title: Candidate Serum Markers in Early Crohn's Disease: Predictors of Disease Course.
abstract: OBJECTIVE
  More than half of patients with Crohn's disease [CD] develop disease complications requiring aggressive medical therapy or surgery over time. However, predicting disease course and treatment response remains difficult. We therefore identified distinctive serum analytes associated with disease activity and course in newly diagnosed, untreated patients at presentation and during their follow-up.
  
  
  METHODS
  In a pilot study, a multiplex immunoassay analysis on 36 markers was performed on serum from 20 CD patients at the time of primary diagnosis following endoscopic evaluation. The 12 most potent markers associated with disease activity, phenotype and course were analysed in a consecutive cohort of 66 CD patients at diagnosis and follow-up [n = 39]. A healthy control group [n = 20] was included as a reference.
  
  
  RESULTS
  CD patients had higher baseline levels of sTNF-R2 [p = 0.001], sIL-2R [p = 0.0001], and MMP-1 [p = 0.001] compared with healthy controls. Serial measurements revealed that these three analytes dropped statistically significantly from baseline level during remission and were high during exacerbation. Great decline of sTNF-R1 levels was found during remission, with 6.7-fold lower levels than in healthy controls [p = 0.015]. Patients who did not respond to initial prednisone treatment had higher baseline levels of sTNF-R2 [p = 0.001]. Patients experiencing relapses during follow-up had lower baseline sTNF-R2 and VCAM levels compared with patients with long-lasting remission.
  
  
  CONCLUSIONS
  In a large cohort of newly diagnosed untreated CD patients, we identified candidate serum markers [sTNF-R1, sTNF-R2, sIL-2R, and MMP-1] associated with disease activity. Furthermore, sTNF-R2 was associated with prednisone response and, together with VCAM, with long-lasting remission.
authors.affiliation: Crohn & Colitis Centre Rijnstate, Rijnstate Hospital, Arnhem, The Netherlands.
authors.forename: Carolijn
authors.initials: C
authors.lastname: Smids
authors.affiliation: Crohn & Colitis Centre Rijnstate, Rijnstate Hospital, Arnhem, The Netherlands.
authors.forename: Carmen S
authors.initials: CS
authors.lastname: Horjus Talabur Horje
authors.affiliation: U-DAIR and Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Nierkens
authors.affiliation: Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Julia
authors.initials: J
authors.lastname: Drylewicz
authors.affiliation: Crohn & Colitis Centre Rijnstate, Rijnstate Hospital, Arnhem, The Netherlands.
authors.forename: Marcel J M
authors.initials: MJM
authors.lastname: Groenen
authors.affiliation: Crohn & Colitis Centre Rijnstate, Rijnstate Hospital, Arnhem, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wahab
authors.affiliation: Department of Microbiology and Immunology, Rijnstate Hospital, Arnhem, The Netherlands.
authors.forename: Ellen G
authors.initials: EG
authors.lastname: van Lochem
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D003424:Crohn Disease / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007118:Immunoassay; D060828:Induction Chemotherapy; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D010865:Pilot Projects; D011241:Prednisone / Q000627:therapeutic use; D012008:Recurrence; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D011241:Prednisone
keywords: Crohn’s Disease; analytes; markers; multiplex; soluble receptors; untreated