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OBJECTIVE: To identify HLA class II associations with anti beta(2)-glycoprotein I (beta2GPI) 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 beta2GPI in vitro. METHODS: Anti-beta2GPI 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 beta2GPI 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-beta2GPI 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-beta2GPI antibodies had greater median stimulation indices to beta2GPI in vitro compared with the 15 controls studied (P=0.04). CONCLUSION: The HLA class II and PBMC proliferation data suggest that beta2GPI may be both a T- and B-cell autoantigen in SLE.

Original publication

DOI

10.1093/rheumatology/41.4.395

Type

Journal article

Journal

Rheumatology (Oxford, England)

Publication Date

04/2002

Volume

41

Pages

395 - 400

Addresses

Rheumatology Department, Division of Immunity and Infection, University of Birmingham Medical School, Birmingham, UK.

Keywords

T-Lymphocytes, Monocytes, Cells, Cultured, Humans, Lupus Erythematosus, Systemic, Antiphospholipid Syndrome, Glycoproteins, DNA, HLA-D Antigens, Histocompatibility Testing, Enzyme-Linked Immunosorbent Assay, Polymerase Chain Reaction, Lymphocyte Activation, Dose-Response Relationship, Immunologic, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, beta 2-Glycoprotein I