Pattern recognition receptor and autophagy gene variants are associated with development of antimicrobial antibodies in Crohn's disease.
Pattern recognition receptor and autophagy gene variants are associated with development of antimicrobial antibodies in Crohn's disease.
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DOI：
10.1002/ibd.22884
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发表时间：
2012-09
影响因子：
4.9
通讯作者：
Silverberg, Mark S.
中科院分区：
文献类型：
--
作者：
Murdoch, Travis B.;Xu, Wei;Stempak, Joanne M.;Landers, Carol;Targan, Stephan R.;Rotter, Jerome I.;Silverberg, Mark S.
我们试图研究参与细菌传感和自噬的基因（NOD 2，TLR 5，IRGM，ATG 16 L1）和白细胞介素-23信号通路（IL 12 B，IL 23 R，STAT 3）的变异是否与克罗恩病（CD）患者抗菌抗体的产生相关。对来自三级转诊医院（Mount Sinai Hospital，多伦多）的616例CD患者的队列进行了评价。检测DNA中的三种CD相关NOD 2变异体（3020 insC、G908 R、R702 W）、IRGM变异体、ATG 16 L1、IL 12 B、IL 23 R、STAT 3和TLR 5终止突变。通过ELISA分析血清中的抗酿酒酵母（ASCA）IgG和伊加、抗外膜蛋白C（抗ompC）、抗Cbir 1鞭毛蛋白和抗荧光假单胞菌（抗I2）。NOD 2 3020 insC与四分位数总和（p=0.003）和阳性抗体数量（p=0.02）的累积血清反应性相关。NOD 2 G908 R也与四分位数和相关（p=0.05）。ASCA血清阳性率增加与NOD 2 3020 insC（比值比（OR）= 1.9，p=0.02）和G908 R（OR=1.8，p=0.05）和ATG 16 L1 T300 A（OR=1.4，p=0.01）变异相关; ASCA阳性患者的NOD 2 3020 insC和ATG 16 L1 T300 A变异的累积数量增加（p=0.007）。TLR 5终止突变以显性阴性方式消除抗鞭毛蛋白的产生（OR=0.5，p=0.009）。IRGM CD风险变体与抗鞭毛蛋白血清阳性增加相关（OR=1.5，p=0.03）。IL 12 B、IL 23 R和STAT 3变体对抗微生物抗体的产生没有贡献。参与模式识别和自噬但不参与IL-23信号通路的先天免疫基因的变体影响CD中的抗微生物血清反应性。特别地，NOD 2 3020 insC和ATG 16 L1 T300 A的累加效应表明自噬在ASCA的发展中的作用。
We sought to investigate whether variants in genes involved in bacterial sensing and autophagy (NOD2, TLR5, IRGM, ATG16L1) and the interleukin-23 signalling pathway (IL12B, IL23R, STAT3) were associated with development of antimicrobial antibodies in patients with Crohn’s disease (CD). A cohort of 616 CD patients from a tertiary referral hospital (Mount Sinai Hospital, Toronto) was evaluated. DNA was tested for three CD-associated NOD2 variants (3020insC, G908R, R702W), variants in IRGM, ATG16L1, IL12B, IL23R, STAT3, and a TLR5-stop mutation. Serum was analyzed by ELISA for anti-Saccharomyces cervesiase (ASCA) IgG and IgA, anti-outer membrane protein C (anti-ompC), anti-Cbir1 flagellin, and anti-Pseudomonas fluorescens (anti-I2). NOD2 3020insC was associated with cumulative seroreactivity by quartile sum (p=0.003) and number of positive antibodies (p=0.02). NOD2 G908R was also associated with quartile sum (p=0.05). Increased ASCA seropositivity was associated with NOD2 3020insC (odds ratio (OR)= 1.9, p=0.02) and G908R (OR=1.8, p=0.05), and ATG16L1 T300A (OR=1.4, p=0.01) variants; ASCA positive patients had an increased cumulative number of NOD2 3020insC and ATG16L1 T300A variants (p=0.007). TLR5-stop mutation abrogated development of anti-flagellin in a dominant-negative fashion (OR=0.5, p=0.009). The IRGM CD risk variant was associated with increased anti-flagellin seropositivity (OR=1.5, p=0.03). IL12B, IL23R, and STAT3 variants did not contribute to development of anti-microbial antibodies. Variants in innate immune genes involved in pattern recognition and autophagy but not the IL-23 signaling pathway influence antimicrobial seroreactivity in CD. In particular, the additive effect of NOD2 3020insC and ATG16L1 T300A suggests a role for autophagy in development of ASCA.
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影响因子：
32.4
作者：
Oppmann, B;Lesley, R;Kastelein, RA
通讯作者：
Kastelein, RA
一种常见的主导TLR5停止密码子多态性废除了鞭毛蛋白信号传导，并与对军团疾病的易感性有关。
影响因子：
15.3
作者：
Hawn, TR;Verbon, A;Lettinga, KD;Zhao, LP;Li, SS;Laws, RJ;Skerrett, SJ;Beutler, B;Schroeder, L;Nachman, A;Ozinsky, A;Smith, KD;Aderem, A
通讯作者：
Aderem, A
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Hampe, Jochen;Franke, Andre;Schreiber, Stefan
通讯作者：
Schreiber, Stefan
影响因子：
29.4
作者：
Landers, CJ;Cohavy, O;Targan, SR
通讯作者：
Targan, SR