High serum IFN-alpha activity is a heritable risk factor for systemic lupus erythematosus

• Published in: Genes and immunity Vol. 8; no. 6; pp. 492 - 502
• Main Authors: Niewold, T B, Hua, J, Lehman, T J A, Harley, J B, Crow, M K
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-09-2007
• Subjects: Antibodies, Antinuclear - blood; Antibodies, Antinuclear - immunology; Autoantibodies; Autoantibodies - blood; Autoantibodies - immunology; Case-Control Studies; Cell Line; Double-stranded RNA; Female; Genetic aspects; Heritability; Humans; Interferon alpha; Interferon-alpha - blood; Interferon-alpha - genetics; Interferon-alpha - immunology; Lupus; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Male; Physiological aspects; Risk Factors; RNA-binding protein; RNA-Binding Proteins - immunology; Systemic lupus erythematosus; α-Interferon; United States
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/sj.gene.6364408

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.