IRBM & Heidelberg University Hospital publishes in Cell Reports Medicine on kynurenine pathway activation and deviation to anthranilic and kynurenic acid in fibrosing chronic Graft-Versus-Host Disease

Our Biomarkers team, in collaboration with Dr. Thomas Luft group at the Heidelberg University Hospital (Germany), explored the role of tryptophan metabolites in the acute and chronic graft versus host disease (GVHD) following allogenic bone marrow transplantation. GVHD is an immune mediated disease due to complex interaction between donor (lymphoid tissue) and recipient’s immunity occurring after transplantation. Immune-competent T-cells or their precursor transplanted into immune-compromised recipients perceive the recipients as foreign and react against it. This leads to activation of T-cells ultimately causing inflammation and killing of host cells. The incidence is of 35-50% and mortality up to 75% with skin, liver and intestine being the principal target organs.

Monitoring plasma levels of Trp, KYN, KYNA, 3-HK, AA and 3OH-AA and simultaneously measuring the IDO activity and the concentration of IFNγ, CXCL9 in 425 patients with hematologic malignancies treated with bone marrow transplantation the correlation between tryptophan catabolites level and the severity of the disease were elucidated. We identified KYN pathways specifically activated in different manifestation of chronic GVHD (cGVHD, non-severe cGVHD, severe gastro-intestinal cGVHD and fibrosing cGVHD) and displayed the contribution of the IFNγ pathway. We observed an increase of CXCL9 and IDO levels and an increased IDO activity in all GVHD groups in accordance to a common IFNγ response. In addition, we identified specific kynurenine metabolism patterns for non-severe, severe fibrosing and severe gastro-intestinal cGVHD respectively, providing a molecular distinction between fibrosing and non-fibrosing cGVHD.