Published online Feb 7, 2018. doi: 10.3748/wjg.v24.i5.623
Peer-review started: November 16, 2017
First decision: November 30, 2017
Revised: December 5, 2017
Accepted: December 12, 2017
Article in press: December 12, 2017
Published online: February 7, 2018
Processing time: 77 Days and 5 Hours
To examine the relationship between elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) auto-antibodies (Ab) level and time to surgical recurrence after initial surgery for Crohn’s disease (CD).
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 IgG and IgA, and genetic markers including SNPs rs2066843, rs2066844, rs2066845, rs2076756 and rs2066847 in NOD2, rs2241880 in ATG16L1, and rs13361189 in IRGM. Cox proportional-hazards models were used to assess the predictors of surgical recurrence.
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. GM-CSF 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 ATG16L1 (HR = 0.65, 95%CI: 0.49-0.88, P = 0.006).
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.
Core tip: This retrospective study assesses the risk of surgery for management of ileal Crohn’s disease (CD) among patients with elevated granulocyte-macrophage colony-stimulating factor (GM-CSF) auto-antibodies (Ab). In this cohort, 396 subjects underwent initial ileocecal resection or ileal resection for management of disease. Subsequently 165 patients (41.7%) required a second ICR or IR. Factors predicting faster time to a second surgery were elevated GM-CSF Ab and elevated GM-CSF cytokine. Patients with low GM-CSF cytokine levels and the protective allele for ATG16L1 had longer intervals between a first and second surgery. To improve long term outcomes for patients with Ileal CD we need to optimize therapeutic options for patients with low GM-CSF bioavailability and genetic risk markers for ATG16L1.