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Evidences for Heterogeneity of the Obstetrical Antiphospholipid Syndrome: thrombosis can be Critical for Antiphospholipid-Induced Pregnancy Loss.
MedLine Citation:
PMID:  21848640     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background: Antiphospholipid antibodies are associated with thrombosis and repeated pregnancy losses during the antiphospholipid syndrome. Several experimental evidences indicate that purified antiphospholipid antibodies are directly responsible for inflammation-induced pregnancy losses, or for disruption of the Annexin A5 shield at the trophoblastic interface. We previously showed that passive transfer of CIC15, a monoclonal antiphospholipid antibody binding to cardiolipin and annexin A5 and that was isolated from a patient with primary antiphospholipid syndrome, induces fetal resorptions in pregnant mice. Objectives: to investigate the mechanisms of CIC15-induced pregnancy loss. Methods/results: We show that CIC15 induces fetal loss through a new mechanism likely related to a procoagulant activity. The time course is different from previously described models, histological analysis shows that the placentas are devoid of any sign of inflammation but display some images of thrombotic events. Despite these differences, the CIC15 and "inflammatory" models share some similarities: lack of FcgammaRI/III dependency, and efficacy of heparin in preventing fetal losses. However this latter observation is here mostly due to anticoagulation rather than complement inhibition because fondaparinux sodium and hirudin show similar efficiency. In vitro, CIC15 enhances cardiolipin-induced prothrombinase assay. Finally, using combination of surface sensitive methods, we show that although it binds complexes of Cardiolipin-annexin A5, CIC15 is not able to disrupt the 2D ordered arrays of annexin A5. Conclusions: This human monoclonal antibody is responsible for pregnancy loss through a new mechanism involving thrombosis. This mechanism adds to the heterogeneity of the obstetrical antiphospholipid syndrome.
Authors:
V Poindron; R Berat; A M Knapp; F Toti; F Zobairi; A S Korganow; M P Chenard; C Gounou; J L Pasquali; A Brisson; T Martin
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-17
Journal Detail:
Title:  Journal of thrombosis and haemostasis : JTH     Volume:  -     ISSN:  1538-7836     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-8-18     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:
Copyright © 2011 International Society on Thrombosis and Haemostasis.
Affiliation:
National Referral Center for Systemic Autoimmune Diseases, Clinical Immunology Department, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Université de Strasbourg and CNRS UPR 9021, 67091 Strasbourg Molecular Imaging and NanoBioTechnology, IECB, CBMN UMR-5248 CNRS Université de Bordeaux-1 ENITAB, Avenue des Facultés, F-33402 Talence Pathology Department, Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg, Strasbourg U. 770 INSERM, Hôpital de Bicêtre, France; Université Paris-Sud-11, Faculté de Médecine, Le Kremlin-Bicêtre Université de Strasbourg, Faculté de Médecine, Institut d'Hématologie & Immunologie, Strasbourg, France.
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