Do proteolytic antibodies complete the panoply of the autoimmune response in acquired haemophilia A?
Abstract
Acquired haemophilia A (AHA) is a rare bleeding disorder
characterized by the sudden generation of autoantibodies against
factor VIII (FVIII) in individuals with no previous history of
abnormal haemostasis. Understanding the pathogenesis of this
disease has been hampered by the rarity of the patients and the
difficulty in obtaining biological material from untreated
patients. Still, progress has been made recently in understanding
the pathogenesis of AHA. In particular, the importance of CD4+
T cells in AHA development has been documented and the
epitopes targeted by T cells on FVIII have been delineated.
Accordingly, a polymorphism in the cytotoxic T-lymphocyteassociated protein 4 gene (CTLA4), known to participate in the
regulation of CD4+ T-cell responses, and a preferential usage of
certain human leukocyte antigen class II haplotypes, have been
associated with the disease. Recent findings have documented
the presence of immunoglobulin G (IgG) with proteolytic
activity against FVIII and factor IX (FIX) in patients with AHA.
While FVIII-hydrolysing IgG has been shown to inactivate
FVIII, FIX-hydrolysing IgG from AHA patients activate FIX in
vitro. Here, we describe the latest findings on the immunopathogenesis of AHA, with a special focus on the potential role
played by antibodies endowed with proteolytic properties.