Clinical correlates, serum autoantibodies and the role of the major histocompatibility complex in French Canadian and non-French Canadian Caucasians with SLE.
OBJECTIVE
To investigate the predisposing role of major histocompatibility complex (MHC) genes to autoantibody production and clinical manifestations comparing French Canadian and Non-French Canadian Caucasians with systemic lupus erythematosus (SLE) METHODS: Ninety-one Caucasian patients with SLE were studied. Clinical manifestations, autoantibody expression and HLA-A, B, (serology), DR, DQ and C4A gene deletion (restriction fragment length polymorphism [RFLP] typing) were determined.


RESULTS
Photosensitivity was present in all SLE subjects with anti-Ro antibodies (P=0.001, RR=13.1, CI=1.8, 564). Photosensitivity was further associated with the HLA-A1, C4A gene deletion haplotype. More strikingly, C4A gene deletion was associated with anti-Ro (P=0.008, RR=4.6, CI=1.4, 16.2) and anti-La (P=0.02, RR=11.7, CI=1.4, 549) autoantibodies. This relationship was also significant for anti-Ro antibody in the French Canadian patients (P=0.01, RR=21.3, CI=1.7, 105.3). In contrast, anti-dsDNA autoantibodies were negatively associated with photosensitivity (P=0.02, RR=0.3, CI=0.07, 0.8) and correlated with HLA-DR15 (P=0.006, RR=4.2, CI=1.5, 12.8) and Dw2 (P=0.009, RR=3.9, CI=1.4, 11.9).


CONCLUSIONS
C4A gene deletion has a previously unrecognized powerful association with anti-Ro and anti-La autoantibodies. These results support the concept of divergent MHC gene associations with autoantibody expression and emphasize the influence of ethnicity on the immunogenetic study of SLE.
Podrebarac
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TA
Department of Medicine, Ottawa General Hospital, University of Ottawa, Ontario, Canada. tpodrebarac@rics.bwh.harvard.edu
Boisert
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Goldstein
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D000328:Adult; D000483:Alleles; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D002170:Canada / Q000453:epidemiology; D003627:Data Interpretation, Statistical; D005260:Female; D005602:France / Q000208:ethnology; D006680:HLA Antigens / Q000235:genetics / Q000502:physiology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics* / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000235:genetics* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D044465:White People / Q000235:genetics*
D001323:Autoantibodies; D006680:HLA Antigens