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Clinical correlates, serum autoantibodies and the role of the major histocompatibility complex in French Canadian and non-French Canadian Caucasians with SLE

D M Boisert

R Goldstein

Division of Rheumatology, Department of Medicine, Ottawa General Hospital, University of Ottawa

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, Cl = 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, Cl = 1.4, 16.2) and anti-La (P = 0.02, RR = 11.7, Cl = 1.4, 549) autoantibodies. This relationship was also significant for anti-Ro antibody in the French Canadian patients (P = 0.01, RR = 21.3, Cl = 1.7, 105.3). In contrast, anti-dsDNA autoantibodies were negatively associated with photosensitivity (P = 0.02, RR = 0.3, Cl = 0.07, 0.8) and correlated with HLA-DR15 (P = 0.006, RR = 4.2, Cl = 1.5, 12.8) and Dw2 (P = 0.009, RR = 3.9, Cl = 1.4, 11.9).

Conclusion: 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.

Key Words: major histocompatibilty complex • systemic lupus erythematosus • autoantibody

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