Landfried, Karin and Zhu, Wentao and Waldhier, Magdalena C. and Schulz, Ute and Ammer, Julia and Holler, Barbara and Wolff, Daniel and Edinger, Matthias and Peter, Katrin and Kreutz, Marina and Andreesen, Reinhard and Oefner, Peter J. and Holler, Ernst (2011) Tryptophan catabolism is associated with acute GVHD after human allogeneic stem cell transplantation and indicates activation of indoleamine 2,3-dioxygenase. BLOOD, 118 (26). pp. 6971-6974. ISSN 0006-4971, 1528-0020
Full text not available from this repository. (Request a copy)Abstract
Induction of indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme in tryptophan degradation along the kynurenine pathway, acts as a potent immunoregulatory loop. To address its role in human allogeneic stem cell transplantation, we measured major tryptophan metabolites, such as quinolinic acid and kynurenine, in serial urine specimens from 51 patients by liquid chromatography-tandem mass spectrometry. Samples were collected between admission and day 90 after transplantation, and metabolite levels were correlated with early clinical events and outcome. In selected patients, IDO gene expression was assessed by quantitative RT-PCR in intestinal biopsies. Surviving patients had significantly lower metabolite levels on days 28, 42, and 90, respectively, compared with patients dying of GVHD and associated complications (n = 10). Kynurenine levels were directly correlated with severity and clinical course of GVHD: Mean urinary quinolinic acid levels were 4.5 +/- 0.3 mu mol/mmol creatinine in the absence of acute GVHD, 8.0 +/- 1.1 mu mol/mmol creatinine for GVHD grade 1 or 2, and 13.5 +/- 2.7 mu mol/mmol creatinine for GVHD grade 3 or 4 (P < .001), respectively. GVHD-dependent induction of IDO was further suggested by increased expression of IDO mRNA in intestinal biopsies from patients with severe GVHD. Our data indicate reactive release of kynurenines in GVHD-associated inflammation. (Blood. 2011;118(26):6971-6974)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | KIDNEY ALLOGRAFT-REJECTION; VERSUS-HOST-DISEASE; ANTITHYMOCYTE GLOBULIN; IMMUNE TOLERANCE; INDUCTION; EXPRESSION; IDO; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 May 2020 05:07 |
| Last Modified: | 26 May 2020 05:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19669 |
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