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

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  • F S di Giovine
  • N de Vries
  • L B van de Putte
  • G W Duff

Colleges, School and Institutes


We have investigated the significance of tumor necrosis factor alpha (TNF-alpha) 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-alpha polymorphism may play a role in SLE susceptibility, but it is not primarily associated with autoantibody production.


Original languageEnglish
Pages (from-to)191-5
Number of pages5
JournalEuropean Journal of Immunology
Issue number1
Publication statusPublished - Jan 1994


  • Autoantibodies, Base Sequence, Female, HLA-B8 Antigen, HLA-DR3 Antigen, Haplotypes, Humans, Lupus Erythematosus, Systemic, Male, Molecular Sequence Data, Tumor Necrosis Factor-alpha