The IgG autoimmune response in postpartum acquired hemophilia A targets mainly the A1a1 domain of FVIII

Summary. Background: Acquired hemophilia A (AHA) is a severe life‐threatening autoimmune disease due to the development of autoantibodies that neutralize the procoagulant activity of factor VIII (FVIII). In rare cases, AHA occurs in the postpartum period as a serious complication of an otherwise normal pregnancy and delivery. Due to its rarity, little is known about the features of the antibody response to FVIII in AHA. Objectives: Our study wanted to (i) determine the epitope specificity and the immunoglobulin (Ig) subclasses of anti‐FVIII autoantibodies in plasma samples from a large cohort of AHA patients, and (ii) compare the epitope specificity of anti‐FVIII autoantibodies in plasma samples from postpartum AHA and other AHA patients. Patients/Methods: Seventy‐three plasma samples from patients with postpartum AHA (n = 10) or associated with malignancies (n = 16) or autoimmune diseases (n = 11) or without underlying disease (n = 36) were analyzed with three multiplexed assays. Results and Conclusions: Our results showed a stronger response against the A1a1‐A2a2‐B fragments of FVIII and more specifically against the A1a1 domain in patients with postpartum AHA than in the other AHA groups (P < 0.01). Moreover, although IgG₄ was the predominant IgG subclass in all groups, anti‐A1a1‐A2a2‐B and anti‐A1a1 domain autoantibodies of the IgG₁ and IgG₃ subclasses were more frequently detected in postpartum AHA than in the other AHA groups. These findings support the involvement of the Th1‐driven response in the generation of autoantibodies in women with postpartum AHA compared with the other groups of AHA patients in whom production of Th2‐driven IgG₄ was predominant.