Division of Pediatric Gastroenterology, Stony Brook University Hospital, Stony Brook, NY 11794, USA.
Inflamm Bowel Dis. 2013 Jul;19(8):1671-80. doi: 10.1097/MIB.0b013e318281f506.
Neutralizing autoantibodies (Abs) 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 2 independent predominantly adult inflammatory bowel disease patient cohorts.
Serum samples from 742 subjects from the NIDDK IBD Genetics Consortium and 736 subjects from Australia were analyzed for GM-CSF Ab and genetic markers. We conducted multiple regression analysis with backward elimination to assess the contribution of GM-CSF Ab levels and 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 patients with CD expressed significantly higher concentrations of GM-CSF Ab when compared with ulcerative colitis or controls in each cohort. Nonsmokers 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 more 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.
针对粒细胞-巨噬细胞集落刺激因子（GM-CSF Ab）的中和抗体与狭窄性回肠克罗恩病（CD）有关，这在很大程度上是在儿科患者队列中观察到的（总计 394 例，成人 CD 57 例）。本研究的目的是在两个独立的主要为成人炎症性肠病患者队列中检验这种关联。
分析了来自 NIDDK IBD 遗传学联合会的 742 名受试者和来自澳大利亚的 736 名受试者的血清样本，以检测 GM-CSF Ab 和遗传标记物。我们进行了多元回归分析，采用向后消除法，以评估 GM-CSF Ab 水平以及已建立的 CD 风险等位基因和吸烟对来自两个队列的 477 例合并 CD 受试者回肠疾病部位的影响。我们还确定了 GM-CSF Ab 水平与两个队列中合并 CD 受试者需要手术干预的并发症之间的关联。
与溃疡性结肠炎或对照组相比，来自每个队列的 CD 患者的血清样本表达了显著更高浓度的 GM-CSF Ab。在澳大利亚队列中，非吸烟者的回肠 CD 表达了显著更高的 GM-CSF Ab 浓度（P = 0.002）。升高的 GM-CSF Ab、回肠疾病部位和病程超过 3 年与狭窄/穿透性行为以及 CD 的肠切除术独立相关。
高 GM-CSF Ab 的表达是 CD 侵袭性行为和并发症的风险标志物，包括手术。修饰因子包括环境暴露于吸烟和遗传风险标志物。
