title: Granulocyte-macrophage colony-stimulating factor autoantibodies: a marker of aggressive Crohn's disease.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pediatric Gastroenterology, Stony Brook University Hospital, Stony Brook, NY 11794, USA. grace.gathungu@stonybrook.edu
authors.forename: Grace
authors.initials: G
authors.lastname: Gathungu
authors.forename: Mi-Ok
authors.initials: MO
authors.lastname: Kim
authors.forename: John P
authors.initials: JP
authors.lastname: Ferguson
authors.forename: Yashoda
authors.initials: Y
authors.lastname: Sharma
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Sok Meng E
authors.initials: SM
authors.lastname: Ng
authors.forename: Erin
authors.initials: E
authors.lastname: Bonkowski
authors.forename: Kaida
authors.initials: K
authors.lastname: Ning
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Simms
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Croft
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Stempak
authors.forename: Nicole
authors.initials: N
authors.lastname: Walker
authors.forename: Ning
authors.initials: N
authors.lastname: Huang
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiao
authors.forename: Mark S
authors.initials: MS
authors.lastname: Silverberg
authors.forename: Bruce
authors.initials: B
authors.lastname: Trapnell
authors.forename: Judy H
authors.initials: JH
authors.lastname: Cho
authors.forename: Graham L
authors.initials: GL
authors.lastname: Radford-Smith
authors.forename: Lee A
authors.initials: LA
authors.lastname: Denson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003251:Constriction, Pathologic / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D003424:Crohn Disease / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D005260:Female; D005500:Follow-Up Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007415:Intestinal Obstruction / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D016178:Granulocyte-Macrophage Colony-Stimulating Factor