Altered β 2 -glycoprotein I expression on microparticles in the presence of antiphospholipid antibodies.

Essentials β2 glycoprotein-I (β2 GPI) is a scavenger molecule that binds to microparticles (MPs). β2 GPI expression on MPs was measured in systemic lupus erythematosus (SLE) patients and controls. β2 GPI positive MPs is depressed among SLE patients positive for antiphospholipid antibodies. Complex formation between β2 GPI on MPs and patients own anti-β2 GPI may disturb MP clearance. Click to hear an ISTH Academy presentation on antiphospholipid antibody syndrome by Drs de Laat and Bertolaccini SUMMARY: Background Antiphospholipid antibodies (aPLs) together with thrombosis and/or pregnancy morbidities characterize the antiphospholipid syndrome. β2 -Glycoprotein I (β2 GPI), the most important antigen for aPLs, is a scavenger molecule that specifically binds to phosphatidylserine (PS) expressed on microparticles (MPs). Objectives To evaluate β2 GPI-expressing MPs in patients with systemic lupus erythematosus (SLE) stratified for aPL status, and in healthy controls. Patients/Methods We investigated 18 aPL/anti-β2 GPI-positive and 22 aPL-negative patients from a large SLE cohort and 19 healthy controls. β2 GPI-positive MPs and IgG-positive MPs were detected by flow cytometry. We measured plasma levels of β2 GPI, and performed in vitro experiments to investigate the binding properties of β2 GPI on MPs. Results SLE patients had more MPs and IgG-positive MPs than controls. We observed fewer β2 GPI-positive MPs in aPL/anti-β2 GPI-positive patients than in aPL/anti-β2 GPI-negative patients and controls (approximately two-fold). β2 GPI levels in plasma did not differ with aPL/anti-β2 GPI status in patients; however, controls had slightly higher levels of β2 GPI than aPL/anti-β2 GPI-positive patients. In vitro experiments revealed that β2 GPI preferentially binds to PS-positive MPs. Conclusions Despite abundant total MPs and MPs in immune complexes, β2 GPI-positive MPs were depleted in SLE patients, and the levels were especially low in aPL/anti-β2 GPI-positive patients. We suggest that anti-β2 GPI antibodies bind to β2 GPI-PS complexes expressed on MPs. Consequent loss of β2 GPI-PS expression on MPs may impair scavenging and contribute to the accumulation of circulating PS-negative MPs, a possible source of autoantigens. Autoantibodies delaying MP clearance may thus constitute an important mechanism underlying autoimmunity.