A comprehensive assessment of long-term SARS-CoV-2-specific adaptive immune memory in convalescent COVID-19 Solid Organ Transplant recipients.

Long-term adaptive immune memory has been reported among immunocompetent individuals up to eight months following SARS-CoV-2 infection. However, limited data is available in convalescent patients with a solid organ transplant. To investigate this, we performed a thorough evaluation of adaptive immune memory at different compartments (serological, memory B cells and cytokine [IFN-γ, IL-2, IFN-γ/IL12 and IL-21] producing T cells) specific to SARS-CoV-2 by ELISA and FluoroSpot-based assays in 102 convalescent patients (53 with a solid organ transplants (38 kidney, 5 liver, 5 lung and 5 heart transplant) and 49 immunocompetent controls) with different clinical COVID-19 severity (severe, mild and asymptomatic) beyond six months after infection. While similar detectable memory responses at different immune compartments were detected between those with a solid organ transplant and immunocompetent individuals, these responses were predominantly driven by distinct COVID-19 clinical severities (97.6%, 80.5% and 42.1%, all significantly different, were seropositive; 84% vs 75% vs 35.7%, all significantly different, showed IgG-producing memory B cells and 82.5%, 86.9% and 31.6%, displayed IFN-γ producing T cells; in severe, mild and asymptomatic convalescent patients, respectively). Notably, patients with a solid organ transplant with longer time after transplantation did more likely show detectable long-lasting immune memory, regardless of COVID-19 severity. Thus, our study shows that patients with a solid organ transplant are capable of maintaining long-lasting peripheral immune memory after COVID-19 infection; mainly determined by the degree of infection severity.

De novo use of a generic formulation of tacrolimus versus reference tacrolimus in kidney transplantation: evaluation of the clinical results, histology in protocol biopsies, and immunological monitoring.

The use of generic formulations of immunosuppressive drugs in renal transplantation has been and still is a controversial subject. The lack of clinical studies about safety and efficacy in transplant patients is one of the factors restricting the diffusion of generic drugs in the renal transplant field. Since March 2013, our transplant unit has incorporated generic tacrolimus (Adoport(®) ; Sandoz), replacing the one we were currently using (Prograf(®) ; Astellas). When carrying out our retrospective analysis comparing the two different formulations, we evaluated several clinical results: tacrolimus trough concentrations (C0) at 5-7 days; 1, 3, and 6 months post-transplantation; concentration/dose ratio at 6 months; acute rejection incidence; delayed graft function (DGF); renal function (as CKD-EPI); and proteinuria at 6 months in 120 patients (1:1 ratio of Prograf(®) versus Adoport(®) ), noticing no important differences. We also evaluated the results of protocol biopsies at 6 months in a subgroup of patients, thus verifying the safety and efficacy of this particular generic drug versus the reference product on a histological basis as well. No difference in the development of dnDSA (de novo donor-specific antibody) was found between the two groups.

Prospective assessment of antidonor cellular alloreactivity is a tool for guidance of immunosuppression in kidney transplantation.

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.