High serum IFN-α activity is a heritable risk factor for systemic lupus erythematosus
High serum IFN-α activity is a heritable risk factor for systemic lupus erythematosus
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DOI：
10.1038/sj.gene.6364408
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发表时间：
2007-09-01
影响因子：
5
通讯作者：
Crow, M. K.
中科院分区：
文献类型：
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作者：
Niewold, T. B.;Hua, J.;Crow, M. K.
在许多系统性红斑狼疮(SLE)患者中，干扰素-α(干扰素-α)水平升高；然而，目前尚不清楚血清中高水平的干扰素-α活性是疾病的原因还是结果。我们研究了266名SLE患者和他们的405名健康亲属，发现患者和健康亲属的血清干扰素-α活性经常高于健康无关个体。在SLE患者及其健康的一级亲属中，高干扰素-α活性在特定的家系中聚集，这表明这是一种可遗传的特征。遗传力还受到干扰素-α活性的定量家族相关性、受影响同胞对的一致性以及高干扰素-α活性特征从父母向后代频繁传递的支持。在SLE患者中，抗RNA结合蛋白和双链DNA的自身抗体与高的干扰素-α活性相关；然而，这些自身抗体在健康的家庭成员中非常罕见，不能解释观察到的家族相关性。在所有被研究的种族背景中，高干扰素-α活性的频率是相似的。这些数据表明，高血清干扰素-α活性是一种复杂的遗传性状，在SLE的发病机制中起主要作用。
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.