The Blood Levels of the Amino Acid Kynurenine and Indoloxigenase are Predictive of Acute Graft Versus Host Disease (aGVHD)

Abstract

The main barrier to the success of hematopoietic stem cell transplantation (HSCT) is acute graft versus host disease (aGVHD). The risk factors for aGVHD are mainly clinical and can be improved if additional biological factors are incorporated, such as the metabolomic profile. It is known that the levels of various metabolites measured are important in the process of immunoregulation [1]. In our population study we investigated the systemic metabolic profile for 26 (Group I) allotransplant recipients. The metabolomics study was carried out by Targeted Mass Spectrometry. Plasma samples of the 26 patients were collected before the Conditioning Regimen of HSCT. All patients were clinically evaluated until 2 years after transplant and then Group I was subdivided into subgroup IA: 16 patients that presented aGVHD and subgroup IB: 10 patients without aGVHD. When comparing the metabolites dosages from subgroup IA with those of subgroup IB, it was observed that 25 metabolites We then verified by bioinformatics analyses that the ratio Kynurenine/Tryptophan which estimates the Indoloxigenase (IDO) enzyme activity. Kynurenine and the IDO enzyme are metabolites that present clinical evidence in the literature regarding the immunotolerance process. The role of IDO enzyme in the maintenance of the allogeneic fetus in pregnant women was verified in an animal model in 1998 by Mellor and Munn. Thus, the pre-transplant analysis of the metabolomics profile of allotransplant recipients seems to contribute to a better understanding of immunological process and lower dosages of Kynurenine and IDO activity enzyme pre-transplant can identify patients at higher risk for developing aGVHD. RESEaRCh aRTICLE