title: Increased plasma indoleamine 2,3-dioxygenase activity and interferon-γ levels correlate with the severity of acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
abstract: Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme for the tryptophan catabolism that plays an important role in the induction of immune tolerance. To evaluate the expression levels of IDO and interferon (IFN)-γ in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) and to identify the correlation between IDO activity, IFN-γ, and acute graft-versus-host disease (aGVHD), we measured IDO mRNA expression in peripheral blood mononuclear cells in 89 allo-HSCT patients by reverse transcription-polymerase chain reaction. The IDO activity in plasma was also performed by reverse-phase high-performance liquid chromatography; plasma IFN-γ was detected by a standard enzyme-linked immunosorbent assay. IDO mRNA was detected in 55 of 74 patients (74.32%) with aGVHD. Of patients without aGVHD, only 2 of 26 expressed IDO mRNA (7.69%); none of 8 healthy volunteers was positive for IDO expression. Plasma IDO activity was much higher in aGVHD patients than in those without aGVHD (4.74 ± 3.35 vs 1.79 ± 1.02, respectively; P < .0001) or in healthy control subjects (4.74 ± 3.35 vs 1.77 ± .22; P < .0001). Patients with severe (grade III/IV) aGVHD had much higher IDO activity than those with mild (grade I/II) aGVHD (6.57 ± 3.34 vs 2.46 ± 1.41; P < .0001). Meanwhile, there was a significant increase in plasma IFN-γ level in aGVHD patients (P = .0043). IDO activity decreased after alleviation of aGVHD, whereas fluctuation of plasma IDO was also observed upon the recurrence of aGVHD. Plasma IDO activity was correlated with the level of plasma IFN-γ (r = .8288; P < .0001). Using receiver-operating characteristic curves analysis, the sensitivity and specificity for evaluation of aGVHD were determined. The area under the curve of IDO activity was higher than that of IFN-γ (.852 vs .694) with a sensitivity and specificity for IDO of 81% and 78%, respectively, whereas the sensitivity and specificity for IFN-γ were 41% and 93%, respectively. IDO mRNA was expressed in blood mononuclear cells of patients with aGVHD. Plasma IDO activity was elevated in aGVHD patients and was correlated with the severity of aGVHD. In combination with plasma IFN-γ, IDO activity may represent a potential biomarker for the diagnosis and evaluation of aGVHD after allo-HSCT. Intervention of the IDO pathway may also represent an alternative way to overcome steroid-resistant aGVHD.
authors.affiliation: Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors.forename: Jinhuan
authors.initials: J
authors.lastname: Xu
authors.forename: Jia
authors.initials: J
authors.lastname: Wei
authors.forename: Xianmin
authors.initials: X
authors.lastname: Zhu
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Guan
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Yin
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiao
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood* / Q000201:enzymology / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000097:blood*; D007371:Interferon-gamma / Q000097:blood*; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous / Q000379:methods; D055815:Young Adult
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma