Genetic markers in acquired haemophilia

Abstract

Acquired haemophilia (AH) is a rare autoimmune bleeding disorder, which arises as a result of the spontaneous production of autoantibodies against endogenous factor VIII. The breakdown in immune tolerance is thought to be a result of a combination of genetic and environmental factors. Both human leucocyte antigen (HLA) and cytotoxic T lymphocyte antigen 4 (CTLA-4) play an important role in the maintenance of peripheral T-cell tolerance. A higher frequency of HLA class II alleles and single nucleotide polymorphisms of the CTLA-4 gene have been observed in some autoimmune diseases and severe haemophilia A. In 57 patients with AH, significantly higher frequencies of the HLA class II alleles DRB*16 [odds ratio (OR) 10.2] and DQB1*0502 (OR 2.5) have been detected when compared with controls. The CTLA-4 + 49 G allele has also presented with a significantly higher frequency in the same cohort of patients with AH (OR 2.17). This observation was mainly because of a higher frequency of the CTLA-4 + 49 G allele in female patients. These findings suggest that immune response genes may contribute to the development of anti-factor VIII autoantibodies in AH.