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Altered β 2 ‐glycoprotein I expression on microparticles in the presence of antiphospholipid antibodies
Author(s) -
Mobarrez F.,
Gunnarsson I.,
Svenungsson E.
Publication year - 2017
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.13765
Subject(s) - antiphospholipid syndrome , antibody , medicine , immunology , flow cytometry , glycoprotein , antigen , lupus anticoagulant , systemic lupus erythematosus , biology , microbiology and biotechnology , disease
Essentials β2 glycoprotein‐I (β 2 GPI) is a scavenger molecule that binds to microparticles (MPs). β 2 GPI expression on MPs was measured in systemic lupus erythematosus (SLE) patients and controls. β 2 GPI positive MPs is depressed among SLE patients positive for antiphospholipid antibodies. Complex formation between β 2 GPI on MPs and patients own anti‐β 2 GPI may disturb MP clearance.Click to hear an ISTH Academy presentation on antiphospholipid antibody syndrome by Drs de Laat and BertolacciniSummary Background Antiphospholipid antibodies (a PL s) together with thrombosis and/or pregnancy morbidities characterize the antiphospholipid syndrome. β 2 ‐Glycoprotein I (β 2 GPI ), the most important antigen for a PL s, is a scavenger molecule that specifically binds to phosphatidylserine ( PS ) expressed on microparticles ( MP s). Objectives To evaluate β 2 GPI ‐expressing MP s in patients with systemic lupus erythematosus ( SLE ) stratified for a PL status, and in healthy controls. Patients/Methods We investigated 18 a PL /anti‐β 2 GPI ‐positive and 22 a PL ‐negative patients from a large SLE cohort and 19 healthy controls. β 2 GPI ‐positive MP s and IgG‐positive MP s were detected by flow cytometry. We measured plasma levels of β 2 GPI , and performed in vitro experiments to investigate the binding properties of β 2 GPI on MP s. Results SLE patients had more MP s and IgG‐positive MP s than controls. We observed fewer β 2 GPI ‐positive MP s in a PL /anti‐β 2 GPI ‐positive patients than in a PL /anti‐β 2 GPI ‐negative patients and controls (approximately two‐fold). β 2 GPI levels in plasma did not differ with a PL /anti‐β 2 GPI status in patients; however, controls had slightly higher levels of β 2 GPI than a PL /anti‐β 2 GPI ‐positive patients. In vitro experiments revealed that β 2 GPI preferentially binds to PS ‐positive MPs. Conclusions Despite abundant total MP s and MP s in immune complexes, β 2 GPI ‐positive MP s were depleted in SLE patients, and the levels were especially low in a PL /anti‐β 2 GPI ‐positive patients. We suggest that anti‐β 2 GPI antibodies bind to β 2 GPI – PS complexes expressed on MP s. Consequent loss of β 2 GPI – PS expression on MP s may impair scavenging and contribute to the accumulation of circulating PS ‐negative MP s, a possible source of autoantigens. Autoantibodies delaying MP clearance may thus constitute an important mechanism underlying autoimmunity.