Pathophysiology of thrombosis and pregnancy morbidity in the antiphospholipid syndrome.
In patients with the antiphospholipid syndrome (APS), the presence of a group of pathogenic autoantibodies called antiphospholipid antibodies causes arteriovenous thrombosis and pregnancy complications. To date, the pathogenicity of the antiphospholipid antibodies has been the focus of analysis. Recently, the antibodies were reported to be capable of direct cell activation, and research on the underlying mechanism is ongoing. The antiphospholipid antibodies bind to the membranes of vascular endothelial cells, monocytes and platelets, provoking tissue factor expression and platelet aggregation. This activation functions as intracellular signalling, independent of the cell type, to activate p38MAPK and the transcription factor NFκB. Currently, there are multiple candidates for the membrane receptors of the antiphospholipid antibodies that are being tested for potential in specific therapy. Recently, APS was reported to have significant comorbidity with complement activation, and it was proposed that this results in placental damage and cell activation and, therefore, could be the primary factor for the onset of pregnancy complications and thrombosis. The detailed mechanism of complement activation remains unknown; however, an inflammation-inducing substance called anaphylatoxin, which appears during the activation process of the classical complement pathway, is thought to be a key molecule. Complement activation occurs in tandem, regardless of the pathology of APS or the type of antiphospholipid antibody, and it is thought that this completely new understanding of the mechanism will contribute greatly to comprehension of the pathology of APS.
Department of Internal Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Kenji
K
Oku
Olga
O
Amengual
Tatsuya
T
Atsumi
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000378:metabolism; D016736:Antiphospholipid Syndrome / Q000150:complications* / Q000276:immunology; D002450:Cell Communication / Q000502:physiology; D003167:Complement Activation / Q000502:physiology; D005260:Female; D006801:Humans; D051379:Mice; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000209:etiology*; D011256:Pregnancy Outcome; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013927:Thrombosis / Q000209:etiology*
D017152:Antibodies, Antiphospholipid; D011956:Receptors, Cell Surface