title: High serum IFN-alpha activity is a heritable risk factor for systemic lupus erythematosus.
abstract: Interferon alpha (IFN-alpha) levels are elevated in many patients with systemic lupus erythematosus (SLE); however it is not known whether high serum IFN-alpha activity is a cause or a result of the disease. We studied 266 SLE patients and 405 of their healthy relatives, and frequently found high serum IFN-alpha activity in both patients and healthy relatives as compared to healthy unrelated individuals. High IFN-alpha activity was clustered in specific families in both SLE patients and their healthy first-degree relatives, suggesting a heritable trait. Heritability was also supported by quantitative familial correlation of IFN-alpha activity, concordance in affected sib pairs and frequent transmission of the high IFN-alpha activity trait from parents to offspring. Autoantibodies to RNA-binding proteins and double-stranded DNA were associated with high IFN-alpha activity in SLE patients; however these autoantibodies were very uncommon in healthy family members and did not explain the observed familial correlations. The frequency of high IFN-alpha activity was similar across all studied ethnic backgrounds. These data suggest that high serum IFN-alpha activity is a complex heritable trait, which plays a primary role in SLE pathogenesis.
authors.affiliation: Mary Kirkland Center for Lupus Research, Hospital for Special Surgery, New York, NY, USA. niewoldt@hss.edu
authors.forename: T B
authors.initials: TB
authors.lastname: Niewold
authors.forename: J
authors.initials: J
authors.lastname: Hua
authors.forename: T J A
authors.initials: TJ
authors.lastname: Lehman
authors.forename: J B
authors.initials: JB
authors.lastname: Harley
authors.forename: M K
authors.initials: MK
authors.lastname: Crow
mesh_terms: D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D016022:Case-Control Studies; D002460:Cell Line; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D008297:Male; D016601:RNA-Binding Proteins / Q000276:immunology; D012307:Risk Factors
chemical_list: D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D016898:Interferon-alpha; D016601:RNA-Binding Proteins