Familial aggregation of high tumor necrosis factor alpha levels in systemic lupus erythematosus

Dorothy Mangale, Silvia N. Kariuki, Beverly S. Chrabot, Marissa Kumabe, Jennifer A. Kelly, John B. Harley, Judith A. James, Kathy L. Sivils, Timothy B. Niewold

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Abstract

Systemic lupus erythematosus (SLE) patients frequently have high circulating tumor necrosis factor alpha (TNF-α) levels. We explored circulating TNF-α levels in SLE families to determine whether high levels of TNF-α were clustered in a heritable pattern. We measured TNF-α in 242 SLE patients, 361 unaffected family members, 23 unaffected spouses of SLE patients, and 62 unrelated healthy controls. Familial correlations and relative recurrence risk rates for the high TNF-α trait were assessed. SLE-affected individuals had the highest TNF-α levels, and TNF-α was significantly higher in unaffected first degree relatives than healthy unrelated subjects (P = 0.0025). No Mendelian patterns were observed, but 28.4% of unaffected first degree relatives of SLE patients had high TNF-α levels, resulting in a first degree relative recurrence risk of 4.48 (P = 2.9 × 10 - 5). Interestingly, the median TNF-α value in spouses was similar to that of the first degree relatives. Concordance of the TNF-α trait (high versus low) in SLE patients and their spouses was strikingly high at 78.2%. These data support a role for TNF-α in SLE pathogenesis, and TNF-α levels may relate with heritable factors. The high degree of concordance in SLE patients and their spouses suggests that environmental factors may also play a role in the observed familial aggregation.

Original languageEnglish (US)
Article number267430
JournalClinical and Developmental Immunology
Volume2013
DOIs
StatePublished - Oct 21 2013

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Mangale, D., Kariuki, S. N., Chrabot, B. S., Kumabe, M., Kelly, J. A., Harley, J. B., James, J. A., Sivils, K. L., & Niewold, T. B. (2013). Familial aggregation of high tumor necrosis factor alpha levels in systemic lupus erythematosus. Clinical and Developmental Immunology, 2013, [267430]. https://doi.org/10.1155/2013/267430