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Updating on the Pathogenic Mechanisms 5 of the Antiphospholipid Antibodies-Associated Pregnancy Loss

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Abstract

Anti-phospholipid antibodies (aPL) are risk factor for recurrent pregnancy loss and obstetrical complications. The mechanisms of aPL-mediated pregnancy failure are still a matter of research. Although aPL are associated with thrombosis, thrombotic events cannot explain all the miscarriages. There is evidence for a direct in vitro aPL effect on the trophoblast as shown by their binding; reduction of proliferation, human chorionic gonadotrophin release, in vitro invasiveness, adhesion molecule expression; and increased apoptosis. Such a direct reactivity is supported by the expression of beta2 glycoprotein (β2GP) I on trophoblast cell membranes. aPL/anti-β2GPI antibodies also bind to human decidual/endometrial cells in vitro and induce a pro-inflammatory phenotype. APL-mediated inflammatory processes at the placental level are apparently responsible for fetal loss at least in animal models. Both complement activation and pro-inflammatory cytokine/chemokine secretion have been shown to play a role. More recently, complement-induced tissue factor expression on infiltrating neutrophils was described as an additional pathogenic mechanisms mediated by aPL. As a whole, these findings do suggest that aPL may induce a defective placentation by acting at different levels without involving necessarily thrombotic events.

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Acknowledgment

This study has been supported in part by Ricerca Corrente IRCCS Istituto Auxologico Italiano (project APS 20C401 to P.L.M.) and to PRIN (prot. 2006061255 to P.L.M.). The authors would like to thank Dr. Paola Panzeri for her assistance in revising the manuscript.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Milan, Milan, Italy

    Pier Luigi Meroni, Maria Gerosa, Elena Raschi, Silvia Scurati, Claudia Grossi & Maria O. Borghi

  2. Allergy, Clinical Immunology and Rheumatology Unit, IRCCS Istituto Auxologico Italiano, Via Spagnoletto, 3, 20149, Milan, Italy

    Pier Luigi Meroni

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  1. Pier Luigi Meroni
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Correspondence to Pier Luigi Meroni.

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Meroni, P.L., Gerosa, M., Raschi, E. et al. Updating on the Pathogenic Mechanisms 5 of the Antiphospholipid Antibodies-Associated Pregnancy Loss. Clinic Rev Allerg Immunol 34, 332–337 (2008). https://doi.org/10.1007/s12016-007-8055-9

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