Large-scale analysis of tumor necrosis factor α levels in systemic lupus erythematosus

Corinna E. Weckerle, Dorothy Mangale, Beverly S. Franek, Jennifer A. Kelly, Marissa Kumabe, Judith A. James, Kathy L. Moser, John B. Harley, Timothy B. Niewold

Research output: Contribution to journalArticle

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Abstract

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 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. Methods 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. Results 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. Conclusion 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.

Original languageEnglish (US)
Pages (from-to)2947-2952
Number of pages6
JournalArthritis and Rheumatism
Volume64
Issue number9
DOIs
StatePublished - Sep 2012
Externally publishedYes

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Systemic Lupus Erythematosus
Tumor Necrosis Factor-alpha
Serum
Interferons
African Americans
Autoantibodies
Hispanic Americans
Meta-Analysis
Multivariate Analysis
Enzyme-Linked Immunosorbent Assay
Odds Ratio
Cytokines

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Weckerle, C. E., Mangale, D., Franek, B. S., Kelly, J. A., Kumabe, M., James, J. A., ... Niewold, T. B. (2012). Large-scale analysis of tumor necrosis factor α levels in systemic lupus erythematosus. Arthritis and Rheumatism, 64(9), 2947-2952. https://doi.org/10.1002/art.34483

Large-scale analysis of tumor necrosis factor α levels in systemic lupus erythematosus. / Weckerle, Corinna E.; Mangale, Dorothy; Franek, Beverly S.; Kelly, Jennifer A.; Kumabe, Marissa; James, Judith A.; Moser, Kathy L.; Harley, John B.; Niewold, Timothy B.

In: Arthritis and Rheumatism, Vol. 64, No. 9, 09.2012, p. 2947-2952.

Research output: Contribution to journalArticle

Weckerle, CE, Mangale, D, Franek, BS, Kelly, JA, Kumabe, M, James, JA, Moser, KL, Harley, JB & Niewold, TB 2012, 'Large-scale analysis of tumor necrosis factor α levels in systemic lupus erythematosus', Arthritis and Rheumatism, vol. 64, no. 9, pp. 2947-2952. https://doi.org/10.1002/art.34483
Weckerle CE, Mangale D, Franek BS, Kelly JA, Kumabe M, James JA et al. Large-scale analysis of tumor necrosis factor α levels in systemic lupus erythematosus. Arthritis and Rheumatism. 2012 Sep;64(9):2947-2952. https://doi.org/10.1002/art.34483
Weckerle, Corinna E. ; Mangale, Dorothy ; Franek, Beverly S. ; Kelly, Jennifer A. ; Kumabe, Marissa ; James, Judith A. ; Moser, Kathy L. ; Harley, John B. ; Niewold, Timothy B. / Large-scale analysis of tumor necrosis factor α levels in systemic lupus erythematosus. In: Arthritis and Rheumatism. 2012 ; Vol. 64, No. 9. pp. 2947-2952.
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abstract = "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 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. Methods 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. Results 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. Conclusion 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.",
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N2 - 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 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. Methods 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. Results 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. Conclusion 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.

AB - 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 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. Methods 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. Results 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. Conclusion 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.

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