title: Granulocyte macrophage colony-stimulating factor auto-antibodies and disease relapse in inflammatory bowel disease.
abstract: OBJECTIVE
  Along with others, we have reported that neutralization of granulocyte macrophage colony-stimulating factor (GM-CSF) increases intestinal permeability and bacterial translocation, and reduces neutrophil bacterial killing and anti-microbial seroreactivity. The objective was to investigate the utility of serum GM-CSF auto-antibody (Ab) as a marker for confirmation of stable remission and prediction of relapses in patients with inflammatory bowel disease (IBD).
  
  
  METHODS
  We consecutively included 181 adults and children with Crohn's disease (CD, n=61) or ulcerative colitis (UC, n=120). Over a 3-year period, we collected 861 serum samples and 610 stool samples during regular follow-up visits. GM-CSF Abs and fecal S100 proteins were measured by an enzyme-linked immunoassay.
  
  
  RESULTS
  Serum GM-CSF Ab levels correlated with disease activity, location, and extent. Time course analysis before and after relapse showed a clear increase of GM-CSF Ab concentrations up to 6 months before clinical relapse. At 1.7 μg/ml (CD) and 0.5 μg/ml (UC), the sensitivity and specificity of GM-CSF Ab for predicting relapse already 2-6 months earlier were 88% and 95% in CD and 62% and 68% in UC, respectively. A baseline GM-CSF Ab level of >1.7 μg/ml was significantly associated with relapse of CD within 18 months.
  
  
  CONCLUSIONS
  As GM-CSF is required for myeloid cell antimicrobial functions and homeostatic responses to tissue injury, serum GM-CSF Ab levels might reflect the degree of bowel permeability and bacterial translocation. Therefore, GM-CSF Ab might identify IBD patients at risk of disease relapse at an early stage, which makes the test a potential tool for monitoring disease activity and optimizing therapy.
authors.affiliation: 1] Department of Pediatric Rheumatology and Immunology, University Children's Hospital Münster, Münster, Germany [2] Interdisciplinary Center of Clinical Research, University of Münster, Münster, Germany [3] The Royal Children's Hospital Melbourne, Murdoch Children's Research Institute, Parkville, Victoria, Australia [4] Department of Pediatrics, University of Melbourne, Melboure Medical School, Parkville, Victoria, Australia.
authors.forename: Jan
authors.initials: J
authors.lastname: Däbritz
authors.forename: Erin
authors.initials: E
authors.lastname: Bonkowski
authors.forename: Claudia
authors.initials: C
authors.lastname: Chalk
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Trapnell
authors.forename: Jost
authors.initials: J
authors.lastname: Langhorst
authors.forename: Lee A
authors.initials: LA
authors.lastname: Denson
authors.forename: Dirk
authors.initials: D
authors.lastname: Foell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000737:chemistry; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D012680:Sensitivity and Specificity
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D016178:Granulocyte-Macrophage Colony-Stimulating Factor