title: Serum analysis of tryptophan catabolism pathway: correlation with Crohn's disease activity.
abstract: BACKGROUND
  Indoleamine 2,3 dioxygenase-1 (IDO1) is a tryptophan catabolizing enzyme with immunotolerance-promoting functions. We sought to determine if increased gut expression of IDO1 in Crohn's disease (CD) would result in detectable changes in serum levels of tryptophan and the initial IDO1 pathway catabolite, kynurenine.
  
  
  METHODS
  Individuals were prospectively enrolled through the Washington University Digestive Diseases Research Center. The Montreal Classification was used for disease phenotyping. Disease severity was categorized by the Physician's Global Assessment. Serum tryptophan and kynurenine were measured by high-pressure liquid chromatography. IDO1 immunohistochemical staining was performed on formalin-fixed tissue blocks.
  
  
  RESULTS
  In all, 25 CD patients and 11 controls were enrolled. Eight CD patients had serum collected at two different timepoints and levels of disease activity compared. Strong IDO1 expression exists in both the lamina propria and epithelium during active CD compared to controls. Suppressed serum tryptophan levels and an elevated kynurenine/tryptophan (K/T) ratio were found in individuals with active CD as compared to those in remission or the control population. K/T ratios correlated positively with disease activity as well as with C-reactive protein and erythrocyte sedimentation rate. In the subgroup of CD patients with two serum measurements, tryptophan levels were elevated while kynurenine levels and the K/T ratio lowered as the disease activity lessened.
  
  
  CONCLUSIONS
  IDO1 expression in CD is associated with lower serum tryptophan and an elevated K/T ratio. These levels may serve as a reasonable objective marker of gut mucosal immune activation and as a surrogate for CD activity.
authors.affiliation: Division of Gastroenterology, Washington University in Saint Louis School of Medicine, St. Louis, Missouri, USA.
authors.forename: Nitin K
authors.initials: NK
authors.lastname: Gupta
authors.forename: Ameet I
authors.initials: AI
authors.lastname: Thaker
authors.forename: Navya
authors.initials: N
authors.lastname: Kanuri
authors.forename: Terrence E
authors.initials: TE
authors.lastname: Riehl
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Rowley
authors.forename: William F
authors.initials: WF
authors.lastname: Stenson
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Ciorba
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D003424:Crohn Disease / Q000097:blood* / Q000175:diagnosis / Q000201:enzymology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007737:Kynurenine / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D014364:Tryptophan / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan