Systemic Lupus Erythematosus
Brief Report: Large-scale analysis of tumor necrosis factor α levels in systemic lupus erythematosus
Article first published online: 27 AUG 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 9, pages 2947–2952, September 2012
How to Cite
Weckerle, C. E., Mangale, D., Franek, B. S., Kelly, J. A., Kumabe, M., James, J. A., Moser, K. L., Harley, J. B. and Niewold, T. B. (2012), Brief Report: Large-scale analysis of tumor necrosis factor α levels in systemic lupus erythematosus. Arthritis & Rheumatism, 64: 2947–2952. doi: 10.1002/art.34483
- Issue published online: 27 AUG 2012
- Article first published online: 27 AUG 2012
- Accepted manuscript online: 5 APR 2012 11:46AM EST
- Manuscript Accepted: 22 MAR 2012
- Manuscript Received: 9 AUG 2011
- American College of Rheumatology Research and Education Foundation Rheumatology Scientist Development award
- Lupus Family Registry and Repository
- NIH. Grant Numbers: AR-62277, AR-42460, AI-24717, RR-015577, RR-031152, AR-048940, AR-045084, AR-053483, AR-058554, AI-082714, AR-62277, AR-42460, AI-53747, AI-31584, DE-15223, RR-20143, AI-24717, AI-62629, AR-48940, AI-83194, AR-49084
- Mary Kirkland Scholar
- Lou Kerr Chair in Biomedical Research
- Department of Veterans Affairs
- Alliance for Lupus Research, and Rheuminations, Inc.
- Lupus Research Institute
- Arthritis National Research Foundation
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 α (TNFα) 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 TNFα levels, clinical manifestations of SLE, autoantibodies, and serum interferon-α (IFNα) levels in a large multiancestral SLE cohort.
We studied serum TNFα levels in 653 SLE patients (214 African Americans, 298 European Americans, and 141 Hispanic Americans). TNFα was measured using an enzyme-linked immunosorbent assay, and IFNα 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.
Serum TNFα levels were significantly higher in SLE patients than in non–autoimmune disease controls (P < 5.0 × 10−3 for each ancestral background). High serum TNFα levels were positively correlated with high serum IFNα levels when tested in the same sample across all ancestral backgrounds (odds ratio range 1.76–1.86, P = 4.8 × 10−3 by Fisher's combined probability test). While serum TNFα levels alone did not differ significantly among SLE patients of different ancestral backgrounds, the proportion of patients with concurrently high levels of TNFα and IFNα was highest in African Americans and lowest in European Americans (P = 5.0 × 10−3). Serum TNFα levels were not associated with autoantibodies, clinical criteria for the diagnosis of SLE, or age at the time of sampling.
Serum TNFα levels are high in many SLE patients, and we observed a positive correlation between serum TNFα and IFNα levels. These data support a role for TNFα in the pathogenesis of SLE across all ancestral backgrounds and suggest important cytokine subgroups within the disease.