The IgG autoimmune response in postpartum acquired hemophilia A targets mainly the A1a1 domain of FVIII
Article first published online: 4 SEP 2012
© 2012 International Society on Thrombosis and Haemostasis
Journal of Thrombosis and Haemostasis
Volume 10, Issue 9, pages 1814–1822, September 2012
How to Cite
LAPALUD, P., ALI, T., CAYZAC, C., MATHIEU-DUPAS, E., LEVESQUE, H., PFEIFFER, C., BALICCHI, J., GRUEL, Y., BORG, J. Y., SCHVED, J. F., GRANIER, C. and LAVIGNE-LISSALDE, G. (2012), The IgG autoimmune response in postpartum acquired hemophilia A targets mainly the A1a1 domain of FVIII. Journal of Thrombosis and Haemostasis, 10: 1814–1822. doi: 10.1111/j.1538-7836.2012.04850.x
- Issue published online: 4 SEP 2012
- Article first published online: 4 SEP 2012
- Accepted manuscript online: 11 JUL 2012 11:28AM EST
- Received 18 April 2012, accepted 3 July 2012
- acquired hemophilia A;
- factor VIII;
- x-MAP technology
Summary. 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 IgG1 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.