No augmentation of indoleamine 2,3-dioxygenase (IDO) activity through belatacept treatment in liver transplant recipients

Autor:	Alexander Kainz, Thomas Wekerle, Dietmar Fuchs, Sinda Bigenzahn, Ferdinand Muehlbacher, B Juergens, A Koenigsrainer, Gerald Brandacher, Johann Pratschke, T Becker, Benedikt Mahr
Rok vydání:	2018
Předmět:	Male 0301 basic medicine medicine.medical_treatment Immunology 030230 surgery Liver transplantation Belatacept Tacrolimus Abatacept 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Humans Indoleamine-Pyrrole 2 3 -Dioxygenase Immunology and Allergy Cytotoxic T cell Prospective Studies Indoleamine 2 3-dioxygenase Kynurenine business.industry Tryptophan CD28 Immunosuppression Original Articles Dendritic Cells Middle Aged Liver Transplantation Up-Regulation 030104 developmental biology chemistry Female business Immunosuppressive Agents medicine.drug
Zdroj:	Clinical and Experimental Immunology. 192:233-241
ISSN:	1365-2249 0009-9104
DOI:	10.1111/cei.13093
Popis:	Summary Belatacept is a second-generation cytotoxic T lymphocyte antigen (CTLA)-4 immunoglobulin (Ig) fusion protein approved for immunosuppression in renal transplant recipients. It was designed intentionally to interrupt co-stimulation via CD28 by binding to its ligands B7·1 and B7·2. Experimental evidence suggests a potential additional mechanism for CTLA-4 Ig compounds through binding to B7 molecules expressed on antigen-presenting cells (APCs) and up-regulation of indoleamine 2,3-dioxygenase (IDO), an immunomodulating enzyme that catalyzes the degradation of tryptophan to kynurenine and that down-regulates T cell immunity. So far it remains unknown whether belatacept up-regulates IDO in transplant recipients. We therefore investigated whether belatacept therapy enhances IDO activity in liver transplant recipients enrolled in a multi-centre, investigator-initiated substudy of the Phase II trial of belatacept in liver transplantation (IM103-045). Tryptophan and kynurenine serum levels were measured during the first 6 weeks post-transplant in liver transplant patients randomized to receive either belatacept or tacrolimus-based immunosuppression. There was no significant difference in IDO activity, as indicated by the kynurenine/tryptophan ratio, between belatacept and tacrolimus-treated patients in per-protocol and in intent-to-treat analyses. Moreover, no evidence was found that belatacept affects IDO in human dendritic cells (DC) in vitro. These data provide evidence that belatacept is not associated with detectable IDO induction in the clinical transplant setting compared to tacrolimus-treated patients.
Databáze:	OpenAIRE
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