Brief Report: IRF5 systemic lupus erythematosus risk haplotype is associated with asymptomatic serologic autoimmunity and progression to clinical autoimmunity in mothers of children with neonatal lupus.
Brief Report: IRF5 systemic lupus erythematosus risk haplotype is associated with asymptomatic serologic autoimmunity and progression to clinical autoimmunity in mothers of children with neonatal lupus.
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DOI：
10.1002/art.34571
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发表时间：
2012-10
影响因子：
--
通讯作者：
Niewold, Timothy B.
中科院分区：
文献类型：
--
作者：
Cherian, Tharian S.;Kariuki, Silvia N.;Franek, Beverly S.;Buyon, Jill P.;Clancy, Robert M.;Niewold, Timothy B.
干扰素调节因子5 （IRF5）的遗传变异与发生系统性红斑狼疮（SLE）的风险相关，这种关联在很大程度上依赖于抗ro自身抗体。我们研究了一组不同诊断的抗ro阳性个体，以确定IRF5基因型是否与母体诊断或自身免疫进展相关。我们对新生儿狼疮研究登记处招募的93名欧洲血统受试者进行了IRF5单倍型标记多态性基因分型，这些受试者都具有高滴度的抗ro自身抗体，并且患有新生儿狼疮（NL），并将等位基因频率与非自身免疫性对照进行了比较。母亲的诊断包括SLE、干燥综合征（SS）、未分化自身免疫综合征（UAS）和无症状。除SS外，所有抗ro阳性受试者中IRF5的sled风险单倍型均富集（OR = 2.55, p=8.8×10−4）。即使是无症状的抗ro抗体个体也富含sled风险单倍型（OR=2.69, p=0.019）。同一单倍型在最初无症状，但在随访期间出现症状性SLE的受试者中更为普遍（OR=5.83, p=0.0024）。有趣的是，SS与两个较小的IRF5单倍型相关，并且这些相同的单倍型在SLE和UAS患者中频率降低。IRF5 SLE风险单倍型与无症状个体的抗ro抗体以及无症状抗ro阳性个体的SLE进展相关。NL母亲的SS与不同的IRF5单倍型相关。这些数据表明，IRF5多态性在人类血清学自身免疫中发挥作用，并可能促进临床自身免疫的进展。
Genetic variation in interferon regulatory factor 5 (IRF5) has been associated with risk of developing systemic lupus erythematosus (SLE), and this association is largely dependent upon anti-Ro autoantibodies. We studied a unique cohort of anti-Ro positive individuals with diverse diagnoses to determine if IRF5 genotype associated with maternal diagnosis or progression of autoimmunity. We genotyped haplotype-tagging polymorphisms in IRF5 in 93 European ancestry subjects recruited to the Research Registry for Neonatal Lupus who all had high titer anti-Ro autoantibodies and a child with neonatal lupus (NL), and allele frequencies were compared to non-autoimmune controls. The mothers diagnoses included SLE, Sjogren’s syndrome (SS), undifferentiated autoimmune syndrome (UAS), and asymptomatic. The SLE-risk haplotype of IRF5 was enriched in all anti-Ro positive subjects except those with SS (OR = 2.55, p=8.8×10−4). Even asymptomatic individuals with anti-Ro antibodies were enriched for the SLE-risk haplotype (OR=2.69, p=0.019). The same haplotype was more prevalent in subjects who were initially asymptomatic, but developed symptomatic SLE during follow up (OR=5.83, p=0.0024). Interestingly, SS was associated with two minor IRF5 haplotypes, and these same haplotypes were decreased in frequency in those with SLE and UAS. The IRF5 SLE-risk haplotype was associated with anti-Ro antibodies in asymptomatic individuals as well as progression to SLE in asymptomatic anti-Ro positive individuals. SS in NL mothers was associated with different IRF5 haplotypes. These data suggest that IRF5 polymorphisms play a role in serologic autoimmunity in humans and may promote the progression to clinical autoimmunity.
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影响因子：
27.4
作者：
Rivera, T. L.;Izmirly, P. M.;Buyon, J. P.
通讯作者：
Buyon, J. P.
DOI：
10.4049/jimmunol.0901748
发表时间：
2010-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Richez C;Yasuda K;Bonegio RG;Watkins AA;Aprahamian T;Busto P;Richards RJ;Liu CL;Cheung R;Utz PJ;Marshak-Rothstein A;Rifkin IR
通讯作者：
Rifkin IR
DOI：
10.1016/s0735-1097(98)00161-2
发表时间：
1998-06-01
影响因子：
24
作者：
Buyon, JP;Hiebert, R;Skovron, ML
通讯作者：
Skovron, ML
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：
5
作者：
Nordmark, G.;Kristjansdottir, G.;Syvanen, A-C
通讯作者：
Syvanen, A-C