The IgG autoimmune response in postpartum acquired hemophilia A targets mainly the A1a1 domain of FVIII.
J Thromb Haemost
; 10(9): 1814-22, 2012 Sep.
Article
in En
| MEDLINE
| ID: mdl-22784315
ABSTRACT
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 ANDCONCLUSIONS:
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Factor VIII
/
Immunoglobulin G
/
Postpartum Period
/
Alanine
/
Hemophilia A
Limits:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Middle aged
/
Pregnancy
Language:
En
Journal:
J Thromb Haemost
Journal subject:
HEMATOLOGIA
Year:
2012
Document type:
Article
Affiliation country:
Francia