科研之友
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摘要
Background Antiphospholipid antibodies (aPLs) together with thrombosis and/or pregnancy morbiditiescharacterize the antiphospholipid syndrome. (2)-GlycoproteinI ((2)GPI), the most important antigen for aPLs, is a scavenger molecule that specifically binds to phosphatidylserine (PS) expressed on microparticles (MPs). Objectives To evaluate (2)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-(2)GPI-positive and 22 aPL-negative patients from a large SLE cohort and 19 healthy controls. (2)GPI-positive MPs and IgG-positive MPs were detected by flow cytometry. We measured plasma levels of (2)GPI, and performed invitro experiments to investigate the binding properties of (2)GPI on MPs. Results SLE patients had more MPs and IgG-positive MPs than controls. We observed fewer (2)GPI-positive MPs in aPL/anti-(2)GPI-positive patients than in aPL/anti-(2)GPI-negative patients and controls (approximately two-fold). (2)GPI levels in plasma did not differ with aPL/anti-(2)GPI status in patients; however, controls had slightly higher levels of (2)GPI than aPL/anti-(2)GPI-positive patients. Invitro experiments revealed that (2)GPI preferentially binds to PS-positive MPs. Conclusions Despite abundant total MPs and MPs in immune complexes, (2)GPI-positive MPs were depleted in SLE patients, and the levels were especially low in aPL/anti-(2)GPI-positive patients. We suggest that anti-(2)GPI antibodies bind to (2)GPI-PS complexes expressed on MPs. Consequent loss of (2)GPI-PS expression on MPs may impair scavenging and contribute to the accumulation ofcirculating PS-negative MPs, a possible source of autoantigens. Autoantibodies delaying MP clearance may thus constitute an important mechanism underlying autoimmunity.
- 出版日期2017-9
