Immune responses to native beta(2)-glycoprotein I in patients with systemic lupus erythematosus and the antiphospholipid syndrome

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 vit...

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Bibliographic Details
Published in:	Rheumatology (Oxford, England) England), 2002-04, Vol.41 (4), p.395-400
Main Authors:	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, Bowman, S J
Format:	Article
Language:	eng
Subjects:	Adolescent Adult Aged Aged, 80 and over Antiphospholipid Syndrome - genetics Antiphospholipid Syndrome - immunology beta 2-Glycoprotein I Cells, Cultured DNA - analysis Dose-Response Relationship, Immunologic Enzyme-Linked Immunosorbent Assay Female Glycoproteins - genetics Glycoproteins - immunology Histocompatibility Testing HLA-D Antigens - analysis HLA-D Antigens - classification Humans Lupus Erythematosus, Systemic - genetics Lupus Erythematosus, Systemic - immunology Lymphocyte Activation Male Middle Aged Monocytes - cytology Monocytes - immunology Polymerase Chain Reaction T-Lymphocytes - immunology
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Summary:	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. 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. 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-DRB10401/4/8, DR11 or DRB11302 (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). The HLA class II and PBMC proliferation data suggest that beta2GPI may be both a T- and B-cell autoantigen in SLE.
ISSN:	1462-0324 1462-0332