Table 1.
Patients’ demographic characteristics.
Fig 1.
Pre-transplant d-s T-cell alloreactivity positively correlates with recipient age and with HLA class I mismatch.
A. Correlation between pre-transplant frequency of donor-specific IFN-γ T-cell spots and recipient age (years) (R = 0.349, p = 0.001). B. Correlation between pre-transplant frequency of donor-specific IFN-γ T-cell spots and class I HLA mismatches (R = 0.207, p = 0.05).
Table 2.
Impact of pre-transplant d-s T-cell allosensitization on allograft outcome.
Fig 2.
Pre-transplant d-s T-cell alloreactivity and early TCMR.
No differences between preformed donor-specific T-cell alloreactive responses and incidence of all types of BPAR were observed. Nevertheless, kidney transplant patients developing early TCMR (< 2 months after transplantation) showed significantly higher preformed donor-specific T-cell sensitization than those that did not (10/37;27% vs 5/53;9.4%, p = 0.028). Red dots represent pre-transplant T-cell alloreactive kidney transplant patients developing early TCMR.
Fig 3.
Receiver operating characteristic (ROC) curve estimating the most likely time-frame of TCMR associated with pre-transplant T-cell sensitization.
Positive pre-transplant T-cell sensitization was a highly sensitive and specific predictor of the advent of TCMR during the first 8 weeks (1.65 months) after transplantation (AUC = 0.701; p = 0.065).
Fig 4.
Incidence of early TCMR is higher within young T-cell alloreactive transplant recipients than in elderly patients.
Pre-transplant T-cell alloreactive individuals younger than 50 years old (R<50/ELISPOT+) showed significantly higher incidence of early TCMR than young patients with a negative T-cell ELISPOT (R<50/ELISPOT-) and elderly patients with either a positive (R>50/ELISPOT+) or negative pre-transplant ELISPOT (R>50/ELISPOT-), (6/15;40%, 3/15;20%, 4/15;26.7%, 2/15;13.3%, respectively, p = 0.030). Statistically significant differences were found between alloreactive individuals below 50 (R<50/ELISPOT+) and non-alloreactive patients pre-transplantation [(R<50/ELISPOT-) and (R>50/ELISPOT-)] (p = 0.012 and p = 0.014 respectively). A trend toward a significant difference was observed between patients under 50 and elderly alloreactive patients (p = 0.091).
Fig 5.
T-cell depletion induction therapy provides protection against early TCMR.
5a. Patients receiving T-cell depletion as induction therapy showed significantly lower incidence of early TCMR [3.8% (1/26) vs 22% (14/64) p = 0.038] than those that did not.5b. Incidence of early TCMR in anti-donor T-cell sensitized patients receiving either anti-IL2 receptor blockade or rATG. A higher incidence of early TCMR was observed among highly T-cell sensitized patients receiving anti-IL2 receptor blockade than in patients receiving rATG [36.4% (8/22) and 8% (1/12); p = 0.07 respectively].
Table 3.
Univariate and step-wise multivariate analyses of variables predicting early T-cell mediated rejection (TCMR).
Table 4.
Predictive value of IFN-γ ELISPOT assay for early TCMR in an independent validation cohort.