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


CONCLUSIONS
The HLA class II and PBMC proliferation data suggest that beta2GPI may be both a T- and B-cell autoantigen in SLE.
Davies
M L
ML
Rheumatology Department, Division of Immunity and Infection, University of Birmingham Medical School, Birmingham, UK.
Young
S P
SP
Welsh
K
K
Bunce
M
M
Wordsworth
B P
BP
Davies
K A
KA
Wagenknecht
D R
DR
Taylor
E
E
Gordon
C
C
Jobson
S
S
Briggs
D
D
Bowman
S J
SJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016736:Antiphospholipid Syndrome / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D006681:HLA-D Antigens / Q000032:analysis / Q000145:classification; D006650:Histocompatibility Testing; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D053482:beta 2-Glycoprotein I
D006023:Glycoproteins; D006681:HLA-D Antigens; D053482:beta 2-Glycoprotein I; D004247:DNA