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Heterogeneity of antibodies to ß2-glycoprotein 1 from patients with systemic lupus erythematosus

Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico, acabral{at}quetzal.innsz.mx

J Cabiedes

Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

D Alarcón-Segovia

Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico

We studied antibodies to ß₂-glycoprotein 1 (anti-ß₂ GP1) from 72 patients with systemic lupus erythematosus (SLE) with or without antiphospholipid syndrome (APS) or with or without anticardiolipin antibodies (aCL). Fifteen patients had APS and positive antiphospholipid antibodies [clinical APS()/aPL()], 12 patients had APS, negative serum IgG and IgM aCL, anti-phosphatidylethanolamine, anti-phosphatidylserine and no lupus anticoagulant [clinical APS()/aPL(-)]. A third group included 16 patients without APS but high aCL levels [clinical APS(-)/aPL()]. In a fourth group we studied 29 patients without clinical manifestations of APS or aCL [clinical APS(-)/aPL(-)]. One hundred anticardiolipin and VDRL-negative normal sera were studied as controls. IgG antibodies to cardiolipin proper in a bovine ß₂ GP-free system, to human b2GP1 immobilized on cardiolipinor to human ß₂ GP1 alone were detected in all sera by ELISA using irradiated and nonirradiated plates from two manufacturers. Sera from APS()/aPL() patients showed IgG binding to CL, CL ß₂ GP1 and ß₂ GP1 in irradiated and nonirradiatedplates. APS()/aPL(-) sera had more significant IgG binding to ß₂ GP1 than normal controls when studied in both irradiated or nonirradiatedplates (P 0.001). This binding was inhibited by solid-phase cardiolipin in a dose-dependentmanner. Sera from the APS(-)/aPL() subgroup had comparable IgG activity in both the CL and CL ß₂ GP1 assays, while no anti-ß₂ GP1 activity was detected in these sera. Sera from the clinical APS(-)/aPL(-) patients were negative in the three ELISA systems. Antibodies to human ß₂ GP1 from SLE patients recognize various epitopes. Those from APS()/aPL() patients appear to react with an epitope boosted by cardiolipin in addition to another one present in the native protein. In contrast, anti-ß₂ GP1 from patients with APS()/aPL(-) are blocked by cardiolipin, suggestingthat their epitope is the phospholipid-binding site.

Key Words: antibodies to human ß2-glycoprotein 1 • antiphospholipid antibodies • antiphospholipid syndrome • systemic lupus erythematosus

Lupus, Vol. 13, No. 3, 182-187 (2004)
DOI: 10.1191/0961203303lu531oa


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