Familial Aggregation of High Tumor Necrosis Factor Alpha Levels in Systemic Lupus Erythematosus

• Published in: Clinical & developmental immunology Vol. 2013; no. 2013; pp. 1 - 6
• Main Authors: Niewold, Timothy B., Sivils, Kathy L., Harley, John B., Kelly, Jennifer A., Kumabe, Marissa, Chrabot, Beverly S., Kariuki, Silvia N., Mangale, Dorothy, James, Judith A.
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2013; Hindawi Limited
• Subjects: Adult; Autoimmune diseases; Case-Control Studies; Data processing; Disease; Environment; Family; Female; Genomics; Hospitals; Humans; Immunology; Interferon-alpha - blood; Interferon-alpha - metabolism; Lupus; Lupus Erythematosus, Systemic - metabolism; Male; Middle Aged; Pathogenesis; Rheumatology; Tumor Necrosis Factor-alpha - blood; Tumor Necrosis Factor-alpha - metabolism; Young Adult
• ISSN: 2314-8861; 1740-2522; 2314-7156; 1740-2530
• DOI: 10.1155/2013/267430

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.