SummaryAcquired 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.

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Catalytic antibodies are immunoglobulins endowed with enzymatic properties. Discovered in the second part of the 1980s, the enthusiasm they initially aroused was counterbalanced by the difficulty of their production and their low catalytic rates. Nevertheless, improvements in expression systems and engineering technologies, combined with various studies suggesting that catalytic antibodies play a role in the immune system, have opened the way to new applications for these proteins. Herein we review catalytic antibodies from a biotechnological point of view, focusing our study on the different production methods, expression systems and their potential clinical applications dedicated to these proteins.

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