Antiphospholipid syndrome

Summary

The antiphospholipid syndrome (APS) is a non-inflammatory autoimmune disease characterized by the presence of antiphospholipid antibodies (aPL) in the plasma of patients with vascular thrombosis, recurrent complications of pregnancy, or both (1, 2). The presence of aPL in plasma of patients can be detected with either a prolongation of phospholipid dependent coagulation tests (lupus anticoagulant, LAC), or with solid phase immune assays against the protein β₂-glycoprotein I (β₂-GPI) or the phospholipid cardiolipin (anti-β₂-GPI antibody ELISA and anti-cardiolipin antibody ELISA, respectively) (3). For a long time there was a lot of confusion on who had the syndrome and who not. To solve this dispute, an international consensus meeting was organized in Sapporo in 1999 to formulate classification criteria for patients with the antiphospholipid syndrome (4). These criteria have been updated in 2004 at another international consensus meeting in Sydney (5). The classification criteria were defined for scientific purposes and were aimed to be used as inclusion criteria in patient related studies. They were specifically not defined for diagnostic purposes. However, current practice is that these criteria are used as a diagnostic tool. This is very unfortunate because the specificity of the different aPL assays to detect the clinical manifestations that characterize APS are disputable. One of the aims of defining the criteria was to initiate studies to determine the value of the different anti-phospholipid antibody assays to serve as biomarker for the risk of thrombosis and pregnancy morbidity. The recent progress made on this important topic will be discussed.

Zusammenfassung

Das Antiphospholipidsyndrom (APS) ist eine nicht entzündliche Autoimmunerkrankung, die durch Antiphospholipid-Antikörper (aPL) im Plasma von Patienten mit vaskulärer Thrombose, rezidivierenden Schwangerschaftskomplikationen oder beidem gekennzeichnet ist (1, 2). Das Vorhandensein von aPL im Patienten-plasma kann entweder über eine Verlänge-rung der Phospholipid-abhängigen Gerinnungstests (Lupus-Antikoagulans, LA) oder mittels Festphasen-Immunassay gegen β₂-Glykoprotein-1 (ß₂GP-1) bzw. gegen das Phospholipid Cardiolipin festgestellt werden (Anti-ß₂GP-1-ELISA bzw. Anti-Cardiolipin-ELI-SA) (3). Lange Zeit gab es erhebliche Verwirrung darüber, wer unter dem Syndrom leidet und wer nicht. Um diese Kontroverse aufzulösen, wurde 1999 in Sapporo eine internationale Konsensuskonferenz einberufen, die Klassifikationskriterien für Patienten mit APS formulieren sollte (4). Diese Kriterien wurden 2004 in einer weiteren internationalen Konsensuskonferenz in Sydney aktualisiert (5). Die Klassifikationskriterien wurden für wissenschaftliche Zwecke definiert und sollten als Einschlusskriterien für Patientenstudien dienen. Sie wurden ausdrücklich nicht für diagnostische Zwecke definiert. Jedoch werden diese Kriterien in der Praxis zur Diagnostik genutzt. Dies ist sehr unglücklich, da die Spezifi-tät der verschiedenen aPL-Assays bei der Aufdeckung der für APS charakteristischen klinischen Manifestationen strittig ist. Eines der Ziele bei der Definition der Kriterien bestand darin, Studien zu initiieren, in denen die Bedeutung der einzelnen Anti-Phospholipid-Antikörper-Assays als Biomarker für das Risiko von Thrombosen und Schwangerschaftsmor-bidität untersucht werden sollte. Der jüngst erreichte Fortschritt bei diesem wichtigen Problem wird diskutiert.

Keywords

Antiphospholipid antibodies - Lupus anticoagulant - β₂-glycoprotein I

Schlüsselwörter

Antiphospholipid-Antikörper - Lupus-Antikoagulans - β₂-Glykoprotein-1

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