title: Pathogenesis of the antiphospholipid syndrome revisited: time to challenge the dogma.
abstract: For more than a decade the antiphospholipid syndrome (APS) has been reported to be caused mainly by antiphospholipid antibodies (aPL), which are not directed against phospholipids but against a complex of phospholipids and phospholipid binding proteins, so called cofactors (e.g. β2-glycoprotein I [β2GPI]). In fact, many researchers propose that the only relevant antigens in the APS are the cofactors themselves, with β2GPI being the most important. Antibodies that bind to phospholipids in a cofactor-independent manner are considered insignificant for the pathogenesis of the APS. We review the evidence for this current pathophysiologic concept and argue that it has never been proven and is now clearly no longer tenable. First, there is undisputable evidence that cofactor-independent aPL are pathogenic and present in the blood of APS patients. Second, available epidemiologic and clinical studies do not support a dominant pathogenic role for anti-β2GPI.
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medical Centre Mainz, Mainz, Germany.
authors.forename: K J
authors.initials: KJ
authors.lastname: Lackner
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medical Centre Mainz, Mainz, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Müller-Calleja
mesh_terms: D017152:Antibodies, Antiphospholipid / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D013923:Thromboembolism / Q000503:physiopathology; D053482:beta 2-Glycoprotein I / Q000276:immunology
chemical_list: D017152:Antibodies, Antiphospholipid; D053482:beta 2-Glycoprotein I
keywords: anticardiolipin cofactor; antiphospholipid antibodies; antiphospholipid syndrome; beta2-glycoprotein I; venous thrombosis