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:  Publisher    
Abstract/OtherAbstract:
Background: Acquired hemophilia A (AHA) is a severe life-threatening autoimmune disease due to the development of autoantibodies that neutralize the pro-coagulant 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, 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), 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 IgG(4) was the predominant IgG subclass in all groups, anti-A1a1-A2a2-B and anti-A1a1 domain autoantibodies of the IgG(1) and IgG(3) 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 to the other groups of AHA patients in whom production of Th2-driven IgG(4) was predominant. © 2012 International Society on Thrombosis and Haemostasis.
Authors:
P Lapalud; T Ali; C Cayzac; E Mathieu-Dupas; H Levesque; C Pfeiffer; J Balicchi; Y Gruel; Jy Borg; Jf Schved; C Granier; G Lavigne-Lissalde
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-11
Journal Detail:
Title:  Journal of thrombosis and haemostasis : JTH     Volume:  -     ISSN:  1538-7836     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101170508     Medline TA:  J Thromb Haemost     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 International Society on Thrombosis and Haemostasis.
Affiliation:
SysDiag UMR3145 CNRS/BioRad, Montpellier, France Obstetrics Department, Damascus University Hospital, Syria Internal Medicine, Rouen University Hospital, France Inserm U1096, Rouen, France Department of Hematology-Hemostasis, University François Rabelais, Tours, France GICC UMR CNRS 7252, University François Rabelais, Tours, France Hematology Department, Rouen University Hospital, France Regional Hemophilia Treatment Centre, University Hospital St Eloi, Montpellier, France University Montpellier 1, Montpellier, France.
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