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: Grace Gathungu, Mi-Ok Kim, John P Ferguson, Yashoda Sharma, Wei Zhang, Sok Meng E Ng, Erin Bonkowski, Kaida Ning, Lisa A Simms, Anthony R Croft, Joanne M Stempak, Nicole Walker, Ning Huang, Yang Xiao, Mark S Silverberg, Bruce Trapnell, Judy H Cho, Graham L Radford-Smith, Lee A Denson
• Journal: Inflammatory bowel diseases (Inflamm Bowel Dis) Vol. 19 Issue 8 Pg. 1671-80 (Jul 2013) ISSN: 1536-4844 [Electronic] England
• PMID: 23749272 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

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

Topics

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