Pathophysiology of Antiphospholipid Syndrome

Area of Science:

• Immunology
• Hematology
• Obstetrics

Background:

• Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by autoantibodies against phospholipid-binding proteins and phospholipids.
• These antibodies trigger cellular activation, coagulation, and complement cascades, leading to thrombotic events and pregnancy morbidity.
• Key autoantibodies target proteins like β2-glycoprotein I, prothrombin, annexins, and cardiolipin.

Purpose of the Study:

• To elucidate the mechanisms of autoantibody-mediated pathology in antiphospholipid syndrome.
• To explore novel therapeutic strategies beyond current immunomodulatory agents.

Main Methods:

• Review of existing literature on antiphospholipid syndrome pathogenesis and autoantibody targets.
• Analysis of the prothrombotic, atherogenic, and anti-fetal effects of various antiphospholipid antibodies.
• Discussion of emerging treatment modalities including vaccines and B-cell targeted therapies.

Main Results:

• Antiphospholipid antibodies, particularly lupus anticoagulants, promote thrombosis by augmenting thrombin production.
• Other antibodies contribute to atherosclerosis by increasing lipid peroxidation and impair fetal outcomes by affecting placental function.
• Current management relies on immunomodulatory agents, but significant unmet needs remain.

Conclusions:

• Antiphospholipid syndrome is driven by a diverse array of autoantibodies with multiple pathogenic mechanisms.
• Future treatments may involve targeted therapies such as autoantigen vaccines, blocking antibody production, or selective B-cell depletion.