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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-lymphocyte-associated 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 immuno-pathogenesis of AHA, with a special focus on the potential role played by antibodies endowed with proteolytic properties.

journal_name

Br J Haematol

journal_title

British journal of haematology

authors

Mahendra A,Padiolleau-Lefevre S,Kaveri SV,Lacroix-Desmazes S

doi

10.1111/j.1365-2141.2011.08890.x

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

3-12

issue

1

eissn

0007-1048

issn

1365-2141

journal_volume

156

pub_type

杂志文章,评审

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