Large-Scale Analysis of Tumor Necrosis Factor α Levels in Systemic Lupus Erythematosus

Objective. Systemic lupus erythematosus (SLE) disease manifestations are highly variable among patients, and the prevalence of individual clinical features differs significantly by ancestry. Serum tumor necrosis factor alpha (TNF alpha) levels are elevated in some SLE patients and may play a role in disease pathogenesis. The aim of this study was to look for associations between serum TNF alpha levels, clinical manifestations of SLE, autoantibodies, and serum interferon-alpha (IFN alpha) levels in a large multiancestral SLE cohort. Methods. We studied serum TNF alpha levels in 653 SLE patients (214 African Americans, 298 European Americans, and 141 Hispanic Americans). TNF alpha was measured using an enzyme-linked immunosorbent assay, and IFN alpha was measured with a functional reporter cell assay. Stratified and multivariate analyses were used to detect associations in each ancestral background separately, with meta-analysis when appropriate. Results. Serum TNF alpha levels were significantly higher in SLE patients than in non-autoimmune disease controls (P < 5.0 x 10(-3) for each ancestral background). High serum TNF alpha levels were positively correlated with high serum IFN alpha levels when tested in the same sample across all ancestral backgrounds (odds ratio range 1.76-1.86, P = 4.8 x 10(-3) by Fisher's combined probability test). While serum TNF alpha levels alone did not differ significantly among SLE patients of different ancestral backgrounds, the proportion of patients with concurrently high levels of TNF alpha and IFN alpha was highest in African Americans and lowest in European Americans (P = 5.0 x 10(-3)). Serum TNF alpha levels were not associated with autoantibodies, clinical criteria for the diagnosis of SLE, or age at the time of sampling. Conclusion. Serum TNF alpha levels are high in many SLE patients, and we observed a positive correlation between serum TNF alpha and IFN alpha levels. These data support a role for TNF alpha in the pathogenesis of SLE across all ancestral backgrounds and suggest important cytokine subgroups within the disease.