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Skip Navigation LinksHome > July 2013 - Volume 19 - Issue 8 > Granulocyte-Macrophage Colony-Stimulating Factor Autoantibod...
Inflammatory Bowel Diseases:
doi: 10.1097/MIB.0b013e318281f506
Original Clinical Articles

Granulocyte-Macrophage Colony-Stimulating Factor Autoantibodies: A Marker of Aggressive Crohn's Disease

Gathungu, Grace MD*; Kim, Mi-Ok PhD; Ferguson, John P. PhD; Sharma, Yashoda PhD; Zhang, Wei MD, PhD; Ng, Sok Meng E. BS; Bonkowski, Erin MD§; Ning, Kaida MS; Simms, Lisa A. BSc‖,¶; Croft, Anthony R. MBBS; Stempak, Joanne M. MSc**; Walker, Nicole BMed; Huang, Ning MAppScl; Xiao, Yang PhD††; Silverberg, Mark S. MD, PhD**; Trapnell, Bruce MD‡‡; Cho, Judy H. MD‡,§§; Radford-Smith, Graham L. MB, BCh, PhD‖,¶; Denson, Lee A. MD§

Supplemental Author Material
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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.

Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.

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