Granulocyte-macrophage colony-stimulating factor autoantibodies: a marker of aggressive Crohn's disease

Inflamm Bowel Dis. 2013 Jul;19(8):1671-80. doi: 10.1097/MIB.0b013e318281f506.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Biomarkers / blood*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Constriction, Pathologic / blood
  • Constriction, Pathologic / diagnosis*
  • Constriction, Pathologic / etiology
  • Crohn Disease / blood
  • Crohn Disease / complications
  • Crohn Disease / diagnosis*
  • Female
  • Follow-Up Studies
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Infant
  • Infant, Newborn
  • Intestinal Obstruction / blood
  • Intestinal Obstruction / diagnosis*
  • Intestinal Obstruction / etiology
  • Male
  • Middle Aged
  • Prognosis
  • Risk Factors
  • Young Adult


  • Autoantibodies
  • Biomarkers
  • Granulocyte-Macrophage Colony-Stimulating Factor