Genetic variation near IRF8 is associated with serologic and cytokine profiles in systemic lupus erythematosus and multiple sclerosis.
Genetic variation near IRF8 is associated with serologic and cytokine profiles in systemic lupus erythematosus and multiple sclerosis.
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DOI：
10.1038/gene.2013.42
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发表时间：
2013-12
影响因子：
5
通讯作者：
Niewold, T. B.
中科院分区：
文献类型：
--
作者：
Chrabot, B. S.;Kariuki, S. N.;Zervou, M. I.;Feng, X.;Arrington, J.;Jolly, M.;Boumpass, D. T.;Reder, A. T.;Goulielmos, G. N.;Niewold, T. B.
IRF8等位基因与系统性红斑狼疮（SLE）和多发性硬化症（MS）的易感性相关。虽然高I型干扰素（IFN）被认为是SLE的病因，但I型IFN被用作MS的治疗方法。我们研究了IRF8等位基因是否与SLE和MS的I型IFN水平或血清学特征相关，先前与SLE或MS相关的等位基因在SLE和MS患者中进行了基因分型。ms相关的rs17445836G等位基因与SLE患者的抗dsdna自身抗体相关（meta分析OR=1.92）。该等位基因与抗dsdna抗体SLE患者血清IFN活性降低以及抗dsdna阴性SLE患者PBMC中I型IFN诱导基因表达降低相关。在继发性进展性MS患者中，rs17445836G与血清I型IFN降低相关。Rs17445836G与SLE患者B细胞中IRF8表达增加相关。总之，IRF8 rs17445836G与以I型IFN水平低为特征的人类自身免疫性疾病相关，这可能具有药物遗传学相关性，因为I型IFN在SLE和ms中受到调节。与自身抗体和B细胞中IRF8表达增加的关联支持rs17445836G在体液耐受性中的作用。
Alleles of IRF8 are associated with susceptibility to both systemic lupus erythematosus (SLE) and multiple sclerosis (MS). While high type I interferon (IFN) is thought to be causal in SLE, type I IFN is used as a therapy in MS. We investigated whether IRF8 alleles were associated with type I IFN levels or serologic profiles in SLE and MS. Alleles which have been previously associated with SLE or MS were genotyped in SLE and MS patients. The MS-associated rs17445836G allele was associated with anti-dsDNA autoantibodies in SLE patients (meta-analysis OR=1.92). The same allele was associated with decreased serum IFN activity in SLE patients with anti-dsDNA antibodies, and with decreased type I IFN-induced gene expression in PBMC from anti-dsDNA negative SLE patients. In secondary progressive MS patients, rs17445836G was associated with decreased serum type I IFN. Rs17445836G was associated with increased IRF8 expression in SLE patient B cells. In summary, IRF8 rs17445836G is associated with human autoimmune disease characterized by low type I IFN levels, and this may have pharmacogenetic relevance as type I IFN is modulated in SLE and MS. The association with autoantibodies and increased IRF8 expression in B cells supports a role for rs17445836G in humoral tolerance.
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DOI：
10.4049/jimmunol.182.1.34
发表时间：
2009-01-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kariuki SN;Kirou KA;MacDermott EJ;Barillas-Arias L;Crow MK;Niewold TB
通讯作者：
Niewold TB
影响因子：
5.1
作者：
Niewold, Timothy B.;Kariuki, Silvia N.;Pachman, Lauren M.
通讯作者：
Pachman, Lauren M.
影响因子：
--
作者：
Kariuki SN;Franek BS;Mikolaitis RA;Utset TO;Jolly M;Skol AD;Niewold TB
通讯作者：
Niewold TB
影响因子：
27.4
作者：
Niewold TB;Kelly JA;Kariuki SN;Franek BS;Kumar AA;Kaufman KM;Thomas K;Walker D;Kamp S;Frost JM;Wong AK;Merrill JT;Alarcón-Riquelme ME;Tikly M;Ramsey-Goldman R;Reveille JD;Petri MA;Edberg JC;Kimberly RP;Alarcón GS;Kamen DL;Gilkeson GS;Vyse TJ;James JA;Gaffney PM;Moser KL;Crow MK;Harley JB
通讯作者：
Harley JB
影响因子：
--
作者：
Harley, Isaac T. W.;Niewold, Timothy B.;James, Judith A.
通讯作者：
James, Judith A.