Granulocyte-macrophage colony-stimulating factor autoantibodies: a marker of aggressive Crohn's disease.
Granulocyte-macrophage colony-stimulating factor autoantibodies: a marker of aggressive Crohn's disease.
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DOI：
10.1097/mib.0b013e318281f506
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发表时间：
2013-07
影响因子：
4.9
通讯作者：
Denson LA
中科院分区：
文献类型：
--
作者：
Gathungu G;Kim MO;Ferguson JP;Sharma Y;Zhang W;Ng SM;Bonkowski E;Ning K;Simms LA;Croft AR;Stempak JM;Walker N;Huang N;Xiao Y;Silverberg MS;Trapnell B;Cho JH;Radford-Smith GL;Denson LA
在一个以儿科患者为主的队列中（总共 394 例，成人 CD 57 例），针对粒细胞巨噬细胞集落刺激因子 (GM-CSF Ab) 的中和自身抗体 (Ab) 与回肠克罗恩病 (CD) 狭窄相关。本研究的目的是在两个独立的主要成人炎症性肠病患者队列中检查这种关联。对来自 NIDDK IBD 遗传学联盟的 745 名受试者和来自澳大利亚的 737 名患者的血清样本进行了 GM-CSF Ab 和遗传标记的分析。我们进行了向后消除的多元回归分析，以评估 GM-CSF Ab 水平、确定的 CD 风险等位基因和吸烟对来自两个队列的 477 名合并 CD 受试者的回肠疾病位置的贡献。我们还确定了两个队列中合并 CD 受试者的 GM-CSF Ab 水平与需要手术干预的并发症的关联。与每个队列中的溃疡性结肠炎或对照相比，CD 患者的血清样本表达的 GM-CSF Ab 浓度显着更高。在澳大利亚队列中，患有回肠 CD 的非吸烟者表达出显着更高的 GM-CSF Ab 浓度 (p = 0.002)。 GM-CSF Ab 升高、回肠疾病部位和疾病持续时间超过 3 年与 CD 的狭窄/穿透行为和肠道切除独立相关。 GM-CSF Ab 的高表达是侵袭性 CD 行为和包括手术在内的并发症的风险标志。改变因素包括吸烟环境暴露和遗传风险标记。
Neutralizing auto-antibodies (Ab) against granulocyte-macrophage colony-stimulating factor (GM-CSF Ab) have been associated with stricturing ileal Crohn’s disease (CD) in a largely pediatric patient cohort (total 394, adult CD 57). The aim of this study was to examine this association in two independent predominantly adult inflammatory bowel disease patient cohorts. Serum samples from 745 subjects from the NIDDK IBD Genetics Consortium and 737 patients from Australia were analyzed for GM-CSF Ab and genetic markers. We conducted multiple regression analysis with backwards elimination to assess the contribution of GM-CSF Ab levels, established CD risk alleles and smoking on ileal disease location in the 477 combined CD subjects from both cohorts. We also determined associations of GM-CSF Ab levels with complications requiring surgical intervention in combined CD subjects in both cohorts. Serum samples from CD patients expressed significantly higher concentrations of GM-CSF Ab when compared to Ulcerative Colitis or controls in each cohort. Non-smokers with ileal CD expressed significantly higher GM-CSF Ab concentrations in the Australian cohort (p= 0.002). Elevated GM-CSF Ab, ileal disease location and disease duration greater than 3 years were independently associated with stricturing/penetrating behavior and intestinal resection for CD. The expression of high GM-CSF Ab is a risk marker for aggressive CD behavior and complications including surgery. Modifying factors include environmental exposure to smoking and genetic risk markers.