Abstract
Interferon α (IFN-α) levels are elevated in many patients with systemic lupus erythematosus (SLE); however it is not known whether high serum IFN-α 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-α activity in both patients and healthy relatives as compared to healthy unrelated individuals. High IFN-α 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-α activity, concordance in affected sib pairs and frequent transmission of the high IFN-α activity trait from parents to offspring. Autoantibodies to RNA-binding proteins and double-stranded DNA were associated with high IFN-α 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-α activity was similar across all studied ethnic backgrounds. These data suggest that high serum IFN-α activity is a complex heritable trait, which plays a primary role in SLE pathogenesis.
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Acknowledgements
We acknowledge Karen Onel and Kenan Onel for their contribution in establishing the Hospital for Special Surgery Family Lupus registry, and Marie Flesch for her assistance in obtaining materials from the Lupus Multiplex Registry and Repository at Oklahoma Medical Research Foundation. The Hospital for Special Surgery Family Lupus Registry was established with support from the S.L.E. Foundation, Inc. and the Toys-R-Us Foundation. The Lupus Multiplex Registry and Repository is supported by NIH NIAMS AR-5-2221 to JBH TBN received salary support from NIH T32 AR07517 and NIAID Clinical Research Loan Repayment grants. This work was supported by the NIH (AI059893) and research grants from the Alliance for Lupus Research, the Lupus Research Institute and the Mary Kirkland Center for Lupus Research to MKC.
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TB Niewold – NIH T32 AR07517, NIAID Clinical Research Loan Repayment; J Hua – patent pending for interferon assay; TJA Lehman – none; JB Harley – Lupus Multiplex Registry and Repository – NIH NIAMS AR-5-2221; MK Crow – patent pending for interferon assay, NIH R01 AI05983-01, Research Grants from Alliance for Lupus Research, Mary Kirkland Center for Lupus Research and Lupus Research Institute; Support for HSS Family Lupus Registry – Toys ‘R Us Foundation and SLE Foundation.
Supplementary Information accompanies the paper on Genes and Immunity web site (http://www.nature.com/gene)
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Niewold, T., Hua, J., Lehman, T. et al. High serum IFN-α activity is a heritable risk factor for systemic lupus erythematosus. Genes Immun 8, 492–502 (2007). https://doi.org/10.1038/sj.gene.6364408
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DOI: https://doi.org/10.1038/sj.gene.6364408
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