Can complement activation be the missing link in antiphospholipid syndrome?

Rheumatology (Oxford). 2024 Mar 14:keae178. doi: 10.1093/rheumatology/keae178. Online ahead of print.

Abstract

APS is an autoimmune disorder with life-threatening complications that, despite therapeutic advantages, remains associated with thrombotic recurrences and treatment failure. The role of complement activation in APS pathogenesis is increasingly recognised, specifically in obstetric APS. However, its exact role in thrombotic APS and on the severity of the disease is not yet fully elucidated. Further mechanistic studies are needed to delineate the role of complement activation in the various APS clinical manifestations with aim to identify novel markers of disease severity, together with clinical trials to evaluate the efficacy of complement inhibition in APS. This could ultimately improve risk stratification in APS, patient tailored targeted therapy with complement inhibition identified as an adjunctive treatment. This article reviews current findings and challenges about complement activation in APS, discusses the potential role of platelet mediated complement activation in this setting and provides an overview on clinical implications and current therapeutics.

Keywords: antiphospholipid antibodies; antiphospholipid syndrome; coagulation; complement; pregnancy outcomes; thrombosis.