title: Familial aggregation of high tumor necrosis factor alpha levels in systemic lupus erythematosus.
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.
authors.affiliation: Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Mangale
authors.forename: Silvia N
authors.initials: SN
authors.lastname: Kariuki
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Chrabot
authors.forename: Marissa
authors.initials: M
authors.lastname: Kumabe
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Kelly
authors.forename: John B
authors.initials: JB
authors.lastname: Harley
authors.forename: Judith A
authors.initials: JA
authors.lastname: James
authors.forename: Kathy L
authors.initials: KL
authors.lastname: Sivils
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Niewold
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004777:Environment; D005190:Family; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000097:blood / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha