1. ¹Mary Kirkland Center for Lupus Research, Hospital for Special Surgery, New York, NY, USA
2. ²Oklahoma Medical Research Foundation, Oklahoma City, OK, USA

Correspondence: Dr TB Niewold, Section of Rheumatology, University of Chicago, 5841 S Maryland Avenue MC0930, Chicago, IL 60637, USA. E-mail: niewoldt@hss.edu

Received 2 April 2007; Accepted 16 May 2007; Published online 21 June 2007.

Abstract

Interferon (IFN-) levels are elevated in many patients with systemic lupus erythematosus (SLE); however it is not known whether high serum IFN- 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- activity in both patients and healthy relatives as compared to healthy unrelated individuals. High IFN- 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- activity, concordance in affected sib pairs and frequent transmission of the high IFN- activity trait from parents to offspring. Autoantibodies to RNA-binding proteins and double-stranded DNA were associated with high IFN- 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- activity was similar across all studied ethnic backgrounds. These data suggest that high serum IFN- activity is a complex heritable trait, which plays a primary role in SLE pathogenesis.