High Serum IFN-alpha Activity is a Heritable Risk Factor for Systemic Lupus Erythematosus

Overview

Journal Genes Immun

Date 2007 Jun 22

PMID 17581626

Citations 234

Authors

T B Niewold

J Hua

T J A Lehman

J B Harley

M K Crow

Affiliations

Soon will be listed here.

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.

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