Serum analysis of tryptophan catabolism pathway: correlation with Crohn's disease activity.

Serum analysis of tryptophan catabolism pathway: correlation with Crohn's disease activity.
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DOI:
10.1002/ibd.21849
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发表时间:
2012-07
影响因子:
4.9
通讯作者:
Ciorba, Matthew A.
Ciorba, Matthew A.
中科院分区:
医学2区
文献类型:
--
作者:
Gupta, Nitin K.;Thaker, Ameet I.;Kanuri, Navya;Riehl, Terrence E.;Rowley, Christopher W.;Stenson, William F.;Ciorba, Matthew A.

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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. Individuals were prospectively enrolled through the Washington University Digestive Diseases Research Center. Montreal classification was used for disease phenotyping. Disease severity was categorized by 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. 25 CD patients and 11 controls were enrolled. 8 CD patients had serum collected at two different time points and levels of disease activity. 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 elevated while kynurenine levels and the K/T ratio lowered as the disease activity lessened. IDO1 expression in Crohn’s disease is associated with lower serum tryptophan and an elevated K/T ratio. These levels may serve a reasonable objective marker of gut mucosal immune activation and surrogate for Crohn’s Disease activity.
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