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IL-10 polymorphisms +434T/C, +504G/T, and -2849C/T may predispose to tubulointersititial nephritis and uveitis in pediatric population.白细胞介素-10 多态性 +434T/C、+504G/T 和-2849C/T 可能使儿科人群易患小管间质性肾炎和葡萄膜炎。
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本文引用的文献

1
TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis.TNF 受体 1 遗传风险与多发性硬化症的抗 TNF 治疗结果相吻合。
Nature. 2012 Aug 23;488(7412):508-511. doi: 10.1038/nature11307.
2
Punctate inner choroidopathy and multifocal choroiditis with panuveitis share haplotypic associations with IL10 and TNF loci.点状内层脉络膜病变和多灶性脉络膜炎伴全葡萄膜炎与 IL10 和 TNF 基因座具有单体型关联。
Invest Ophthalmol Vis Sci. 2011 Jun 1;52(6):3573-81. doi: 10.1167/iovs.10-6743.
3
-308 G > A of TNF-α gene promoter decreases the risk of multiple sclerosis: a meta-analysis.TNF-α 基因启动子 308G > A 降低多发性硬化症风险：一项荟萃分析。
Mult Scler. 2011 Jun;17(6):658-65. doi: 10.1177/1352458510394009. Epub 2010 Dec 22.
4
[Manifestation of multiple sclerosis under treatment with infliximab for intermediate uveitis].[英夫利昔单抗治疗中间葡萄膜炎时的多发性硬化表现]
Nervenarzt. 2011 Apr;82(4):509-10. doi: 10.1007/s00115-010-3191-5.
5
The polymorphisms of the TNF-α gene in multiple sclerosis?--a meta-analysis.TNF-α 基因多态性与多发性硬化症的相关性——一项荟萃分析。
Mol Biol Rep. 2011 Aug;38(6):4137-44. doi: 10.1007/s11033-010-0533-0. Epub 2010 Dec 7.
6
Optic neuritis associated with adalimumab in the treatment of uveitis.与阿达木单抗治疗葡萄膜炎相关的视神经炎。
Ocul Immunol Inflamm. 2010 Dec;18(6):475-81. doi: 10.3109/09273948.2010.495814. Epub 2010 Sep 1.
7
Infliximab-induced demyelination causes visual disturbance mistaken for recurrence of HLA-B27-related uveitis.英夫利昔单抗诱导的脱髓鞘导致视功能障碍，误诊为 HLA-B27 相关葡萄膜炎复发。
Ocul Immunol Inflamm. 2010 Dec;18(6):482-4. doi: 10.3109/09273948.2010.496914. Epub 2010 Aug 25.
8
Cytokine polymorphism in noninfectious uveitis.细胞因子多态性与非感染性葡萄膜炎。
Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4133-42. doi: 10.1167/iovs.09-4583. Epub 2010 Mar 24.
9
Immunomodulation by semi-mature dendritic cells: a novel role of Toll-like receptors and interleukin-6.半成熟树突状细胞的免疫调节作用：Toll 样受体和白细胞介素-6的新作用。
Int J Med Microbiol. 2010 Jan;300(1):19-24. doi: 10.1016/j.ijmm.2009.08.010. Epub 2009 Sep 24.
10
Induction of Treg by monocyte-derived DC modulated by vitamin D3 or dexamethasone: differential role for PD-L1.维生素 D3 或地塞米松调节的单核细胞来源的树突状细胞诱导 Treg：PD-L1 的差异作用。
Eur J Immunol. 2009 Nov;39(11):3147-59. doi: 10.1002/eji.200839103.

与肿瘤坏死因子产生相关的肿瘤坏死因子多态性影响特发性中间葡萄膜炎的风险。

Tumor necrosis factor polymorphisms associated with tumor necrosis factor production influence the risk of idiopathic intermediate uveitis.

作者信息

Atan Denize, Heissigerova Jarka, Kuffová Lucia, Hogan Aideen, Kilmartin Dara J, Forrester John V, Bidwell Jeff L, Dick Andrew D, Churchill Amanda J

机构信息

School of Clinical Sciences, Bristol Eye Hospital, Lower Maudlin Street, Bristol, BS1 2LX, United Kingdom.

出版信息

Mol Vis. 2013;19:184-95. Epub 2013 Jan 28.

PMID:23378732
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3559088/
Abstract

PURPOSE

Idiopathic intermediate uveitis (IIU) is a potentially sight-threatening inflammatory disorder with well-defined anatomic diagnostic criteria. It is often associated with multiple sclerosis, and both conditions are linked to HLA-DRB1*15. Previously, we have shown that non-infectious uveitis (NIU) is associated with interleukin 10 (IL10) polymorphisms, IL10-2849A (rs6703630), IL10+434T (rs2222202), and IL10+504G (rs3024490), while a LTA+252AA/TNFA-238GG haplotype (rs909253/rs361525) is protective. In this study, we determined whether patients with IIU have a similar genetic profile as patients with NIU or multiple sclerosis.

METHODS

Twelve polymorphisms were genotyped, spanning the tumor necrosis factor (TNF) and IL10 genomic regions, in 44 patients with IIU and 92 population controls from the UK and the Republic of Ireland.

RESULTS

IIU was strongly associated with the TNFA-308A and TNFA-238A polymorphisms. We found the combination of TNFA-308 and -238 loci was more strongly associated with IIU than any other loci across the major histocompatibility complex, including HLA-DRB1.

CONCLUSIONS

TNF polymorphisms, associated with increased TNF production, are highly associated with IIU. These results offer the potential to ascribe therapeutic response and risk (i.e., the influence of HLA-DRB1*15 status and TNFR1 polymorphism) to anti-TNF therapy in IIU.

摘要

目的

特发性中间葡萄膜炎（IIU）是一种具有明确解剖学诊断标准的潜在致盲性炎症性疾病。它常与多发性硬化症相关，且这两种疾病均与HLA - DRB1*15相关。此前，我们已表明非感染性葡萄膜炎（NIU）与白细胞介素10（IL10）多态性、IL10 - 2849A（rs6703630）、IL10 + 434T（rs2222202）和IL10 + 504G（rs3024490）相关，而LTA + 252AA/TNFA - 238GG单倍型（rs909253/rs361525）具有保护作用。在本研究中，我们确定IIU患者是否具有与NIU患者或多发性硬化症患者相似的基因特征。

方法

对来自英国和爱尔兰共和国的44例IIU患者和92名人群对照进行了12种多态性的基因分型，这些多态性跨越肿瘤坏死因子（TNF）和IL10基因组区域。

结果

IIU与TNFA - 308A和TNFA - 238A多态性密切相关。我们发现TNFA - 308和 - 238位点的组合与IIU的相关性比主要组织相容性复合体中的任何其他位点都更强，包括HLA - DRB1。

结论

与TNF产生增加相关的TNF多态性与IIU高度相关。这些结果为将IIU抗TNF治疗的治疗反应和风险（即HLA - DRB1*15状态和TNFR1多态性的影响）归因提供了可能性。