title: Prospective assessment of antidonor cellular alloreactivity is a tool for guidance of immunosuppression in kidney transplantation.
abstract: Current characterization of the immune risk in renal transplant patients is only focused on the assessment of preformed circulating alloantibodies; however, alloreactive memory T cells are key players in mediating allograft rejection. Immune monitoring of antidonor alloreactive memory/effector T cells using an IFN-γ Elispot has been shown to distinguish patients at risk for immune-mediated graft dysfunction, suggesting a potential tool for immunosuppression individualization. In this nonrandomized study, we prospectively assessed donor and nondonor T-cell alloreactivity in 60 highly alloreactive patients receiving calcineurin inhibitor-based immunosuppression and in non-T-cell alloreactive transplant recipients treated with a calcineurin inhibitor-free regimen. The impact was evaluated using 1-year allograft outcome. We found a strong association between ongoing antidonor T-cell alloreactivity and histological lesions of acute T cell-mediated rejection in 6-month protocol biopsies, distinguishing those patients with better 1-year graft function, regardless of immunosuppression regimen. Interestingly, evidence for enhanced immune regulation, driven by circulating Foxp3-demethylated regulatory T cells, was only observed among patients achieving antidonor T-cell hyporesponsiveness. Thus, prospective evaluation of donor-specific T-cell sensitization may add crucial information on the alloimmune state of transplanted patients to be used in daily clinical practice.
authors.affiliation: 1] Renal Transplant Unit, Nephrology Department, Bellvitge University Hospital, Barcelona, Spain [2] Experimental Nephrology Department, IDIBELL, Barcelona University, Barcelona, Spain.
authors.forename: Oriol
authors.initials: O
authors.lastname: Bestard
authors.forename: Josep M
authors.initials: JM
authors.lastname: Cruzado
authors.forename: Marc
authors.initials: M
authors.lastname: Lucia
authors.forename: Elena
authors.initials: E
authors.lastname: Crespo
authors.forename: Linda
authors.initials: L
authors.lastname: Casis
authors.forename: Birgit
authors.initials: B
authors.lastname: Sawitzki
authors.forename: Katrin
authors.initials: K
authors.lastname: Vogt
authors.forename: Carme
authors.initials: C
authors.lastname: Cantarell
authors.forename: Joan
authors.initials: J
authors.lastname: Torras
authors.forename: Edoardo
authors.initials: E
authors.lastname: Melilli
authors.forename: Richard
authors.initials: R
authors.lastname: Mast
authors.forename: Alberto
authors.initials: A
authors.lastname: Martinez-Castelao
authors.forename: Montse
authors.initials: M
authors.lastname: Gomà
authors.forename: Petra
authors.initials: P
authors.lastname: Reinke
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Josep M
authors.initials: JM
authors.lastname: Grinyó
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D019175:DNA Methylation; D004359:Drug Therapy, Combination; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D006084:Graft Rejection / Q000175:diagnosis / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007156:Immunologic Memory / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000378:metabolism; D059425:Interferon-gamma Release Tests; D007519:Isoantigens / Q000276:immunology*; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C573415:IFNG protein, human; D007166:Immunosuppressive Agents; D007519:Isoantigens; D007371:Interferon-gamma