Immune System‐Related Genetic Risk Factors for Inhibitory Antibody Development in Patients With Hemophilia: Reviewing an Old Problem From a New Perspective—A Narrative Review

Background and Aims Hemophilia A and B are two of the most common bleeding disorders. Genetic risk factors are associated with the development of autoantibodies released in hemophilia patients against alternative factors and are the most important problems associated with the care of these patients. Objective In this study, we reviewed genetic risk factors related to the immune system in patients with hemophilia A and B who developed inhibitory antibodies against factors 8 or 9. Methods This study is based on the PubMed database and Google Scholar search engine information (2016–2025) in English using the terms “inhibitors”, “inhibitory antibodies”, “immune system”, and “hemophilia”. Results Studies have shown that multiple genetic factors (CTLA‐4, PTPN22, and cytokine polymorphisms) increase the risk of producing an inhibitor against alternative factors (8 and 9) in patients with severe hemophilia. Conclusions The presence of inhibitory antibodies in patients with severe hemophilia may be associated with immune system‐related genetic risk factors, and several studies have shown that in most cases, immune system‐related polymorphisms (rs2476601 PTPN22, rs2069812 IL5, and rs1800629 TNF‐α) produce autoimmune antibodies or exacerbate them.