Immune responses to native beta2-glycoprotein I in patients with systemic lupus erythematosus and the antiphospholipid syndrome

Davies, M.L., Young, S.P., Welsh, K., Bunce, M., Wordsworth, B.P., Davies, K.A., Wagenknecht, D.R., Taylor, E., Gordon, C., Jobson, S., Briggs, D. and Bowman, S.J. (2002) Immune responses to native beta2-glycoprotein I in patients with systemic lupus erythematosus and the antiphospholipid syndrome. Rheumatology, 41 (4). pp. 395-400.

Abstract

Objective. To identify HLA class II associations with anti β2-glycoprotein I (β2GPI) 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 β2GPI in vitro.

Methods. Anti-β2GPI 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 β2GPI 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-β2GPI 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-β2GPI antibodies had greater median stimulation indices to β2GPI in vitro compared with the 15 controls studied (P = 0.04).

Conclusion. The HLA class II and PBMC proliferation data suggest that β2GPI may be both a T- and B-cell autoantigen in SLE.