Review of immune tolerance induction in hemophilia A
| Autor: | Sarah J Schep, Roger E. G. Schutgens, Krista Fischer, Marianne Boes |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities medicine.medical_specialty Allergy T-Lymphocytes 030204 cardiovascular system & hematology Adaptive Immunity Hemophilia A Immune tolerance 03 medical and health sciences Structure-Activity Relationship 0302 clinical medicine Immune system Isoantibodies hemic and lymphatic diseases Internal medicine Immune Tolerance Medicine Animals Humans Anti-FVIII antibodies Immune tolerance induction ( Peripheral tolerance induction B-Lymphocytes Hematology Factor VIII biology Blood Coagulation Factor Inhibitors business.industry Inhibitors medicine.disease Tolerance induction Oncology Immunology biology.protein Working mechanism Antibody business Complication 030215 immunology |
| Zdroj: | Blood Reviews, 32(4), 326. Churchill Livingstone |
| ISSN: | 0268-960X |
| Popis: | At first sight the bleeding disorder hemophilia A seems to have little in common with immune disorders, but immunology research intersects with other disciplines including hematology. Nowadays, the most important complication in the treatment of hemophilia A is the development of neutralizing antibodies (inhibitors) against exogenous administered factor VIII (FVIII), which occurs in approximately 30% of all patients with severe hemophilia A. This antibody response renders FVIII replacement therapy ineffective, thereby increasing the risk for uncontrollable bleeding and morbidity, decreasing quality of life and increasing healthcare costs. The only proven effective therapy to eradicate these inhibitors is immune-based. Using a protocol called "immune tolerance induction" (ITI), the repeated and frequent administration of FVIII under non-inflammatory conditions downregulates the established antibody response and induces immune tolerance. There has been progress in research clarifying the mechanisms that mediate tolerance induction using ITI, both from patient studies and from research in cell culture and animal-based models. Peripheral tolerance induction to FVIII involves the apoptosis of antigen-specific B-memory cells, anergy induction in antigen-specific effector T-cells (Teff), induction of regulatory T-cells (Treg) and the formation of anti-idiotypic antibodies. In this review hemophilia A will be used as an example to discuss current concepts of tolerance induction as they are applied in patient care. Where possible, we will extrapolate tolerance findings in hemophilia A to related pathways known to affect auto-immune disorders or allergy. |
| Databáze: | OpenAIRE |
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