A genetic association between systemic lupus erythematosus and tumor necrosis factor alpha

We have investigated the significance of tumor necrosis factor alpha (TNF‐α) polymorphism in relation to systemic lupus erythematosus (SLE) and autoantibody production. Typing of HLA‐B, ‐DR and TNF was performed in 81 Caucasian SLE patients and 168 Caucasian controls. The presence of anti‐Ro and anti‐La antibodies was also determined in patients. The frequency of the TNF2 allele increased in SLE compared with controls [0.24 vs. 0.17, p = 0.04, odds ratio (OR) = 1.6], as did HLA‐DR3 (0.25 vs. 0.13, p < 0.01, OR = 2.3) and HLA‐B8 (0.23 vs. 0.15, p = 0.02, OR = 2). Although HLA‐DR3 showed the strongest disease association, we could not demonstrate association of HLA‐DR3 or TNF2 with SLE independently of each other. Within SLE a much stronger association of TNF2 was seen with autoantibody production: anti‐Ro antibody (0.39 vs. 0.16, p < 0.001, OR = 3.4) and anti‐La antibody (0.43 vs. 0.19, p < 0.001, OR = 3.2). When analyzed independently of each other, however, HLA‐DR3 remained significantly associated with autoantibodies, while TNF2 did not. These data suggest that on the B8‐DR3 haplotype, TNF‐α polymorphism may play a role in SLE susceptibility, but it is not primarily associated with autoantibody production.