title: Defective leukocyte GM-CSF receptor (CD116) expression and function in inflammatory bowel disease.
abstract: OBJECTIVE
  Inflammatory bowel disease (IBD) refers to 2 chronic inflammatory diseases of the intestine, ie, ulcerative colitis and Crohn's disease. IBD results from environmental factors (eg, bacterial antigens) triggering a dysregulated immune response in genetically predisposed hosts. Although the basis of IBD is incompletely understood, a number of recent studies have implicated defective innate immune responses in the pathogenesis of IBD. In this regard, there is much interest in therapies that activate innate immunity (eg, recombinant granulocyte-macrophage colony-stimulating factor).
  
  
  METHODS
  In this study, we screened expression and function of circulating leukocyte granulocyte-macrophage colony-stimulating factor receptor (CD116) messenger RNA and surface protein in 52 IBD patients and 52 healthy controls.
  
  
  RESULTS
  Our results show that both granulocyte and monocyte CD116 levels, but not CD114 or interleukin-3Rα, were significantly decreased in IBD compared to control (P<.001) and disease controls (irritable bowel syndrome; P<.001; rheumatoid arthritis; P<.025). IBD-associated CD116 repression was more prominent in patients with ulcerative colitis compared to Crohn's disease (P<.05), was independent of disease activity (P>.05), and was not influenced by current medications (P>.05). Receiver operating characteristic curve analysis revealed that leukocyte CD116 expression is a sensitive (85%) and specific (92%) biomarker for IBD. Moreover, granulocyte CD116-mediated function (phosphorylation of signal transducers and activators of transcription 3) paralleled decreased expression of CD116 in IBD granulocytes compared to control (P<.001).
  
  
  CONCLUSIONS
  These studies identify defective expression and function of CD116 as a distinguishing feature of IBD and implicate an associated defect in innate immune responses toward granulocyte-macrophage colony-stimulating factor.
authors.affiliation: Mucosal Inflammation Program, Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, Colorado 80045, USA.
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Goldstein
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Kominsky
authors.forename: Nicole
authors.initials: N
authors.lastname: Jacobson
authors.forename: Brittelle
authors.initials: B
authors.lastname: Bowers
authors.forename: Kirsten
authors.initials: K
authors.lastname: Regalia
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Austin
authors.forename: Melinda
authors.initials: M
authors.lastname: Yousefi
authors.forename: Michael T
authors.initials: MT
authors.lastname: Falta
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Fontenot
authors.forename: Mark E
authors.initials: ME
authors.lastname: Gerich
authors.forename: Lucy
authors.initials: L
authors.lastname: Golden-Mason
authors.forename: Sean P
authors.initials: SP
authors.lastname: Colgan
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000097:blood / Q000235:genetics / Q000276:immunology*; D003120:Colorado; D003424:Crohn Disease / Q000097:blood / Q000235:genetics / Q000276:immunology*; D015536:Down-Regulation; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000097:blood; D012372:ROC Curve; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood* / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016178:Granulocyte-Macrophage Colony-Stimulating Factor