Document Detail


The IgG autoimmune response in postpartum acquired hemophilia A targets mainly the A1a1 domain of FVIII.
MedLine Citation:
PMID:  22784315     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 IgG(1) 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.
Authors:
P Lapalud; T Ali; C Cayzac; E Mathieu-Dupas; H Levesque; C Pfeiffer; J Balicchi; Y Gruel; J Y Borg; J F Schved; C Granier; G Lavigne-Lissalde
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of thrombosis and haemostasis : JTH     Volume:  10     ISSN:  1538-7836     ISO Abbreviation:  J. Thromb. Haemost.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-04     Completed Date:  2013-02-07     Revised Date:  2014-07-31    
Medline Journal Info:
Nlm Unique ID:  101170508     Medline TA:  J Thromb Haemost     Country:  England    
Other Details:
Languages:  eng     Pagination:  1814-22     Citation Subset:  IM    
Copyright Information:
© 2012 International Society on Thrombosis and Haemostasis.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Alanine / genetics*
Factor VIII / genetics*
Female
Hemophilia A / immunology*
Humans
Immunoglobulin G / immunology*
Middle Aged
Postpartum Period*
Pregnancy
Chemical
Reg. No./Substance:
0/Immunoglobulin G; 9001-27-8/Factor VIII; OF5P57N2ZX/Alanine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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