Increased Plasma Indoleamine 2,3-Dioxygenase Activity Correlates with the Severity of Acute Graft-Versus-Host Disease

Abstract 1985

Indoleamine 2,3-dioxygenase (IDO) is a rate-limiting enzyme for the tryptophan catabolism, which plays an important role in the induction of immune tolerance. To evaluate the expression level of IDO in the patients receiving hematopoietic stem cell transplantation (HSCT) and to identify the possible correlation between IDO activity and acute graft-versus-host disease (aGVHD), we collected blood samples from 96 patients before and after HSCT and 10 healthy volunteers served as controls. The expression of IDO mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) in peripheral blood mononuclear cells of the patients and healthy controls. Reverse-phase high-performance liquid chromatography (HPLC) was performed to analyze the level of kynurenine (Kyn) and tryptophan (Trp) in plasma. The IDO activity was calculated as the ratio of kyn to trp. Plasma IFNgama was measured by standard ELISA. RT-PCR showed that IDO mRNA was detected in 65 of 85(65/85, 76.5%) patients with aGVHD; in patients without aGVHD, only 1 of them express IDO mRNA (1/11, 9.1%); none of 10 healthy volunteers was positive for the IDO expression. The plasma IDO activity was much higher in aGVHD group than those without aGVHD(4.49¡À0.46 vs. 1.69¡À0.9, respectively; p < 0.0001) or the healthy controls(4.49¡À0.46 vs. 1.77¡À0.22, respectively; p < 0.0001). Patients with severe aGVHD (grade III/IV) had significantly higher IDO activity than those with mild aGVHD (grade I/II) (6.74¡À0.58 vs. 2.17¡À0.79, respectively; p < 0.0001). IDO activity was decreased following effective treatment of aGVHD, while fluctuation of plasma IDO was also observed upon the recurrence of aGVHD. The plasma IDO activity was correlated with the IFNgama level(r=0.8816).