Impaired granulocyte-macrophage colony-stimulating factor bioactivity accelerates surgical recurrence in ileal crohn's disease

作     者：Grace Gathungu Yuanhao Zhang Xinyu Tian Erin Bonkowski Leahana Rowehl Julia Krumsiek Billy Nix Claudia Chalk Bruce Trapnell Wei Zhu Rodney Newberry Lee Denson Ellen Li 

作者机构：Department of Pediatrics Division of Pediatric Gastroenterology Stony Brook University Department of Medicine Division of Gastroenterology Stony Brook University Department of Pediatrics Cincinnati Children’s Hospital Medical Center Department of Medicine Washington University St.Louis Applied Mathematics and Statistics Stony Brook University 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2018年第24卷第5期

页      面：623-630页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Supported by(in part)the National Institutes of Health No.R01 DK098231 R01 DK078683 and No.P30DK052574 

主　　题：Inflammatory bowel disease granulocytemacrophage colony-stimulating factor antibody Crohn’s disease surgery 

摘      要：AIM To examine the relationship between elevated granulocyte-macrophage colony-stimulating factor(GMCSF) auto-antibodies(Ab) level and time to surgical recurrence after initial surgery for Crohn s disease(CD). METHODS We reviewed 412 charts from a clinical database at tertiary academic hospital. Patients included in the study had ileal or ileocolonic CD and surgical resection of small bowel or ileocecal region for management of disease. Serum samples were analyzed for serological assays including GM-CSF cytokine, GM-CSF Ab, ASCA Ig G and Ig A, and genetic markers including SNPs rs2066843, rs2066844, rs2066845, rs2076756 and rs2066847 in NOD2, rs2241880 in ATG16 L1, and rs13361189 in IRGM. Cox proportional-hazards models were used to assess the predictors of surgical *** Ninety six percent of patients underwent initial ileocecal resection(ICR) or ileal resection(IR) and subsequently 40% of patients required a second ICR/IR for CD. GMCSF Ab level was elevated at a median of 3.81 mcg/mL. Factors predicting faster time to a second surgery included elevated GM-CSF Ab [hazard ratio(HR) 3.52, 95%CI: 1.45-8.53, P = 0.005] and elevated GM-CSF cytokine(HR = 2.48, 95%CI: 1.31-4.70, P = 0.005). Factors predicting longer duration between first and second surgery included use of Immunomodulators(HR = 0.49, 95%CI: 0.31-0.77, P = 0.002), the interaction effect of low GM-CSF Ab levels and smoking(HR = 0.60, 95%CI: 0.45-0.81, P = 0.001) and the interaction effect of low GM-CSF cytokine levels and ATG16 L1(HR = 0.65, 95%CI: 0.49-0.88, P = 0.006).CONCLUSION GM-CSF bioavailability plays a critical role in maintaining intestinal homeostasis. Decreased bioavailability coupled with the genetic risk markers and/or smoking results in aggressive CD behavior.