Complement in the Pathophysiology of the Antiphospholipid Syndrome

Area of Science:

• Immunology
• Hematology
• Rheumatology

Background:

• Antiphospholipid syndrome (APS) is defined by thrombosis and pregnancy complications linked to antiphospholipid antibodies (aPL).
• The complement system, part of innate immunity, interacts with coagulation and may drive APS pathogenesis.
• Growing evidence suggests complement activation by aPL contributes to clinical manifestations of APS.

Purpose of the Study:

• To explore the role of complement activation in antiphospholipid syndrome.
• To investigate the mechanisms by which complement contributes to aPL-associated thrombosis and pregnancy morbidity.
• To assess the therapeutic potential of complement inhibition in APS.

Main Methods:

• Review of existing literature on complement activation in APS.
• Analysis of experimental data from animal models (mice) with complement deficiencies or inhibitors.
• Examination of clinical data on complement activation products in APS patients.

Main Results:

• Complement activation by aPL generates C5a, promoting procoagulant activity.
• aPL-induced fetal loss and thrombosis in mice are attenuated in complement-deficient models.
• Increased complement activation products are found in APS patients, but clinical correlation needs further study.
• Eculizumab has shown success in treating catastrophic APS and related complications.

Conclusions:

• Complement activation is implicated in the pathogenesis of antiphospholipid syndrome.
• Complement inhibition is a promising therapeutic strategy for APS, particularly severe forms.
• Further research is needed to fully elucidate complement's role and optimize therapeutic targeting in APS.