Rheumatology 2002; 41: 395-400
© 2002 British Society for Rheumatology
Original Papers |
Immune responses to native ß2-glycoprotein I in patients with systemic lupus erythematosus and the antiphospholipid syndrome
Rheumatology Department, Division of Immunity and Infection, University of Birmingham Medical School, Birmingham,
1 Oxford Tissue Typing Unit, Churchill Hospital, Oxford,
2 Wellcome Trust Genetics Centre, Churchill Hospital, Oxford,
3 Imperial College School of Medicine, London, UK,
4 St Francis Hospital, Indianapolis, USA and
5 Histocompatibility and Immunogenetics Laboratory, National Blood Service, Birmingham, UK
Objective. To identify HLA class II associations with anti ß2-glycoprotein I (ß2GPI) antibodies in a cohort of Caucasian patients with systemic lupus erythematosus (SLE) and to determine whether these HLA genotypes act as restriction elements for lymphocyte proliferation to native human ß2GPI in vitro.
Methods. Anti-ß2GPI antibodies were detected in patient sera using enzyme-linked immunosorbent assays (ELISAs). HLA class II alleles (DRB1, DQB1) were determined by polymerase chain reaction-based DNA genotyping. In vitro peripheral blood mononuclear cell (PBMC) responses to native human ß2GPI were measured in a 7-day proliferation assay.
Results. We identified three groups of Caucasian SLE patients using these ELISAs. In group 1, 16 out of 18 SLE patients (89%) with anti-ß2GPI antibodies were positive for HLA-DRB1*0401/4/8, DR11 or DRB1*1302 (P=0.001 vs controls) compared with 23 out of 53 patients (43%) in group 2 with anti-cardiolipin antibodies only, 57 out of 151 patients (38%) in group 3 (SLE patients without anticardiolipin antibodies) and 109 out of 225 controls (48%). Fourteen patients with anti-ß2GPI antibodies had greater median stimulation indices to ß2GPI in vitro compared with the 15 controls studied (P=0.04).
Conclusion. The HLA class II and PBMC proliferation data suggest that ß2GPI may be both a T- and B-cell autoantigen in SLE.
KEY WORDS: SLE, ß2GPI, APS, HLA, T cell.
Correspondence to: S. J. Bowman, Rheumatology Department, Division of Immunity and Infection, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.