Cutting edge: autoimmune disease risk variant of STAT4 confers increased sensitivity to IFN-alpha in lupus patients in vivo.
Cutting edge: autoimmune disease risk variant of STAT4 confers increased sensitivity to IFN-alpha in lupus patients in vivo.
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DOI：
10.4049/jimmunol.182.1.34
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发表时间：
2009-01-01
期刊：
影响因子：
--
通讯作者：
Niewold TB
中科院分区：
文献类型：
--
作者：
Kariuki SN;Kirou KA;MacDermott EJ;Barillas-Arias L;Crow MK;Niewold TB
干扰素-α信号增强是系统性红斑狼疮的主要致病因素。STAT4是一种受干扰素-α信号激活的转录因子，其基因变异与系统性红斑狼疮和类风湿关节炎的发病风险密切相关。我们在一个大的系统性红斑狼疮队列中检测了血清干扰素-α活性和同时干扰素-α诱导的外周血单核细胞基因表达。在系统性红斑狼疮患者中，STAT4的风险变异(T等位基因；rs7574865)同时与血清干扰素-α活性降低和干扰素-α诱导的外周血单核细胞基因表达增加有关。回归分析证实，STAT4的风险等位基因与干扰素-α信号的敏感性增加有关。干扰素调节因子5型系统性红斑狼疮危险基因与较高的血清干扰素-α活性相关，但STAT4基因对单个核细胞对血清干扰素-α的敏感性有显著影响。这些数据为体内干扰素-α途径中STAT4的风险变异体提供了生物学相关性。
Increased IFN-α signaling is a primary pathogenic factor in systemic lupus erythematosus (SLE). STAT4 is a transcription factor that is activated by IFN-α signaling, and genetic variation of STAT4 has been associated with risk of SLE and rheumatoid arthritis. We measured serum IFN-α activity and simultaneous IFN-α-induced gene expression in PBMC in a large SLE cohort. The risk variant of STAT4 (T allele; rs7574865) was simultaneously associated with both lower serum IFN-α activity and greater IFN-α-induced gene expression in PBMC in SLE patients in vivo. Regression analyses confirmed that the risk allele of STAT4 was associated with increased sensitivity to IFN-α signaling. The IFN regulatory factor 5 SLE risk genotype was associated with higher serum IFN-α activity; however, STAT4 showed dominant influence on the sensitivity of PBMC to serum IFN-α. These data provide biologic relevance for the risk variant of STAT4 in the IFN-α pathway in vivo.
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影响因子：
158.5
作者：
Remmers, Elaine F.;Plenge, Robert M.;Gregersen, Peter K.
通讯作者：
Gregersen, Peter K.
DOI：
10.1084/jem.20021553
发表时间：
2003-03-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bennett L;Palucka AK;Arce E;Cantrell V;Borvak J;Banchereau J;Pascual V
通讯作者：
Pascual V
影响因子：
56.9
作者：
Blanco, P;Palucka, AK;Banchereau, J
通讯作者：
Banchereau, J
影响因子：
--
作者：
Kirou, KA;Lee, C;Crow, MK
通讯作者：
Crow, MK
影响因子：
5
作者：
Niewold, T. B.;Hua, J.;Crow, M. K.
通讯作者：
Crow, M. K.