Newly understood mechanisms in the chemistry of inflammation at the glycoprotein targeted by antibodies in antiphospholipid syndrome suggest therapeutic targets
Last week's articles on rheumatology in the major nonspecialty journalsAntiphospholipid syndromeThe pathogenesis of the antiphospholipid syndromeN Engl J Med, Mar. 14, 2013. Full text $15
Oxidation unmasks a critical antiphospholipid syndrome (APS) antigenic site. β2-glycoprotein I (β2GPI) is a target protein of antibodies that are diagnostic of APS. β2GPI has its head in the blood circulation, setting off an immune attack, and its feet in the vascular epithelium, setting off a coagulation cascade. This review by two authors from the Department of Medicine at the University of New South Wales in Sydney, Australia, describes how, under oxidative stress, disulfide bonds form at sites on the glycoprotein molecule and provoke inflammation in patients with APS. One of these binds to a B cell epitope, and also to complement. Another binds to a vascular endothelium receptor, and initiates a coagulation cascade. As 40% of APL patients also have lupus, and lupus antibodies react similarly, there may be an "overlap in pathogenesis" of the two conditions.