title: Pathogenesis of antiphospholipid syndrome: understanding the antibodies.
abstract: Antiphospholipid antibodies (aPL) are both diagnostic markers for, and pathogenic drivers of, antiphospholipid syndrome (APS). Although the presence of aPL is a necessary pre-condition, APS-associated clotting is seemingly triggered by an additional 'second hit', frequently related to innate inflammatory immune responses. β(2) glycoprotein I (β(2)GPI)-dependent aPL, the most important subset of these antibodies, mediate several--not necessarily alternative--thrombogenic mechanisms, mainly on the basis of their reactivity with β(2)GPI expressed on the membrane of cells that participate in the coagulation cascade. Recurrent pregnancy complications associated with aPL cannot be explained solely by thrombosis, and alternative pathogenic mechanisms have been reported. Although one in vivo model of fetal loss suggests a mechanism of aPL-mediated acute placental inflammation, other models and the histopathological examination of APS placentae do not support a widespread inflammatory signature. β(2)GPI-dependent aPL are thought to recognize their antigen on placental tissues, inhibit the growth and differentiation of trophoblasts, and eventually cause defective placentation. Why antibodies with similar antigen specificity produce different clinical manifestations is not clear. Characterization of the molecular basis of the pathogenic mechanisms involved, including the putative second hits and the role of complement activation, might offer an answer to this question.
authors.affiliation: Department of Internal Medicine, University of Milan, Via della Pace 9, 20122 Milan, Italy. pierluigi.meroni@ unimi.it
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Meroni
authors.forename: M Orietta
authors.initials: MO
authors.lastname: Borghi
authors.forename: Elena
authors.initials: E
authors.lastname: Raschi
authors.forename: Francesco
authors.initials: F
authors.lastname: Tedesco
mesh_terms: D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000209:etiology* / Q000276:immunology*; D005260:Female; D006801:Humans; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology* / Q000276:immunology*
chemical_list: D017152:Antibodies, Antiphospholipid