title: Increased prevalence of luminal narrowing and stricturing identified by enterography in pediatric Crohn's disease patients with elevated granulocyte-macrophage colony stimulating factor autoantibodies.
abstract: BACKGROUND
  Crohn's disease (CD) patients with elevated granulocyte-macrophage colony-stimulating factor autoantibodies (GM-CSF Ab) are more likely to develop stricturing behavior requiring surgery. Computed tomography or magnetic resonance enterography (CTE or MRE) may detect luminal narrowing (LN) before stricture development. The objective of this study was to determine whether CD patients with elevated GM-CSF Ab (≥1.6 μg/mL) have a higher prevalence of LN and stricturing on CTE or MRE.
  
  
  METHODS
  A single-center, cross-sectional study of 153 pediatric patients with CD and control subjects undergoing diagnostic CTE or MRE. Examinations were evaluated for disease activity using a novel scoring system and for the presence of LN, stricture, intra-abdominal abscess, or fistulae. Dichotomous outcomes were compared with respect to antibody status (high or low) using Fisher's exact test and logistic regression, whereas continuous outcomes were evaluated using unpaired t test.
  
  
  RESULTS
  GM-CSF Ab were elevated in CD patients (n = 114) with a median (interquartile range) GM-CSF Ab level of 2.3 μg/mL (0.5-6.6 μg/mL) compared with 0.6 μg/mL (0.3-1.3 μg/mL) in healthy and disease control subjects (n = 39) (P = 0.001). Ileal disease location was more common in CD patients with high GM-CSF Ab (P < 0.001). LN increased from 39% in CD patients with low GM-CSF Ab to 71% in those with high levels (P = 0.004) and remained significantly associated with high GM-CSF Ab in a multivariate logistic model, which included age, gender, small bowel location, and duration of disease. Stricturing prevalence on CTE or MRE examination increased from 4% in CD patients with low GM-CSF Ab to 19% in those with high GM-CSF Ab (P = 0.03).
  
  
  CONCLUSIONS
  Pediatric CD patients with high GM-CSF Ab levels have a higher prevalence of LN on CTE or MRE. Further study will be needed to determine whether medical therapy will reduce progression to stricturing behavior in these patients.
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. Dana.Dykes@cchmc.org
authors.forename: Dana M H
authors.initials: DM
authors.lastname: Dykes
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Towbin
authors.forename: Erin
authors.initials: E
authors.lastname: Bonkowski
authors.forename: Claudia
authors.initials: C
authors.lastname: Chalk
authors.forename: Ramona
authors.initials: R
authors.lastname: Bezold
authors.forename: Kathleen
authors.initials: K
authors.lastname: Lake
authors.forename: Mi-Ok
authors.initials: MO
authors.lastname: Kim
authors.forename: James E
authors.initials: JE
authors.lastname: Heubi
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Trapnell
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Podberesky
authors.forename: Lee A
authors.initials: LA
authors.lastname: Denson
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003251:Constriction, Pathologic / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D003424:Crohn Disease / Q000150:complications*; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D007410:Intestinal Diseases / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D008279:Magnetic Resonance Imaging; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D014057:Tomography, X-Ray Computed
chemical_list: D001323:Autoantibodies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
references.citation: Inflamm Bowel Dis. 2012 Feb;18(2):219-25
references.pmid: 21337477
references.citation: Gastroenterology. 2008 Oct;135(4):1114-22
references.pmid: 18725221
references.citation: Inflamm Bowel Dis. 2011 Dec;17(12):2488-96
references.pmid: 21391291
references.citation: World J Gastroenterol. 2009 Jul 21;15(27):3367-75
references.pmid: 19610137
references.citation: Am J Gastroenterol. 2006 Mar;101(3):645-52
references.pmid: 16464223
references.citation: Gastroenterology. 2008 Oct;135(4):1106-13
references.pmid: 18692056
references.citation: Dis Colon Rectum. 2007 Nov;50(11):1761-9
references.pmid: 17701255
references.citation: Arch Surg. 2010 May;145(5):471-5
references.pmid: 20479346
references.citation: Blood. 1998 Mar 15;91(6):2054-61
references.pmid: 9490690
references.citation: Br J Radiol. 2012 Jul;85(1015):876-86
references.pmid: 22553291
references.citation: Inflamm Bowel Dis. 2012 May;18(5):849-56
references.pmid: 21710535
references.citation: Inflamm Bowel Dis. 2011 May;17(5):1081-8
references.pmid: 21484959
references.citation: J Pediatr Gastroenterol Nutr. 2010 Jan;50(1):27-31
references.pmid: 19934770
references.citation: Clin Gastroenterol Hepatol. 2010 Sep;8(9):789-94
references.pmid: 20566311
references.citation: J Pediatr. 2005 Jan;146(1):35-40
references.pmid: 15644819
references.citation: Inflamm Bowel Dis. 2011 Jan;17(1):112-7
references.pmid: 20812330
references.citation: Inflamm Bowel Dis. 2007 Mar;13(3):262-8
references.pmid: 17206719
references.citation: Inflamm Bowel Dis. 2011 Jun;17(6):1314-21
references.pmid: 21560194
references.citation: J Pediatr Gastroenterol Nutr. 2010 Nov;51(5):603-9
references.pmid: 20890223
references.citation: Radiology. 2009 Jun;251(3):751-61
references.pmid: 19276325
references.citation: J Clin Imaging Sci. 2011;1:35
references.pmid: 21966632
references.citation: Inflamm Bowel Dis. 2011 Jan;17(1):30-8
references.pmid: 20812335
references.citation: Acad Radiol. 2012 Jul;19(7):819-26
references.pmid: 22520509
references.citation: Gastroenterology. 2009 Apr;136(4):1261-71, e1-3
references.pmid: 19230854
references.citation: N Engl J Med. 2007 Feb 8;356(6):567-79
references.pmid: 17287477
references.citation: Inflamm Bowel Dis. 2009 May;15(5):714-9
references.pmid: 19107777
references.citation: J Pediatr Gastroenterol Nutr. 2011 May;52(5):542-8
references.pmid: 21502824
references.citation: Gastroenterology. 1996 Sep;111(3):580-6
references.pmid: 8780560
references.citation: AJR Am J Roentgenol. 2009 Jul;193(1):113-21
references.pmid: 19542402
references.citation: Gastrointest Endosc. 2008 Aug;68(2):255-66
references.pmid: 18513722
references.citation: Inflamm Bowel Dis. 2008 Dec;14(12):1701-6
references.pmid: 18623171
references.citation: Eur Radiol. 2009 Jun;19(6):1450-60
references.pmid: 19189109
references.citation: Gastroenterology. 2007 Aug;133(2):423-32
references.pmid: 17681163
references.citation: Inflamm Bowel Dis. 2011 Aug;17(8):1759-68
references.pmid: 21744431
references.citation: Blood. 2009 Mar 12;113(11):2547-56
references.pmid: 19282464
references.citation: Gut. 2009 Aug;58(8):1113-20
references.pmid: 19136510