title: Pre-transplant donor-specific T-cell alloreactivity is strongly associated with early acute cellular rejection in kidney transplant recipients not receiving T-cell depleting induction therapy.
abstract: Preformed T-cell immune-sensitization should most likely impact allograft outcome during the initial period after kidney transplantation, since donor-specific memory T-cells may rapidly recognize alloantigens and activate the effector immune response, which leads to allograft rejection. However, the precise time-frame in which acute rejection is fundamentally triggered by preformed donor-specific memory T cells rather than by de novo activated naïve T cells is still to be established. Here, preformed donor-specific alloreactive T-cell responses were evaluated using the IFN-γ ELISPOT assay in a large consecutive cohort of kidney transplant patients (n = 90), to assess the main clinical variables associated with cellular sensitization and its predominant time-frame impact on allograft outcome, and was further validated in an independent new set of kidney transplant recipients (n = 67). We found that most highly T-cell sensitized patients were elderly patients with particularly poor HLA class-I matching, without any clinically recognizable sensitizing events. While one-year incidence of all types of biopsy-proven acute rejection did not differ between T-cell alloreactive and non-alloreactive patients, Receiver Operating Characteristic curve analysis indicated the first two months after transplantation as the highest risk time period for acute cellular rejection associated with baseline T-cell sensitization. This effect was particularly evident in young and highly alloreactive individuals that did not receive T-cell depletion immunosuppression. Multivariate analysis confirmed preformed T-cell sensitization as an independent predictor of early acute cellular rejection. In summary, monitoring anti-donor T-cell sensitization before transplantation may help to identify patients at increased risk of acute cellular rejection, particularly in the early phases after kidney transplantation, and thus guide decision-making regarding the use of induction therapy.
authors.affiliation: Experimental Nephrology Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Crespo
authors.affiliation: Experimental Nephrology Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Lucia
authors.affiliation: Experimental Nephrology Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain; Renal Transplant Unit, Nephrology department, Bellvitge University Hospital, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Cruzado
authors.affiliation: Experimental Nephrology Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Luque
authors.affiliation: Renal Transplant Unit, Nephrology department, Bellvitge University Hospital, Barcelona, Spain.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Melilli
authors.affiliation: Experimental Nephrology Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain; Renal Transplant Unit, Nephrology department, Bellvitge University Hospital, Barcelona, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Manonelles
authors.affiliation: Experimental Nephrology Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Lloberas
authors.affiliation: Experimental Nephrology Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain; Renal Transplant Unit, Nephrology department, Bellvitge University Hospital, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Torras
authors.affiliation: Experimental Nephrology Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain; Renal Transplant Unit, Nephrology department, Bellvitge University Hospital, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Grinyó
authors.affiliation: Experimental Nephrology Laboratory, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain; Renal Transplant Unit, Nephrology department, Bellvitge University Hospital, Barcelona, Spain.
authors.forename: Oriol
authors.initials: O
authors.lastname: Bestard
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D007166:Immunosuppressive Agents