title: Increased suppressor of cytokine signaling-3 expression predicts mucosal relapse in ulcerative colitis.
abstract: BACKGROUND
  Most biomarkers predicting mucosal relapse of ulcerative colitis (UC) patients in clinical remission represent low levels of mucosal inflammation. Since SOCS3 expression may increase the vulnerability of intestinal epithelial cells (IECs) to various insults, we investigated whether its expression predicts mucosal relapse in UC patients in clinical remission without any signs of mucosal inflammation.
  
  
  METHODS
  UC patients (n = 32) in clinical, endoscopic, and histological remission were followed up for 9 years. IEC expression of SOCS3, p-STAT3, and p-STAT1 were assessed with biopsies from the baseline colonoscopy, last colonoscopy before relapse, and colonoscopy at relapse. Clinical data, endoscopy, and histology reports were collected from patient charts.
  
  
  RESULTS
  Twenty-six (81%) patients had histological relapse, 19 (59%) developed an endoscopic relapse, and 17 (53%) had a clinical relapse during follow-up. SOCS3 expression at first colonoscopy during remission correlated with shorter time to histological, endoscopic, and clinical relapse. SOCS3 expression was increased at the last colonoscopy before relapse, approaching relapse levels, whereas p-STAT3 expression was low during the entire remission. A positive correlation between IEC SOCS3 and its inducer p-STAT1 was shown.
  
  
  CONCLUSIONS
  SOCS3 IEC expression during remission may be useful in predicting mucosal relapse in patients without any signs of mucosal inflammation. These data strengthen our hypothesis that SOCS3 contributes to enhanced vulnerability of IEC during remission. Thus, SOCS3 levels during remission may function as a therapeutic target for clinical monitoring and early induction of mucosal healing.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, Netherlands.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Veerle J A A
authors.initials: VJ
authors.lastname: Nuij
authors.forename: Judith E
authors.initials: JE
authors.lastname: Baars
authors.forename: Katharina
authors.initials: K
authors.lastname: Biermann
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Kuipers
authors.forename: Maikel P
authors.initials: MP
authors.lastname: Peppelenbosch
authors.forename: Colin
authors.initials: C
authors.lastname: de Haar
authors.forename: C
authors.initials: C
authors.lastname: Janneke van der Woude
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D003093:Colitis, Ulcerative / Q000150:complications* / Q000378:metabolism / Q000628:therapy; D003113:Colonoscopy; D016099:Endoscopy, Gastrointestinal; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D010766:Phosphorylation; D011379:Prognosis; D012008:Recurrence; D012074:Remission Induction; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C106644:SOCS3 protein, human; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins