Pathophysiological insights into the antiphospholipid syndrome

Summary

The antiphospholipid syndrome (APS) is characterized by venous and/or arterial thrombosis and severe pregnancy morbidity in presence of antiphospholipid antibodies (aPL). While there is compelling evidence that aPL cause the clinical manifestations of APS, the underlying mechanisms are still a matter of scientific debate. This is mainly related to the broad heterogeneity of aPL. There are three major types of aPL: The first one binds to (anionic) phospholipids, e.g. cardiolipin, in absence of other factors (cofactor independent aPL). The second type binds to phospholipids only in presence of protein cofactors, e.g. ß2-glycoprotein I (ß2GPI) (cofactor dependent aPL). The third type binds to cofactor proteins directly without need for phospholipids. It is widely believed that cofactor independent aPL (type 1) are associated with infections and, more importantly, non-pathogenic, while pathogenic aPL belong to the second and in particular to the third type. This view, in particular with regard to type 1 aPL, has not been undisputed and novel research data have shown that it is in fact untenable. We summarize the available data on the pathogenetic role of aPL and the implications for diagnosis of APS and future research.

Zusammenfassung

Das Antiphospholipidsyndrom (APS) ist gekennzeichnet durch venöse und/oder arterielle Thrombosen oder schwerwiegende Schwangerschaftskomplikationen in Anwesenheit von Antiphospholipid-Antikörpern (aPL). Während es überzeugende Belege dafür gibt, dass aPL die klinischen Manifestationen des APS verursachen, sind die zugrundeliegenden Mechanismen – hauptsächlich aufgrund der Heterogenität der aPL – noch wissenschaftlich umstritten. Man kann drei hauptsächliche aPL-Typen unterscheiden: Der erste Typ bindet (anionische) Phospholipide wie z. B. Cardiolipin in Abwesenheit anderer Faktoren (Kofaktor-unabhängige aPL). Der zweite Typ bindet Phospholipide nur in Anwesenheit von Proteinkofaktoren wie z. B. b2-Glykoprotein I (ß2GPI) (Kofaktor-abhängige aPL). Der dritte Typ bindet Kofaktorproteine direkt in Abwesenheit von Phospholipiden. Es wird allgemein angenommen, das Kofaktor- unabhängige aPL (Typ 1) mit Infektionen assoziiert sind und – wichtiger noch – nicht pathogen sind, während pathogene aPL zum zweiten und insbesondere dritten Typ gehören. Diese Vorstellung ist speziell im Hinblick auf Typ 1 aPL nicht unumstritten und neue Forschungsergebnisse zeigen, dass sie wissenschaftlich unhaltbar ist. Wir fassen die verfügbaren Daten zur pathogenetischen Rolle der aPL zusammen und diskutieren deren Konsequenzen für die Diagnose und weitere Erforschung des APS.

Keywords

antiphospholipid syndrome - antiphospholipid antibodies - ß2-glycoprotein I - thrombosis

Schlüsselwörter

Antiphospholipidsyndrom - Antiphospholipid-Antikörper - ß2-Glykoprotein I - Thrombose

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