title: Elevated levels of serum-soluble triggering receptor expressed on myeloid cells-1 in patients with IBD do not correlate with intestinal TREM-1 mRNA expression and endoscopic disease activity.
abstract: OBJECTIVE
  Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory responses. We have previously demonstrated a substantial increase in TREM-1-expressing macrophages in the inflamed intestinal mucosa of patients with inflammatory bowel diseases (IBD). TREM-1 is also produced as a soluble receptor (sTREM-1). Here, we aimed to determine whether serum sTREM-1 could be used as a surrogate marker of disease activity in patients with IBD.
  
  
  METHODS
  Intestinal biopsies and concurrently collected sera from patients with Crohn's disease (CD) and Ulcerative colitis (UC) enrolled in the Swiss IBD cohort study were analyzed for intestinal TREM-1 mRNA and serum sTREM-1 expression. TREM-1 mRNA and sTREM-1 were correlated with the endoscopically determined disease activity. Serum sTREM-1 and TREM-1 mRNA expression levels were further determined in sera and colonic tissues collected at various time-points post disease induction in an experimental mouse model of colitis and correlated with disease activity.
  
  
  RESULTS
  Expression of TREM-1 mRNA was upregulated in intestinal biopsies from patients with active disease but not in patients with quiescent disease. Serum sTREM-1 was elevated in IBD patients compared to normal controls. No substantial differences in sTREM-1 expression levels were found in patients with active versus quiescent disease. In colitic mice, colonic TREM-1 mRNA and serum sTREM-1 were also upregulated. While colonic TREM-1 mRNA expression levels correlated with disease activity, augmented serum sTREM-1 in fact associated with a milder course of disease.
  
  
  CONCLUSIONS
  Analysis of sTREM-1 as a surrogate marker of disease activity in patients with IBD warrants caution.
authors.affiliation: Division of Experimental Pathology, Institute of Pathology, University of Bern, Bern, Switzerland. leslie.saurer@pathology.unibe.ch
authors.forename: Leslie
authors.initials: L
authors.lastname: Saurer
authors.forename: Silvia
authors.initials: S
authors.lastname: Rihs
authors.forename: Michèle
authors.initials: M
authors.lastname: Birrer
authors.forename: Nikolina
authors.initials: N
authors.lastname: Saxer-Seculic
authors.forename: Markus
authors.initials: M
authors.lastname: Radsak
authors.forename: Christoph
authors.initials: C
authors.lastname: Mueller
mesh_terms: D019264:Adoptive Transfer; D000328:Adult; D000818:Animals; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D003093:Colitis, Ulcerative / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D003106:Colon / Q000473:pathology; D003424:Crohn Disease / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D016099:Endoscopy, Gastrointestinal; D005260:Female; D006801:Humans; D007082:Ileum / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood* / Q000235:genetics*; D051379:Mice; D008875:Middle Aged; D012333:RNA, Messenger / Q000097:blood* / Q000378:metabolism; D012372:ROC Curve; D011971:Receptors, Immunologic / Q000097:blood* / Q000235:genetics*; D018709:Statistics, Nonparametric; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D015415:Biomarkers; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1