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Review
. 2024 Dec 1;63(12):3243-3254.
doi: 10.1093/rheumatology/keae178.

Can complement activation be the missing link in antiphospholipid syndrome?

Veronica Venturelli  1   2   3 , Beatrice Maranini  1 , Ibrahim Tohidi-Esfahani  4   5 , David A Isenberg  2 , Hannah Cohen  3   6 , Maria Efthymiou  3   6
Affiliations
Review

Can complement activation be the missing link in antiphospholipid syndrome?

Veronica Venturelli et al. Rheumatology (Oxford). .

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 recognized, 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 of clinical implications and current therapeutics.

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

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Figures

Figure 1.
Figure 1.
The complement cascade. Created with BioRender.com. Ab: antibody; Ag: antigen; MAC: membrane attack complex; MAMPs: microorganism-associated molecular patterns; MBL: mannose-binding lectin; TF: tissue factor
Figure 2.
Figure 2.
Methods to measure complement activation. Created with BioRender.com. Adv: advantages; Disadv: disadvantages; mHam: modified Ham
Figure 3.
Figure 3.
Platelet activation. Created with BioRender.com. CS: chondroitin sulphate; ECM: extracellular matrix; PLT: platelet; vWF: von Willebrand Factor; PS: phosphatidylserine; GPIbα: glycoprotein Ibα
See this image and copyright information in PMC

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