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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§

doi: 10.1097/MIB.0b013e318281f506
Original Clinical Articles

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.

Article first published online 6 June 2013Supplemental Digital Content is Available in the Text.

*Division of Pediatric Gastroenterology, Stony Brook University Hospital, Stony Brook, New York;

Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio;

Department of Medicine, Section of Digestive Diseases, Yale University School of Medicine, New Haven, Connecticut;

§Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio;

Division of Inflammatory Bowel Diseases, Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Australia;

Department of Gastroenterology, Royal Brisbane and Women’s Hospital, Brisbane, Australia;

**IBD Research Unit, Zane Cohen Centre, Mount Sinai Hospital, Toronto, Ontario, Canada;

††Department of Mathematical Sciences, University of Cincinnati, Cincinnati, Ohio;

‡‡Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio; and

§§Department of Genetics, Yale University School of Medicine, New Haven, Connecticut.

Reprints: Grace Gathungu, MD, Division of Pediatric Gastroenterology, Stony Brook University Hospital, HSC T11-080, Stony Brook, NY 11794 (e-mail:

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Supported in part by the National Institutes of Health grants U01DK 062422-08 S1, R01DK078683-03, NIDDK U01 DK062429 (J.H.C.), U01 DK062422 (J.H.C.), and R01HL085453.

Judy H. Cho is a medical consultant for Pfizer. All remaining authors have nothing to disclose.

Received November 01, 2012

Accepted November 6, 2012

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