Tracing the molecular pathogenesis of antiphospholipid syndrome.
Fetal loss induced by antiphospholipid antibodies (aPLs) in mice is a complement-driven inflammatory condition. Engagement of the complement receptor C5aR on neutrophils induces expression of the principal initiator of the blood clotting mechanism, tissue factor (TF), and blocking this downstream event of complement activation prevents antibody-induced fetal loss. In this issue of the JCI, the study by Redecha et al. clarifies that in mice, the contribution of TF to this pathogenic mechanism is independent of its role in coagulation and thrombosis, but involves inflammatory signaling through the receptor PAR2 (see the related article beginning on page 3453). The study not only sheds light on a critical effector mechanism of aPL-induced fetal loss, but also suggests that treatment with statins, which decrease TF and PAR2 expression, may hold promise as a therapeutic approach to antiphospholipid syndrome-associated pregnancy complications.
Weiler
Hartmut
H
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, Wisconsin, USA.
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D005313:Fetal Death / Q000503:physiopathology; D006801:Humans; D051379:Mice; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D044464:Receptor, PAR-2 / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000276:immunology
D017152:Antibodies, Antiphospholipid; D044464:Receptor, PAR-2; D013925:Thromboplastin