (subcutaneously). […] The varying types of Ig replacement therapy contain antibodies that substitute for the antibodies that the individual cannot make themselves. These products contain antibodies to a wide variety of germs and are purified from the blood of healthy donors. Ig is particularly effective in preventing the spread of infections into the bloodstream and to deep body tissues or organs. Some people may also need daily oral antibiotics to protect them from infection or to treat chronic sinusitis or chronic bronchitis.

• #71

  https://link.springer.com/article/10.1007/s10875-024-01829-z

  X-linked agammaglobulinaemia (XLA), caused by mutations in BTK, is characterised by low or absent peripheral CD19+B lymphocytes and agammaglobulinaemia. The mainstay of treatment consists of immunoglobulin replacement therapy (IgRT). […] Despite modern therapy, most XLA patients continue to experience complications, most notably bronchiectasis, likely due to absence of IgA/M in current therapies, but lack of B lymphocytes may also lead to additional sequalae. These data strongly support the need for further research, particularly that of curative modalities including HSCT and gene therapy. […] Since the first case report, the foundation of treatment continues to be immunoglobulin replacement therapy (IgRT). […] However, there are concerns that despite modern IgRT, XLA patients continue to experience significant infectious and non-infectious complications.

• #72

  https://gtr.ukri.org/projects?ref=MR%2FS021930%2F1

  X-linked Agammaglobulineamia (XLA) is an inherited immunodeficiency affecting 1 in 250,000 births. Conventional therapy comprises life-long infusions of immunoglobulin but the cumulative cost is high and this is not available in some developing countries. Currently a safe and definitive treatment is lacking. This project will be a pre-clinical feasibility study to establish this technique for the treatment of XLA. The main aim of this project is to deliver a gene editing technique to be used in patients with X-linked Agammaglobulinemia (XLA). If successful this will lead to clinical trials of a gene-edited cell therapy which will be potentially curative. If this project is successful then it can be adapted for other immunological and haematological conditions. This project will assess the CRISPR-Cas system of gene editing to correct this mutation. This involves nucleofection of cells with the Cas 9 protein complexed with a guide RNA complementary to our chosen target. The project will involve engagement with patient groups including UKPIPS as well as the wider public through UCL’s Public Engagement Unit.

Zobacz więcej