Operational tolerance is an alternative to lifelong immunosuppression after transplantation. One strategy to achieve tolerance is by T regulatory cells. Safety and feasibility of a T regulatory type 1 (Tr1)-cell—based therapy to prevent graft versus host disease in patients with hematological malignancies has been already proven. We are now planning to perform a Tr1-cell—based therapy after kidney transplantation. Upon tailoring the lab-grade protocol to patients on dialysis, aims of the current work were to develop a clinical-grade compatible protocol to generate a donor-specific Tr1-cell—enriched medicinal product (named T10 cells) and to test the Tr1-cell sensitivity to standard immunosuppression in vivo to define the best timing of cell infusion. We developed a medicinal product that was enriched in Tr1 cells, anergic to donor-cell stimulation, able to suppress proliferation upon donor- but not third-party stimulation in vitro, and stable upon cryopreservation. The protocol was reproducible upon up scaling to leukapheresis from patients on dialysis and was effective in yielding the expected number of T10 cells necessary for the planned infusions. The tolerogenic gene signature of circulating Tr1 cells was minimally compromised in kidney transplant recipients under standard immunosuppression and it eventually started to recover 36 weeks post-transplantation, providing rationale for selecting the timings of the cell infusions. These data provide solid ground for proceeding with the trial and establish robust rationale for defining the correct timing of cell infusion during concomitant immunosuppressive treatment.

Background: Obesity may negatively impact clinical outcomes in kidney transplant (KT) recipients. Limited information is available on the prevalence of obesity in this population, and on the lifestyle habits associated with obesity. Methods: we conducted an online, anonymous survey to assess of the proportion of KT recipients with obesity, adherence to the Mediterranean diet (i.e., a dietary regimen with proven renal and cardiovascular outcomes) using the MEDI-Lite questionnaire, and level of physical activity using the International Physical Activity Questionnaire (IPAQ) short form among KT recipients. Results: 255 KT recipients participated. Median (25th–75th quartile) age was 56.0 (48.0; 62.0) years, 43.9% female, median BMI 23.9 (21.6; 26.5) kg/m². The proportion of KT recipients with obesity was 9.8% (95% confidence interval, 6.4 to 14.1%). Adequate adherence to the Mediterranean diet (Medi-Lite score >9) was overall low (44.7%; 40.0 vs. 45.2% in those with or without obesity, respectively; p = 0.618). In participants with obesity the Medi-Lite score inversely correlated with BMI (R = −0.45; p < 0.025). Overall, 30.6% of participants had a low level of physical activity (44.0 vs. 29.1% of those with or without obesity, respectively; p = 0.125). The amount of energy expended walking was significantly lower among participants with obesity (462 (0.0; 1436) vs. 1056 (433; 2005) METs/week, p = 0.017). Conclusions: the burden of obesity among KT recipients is similar to that of the general population. Adherence to the Mediterranean diet was generally low, and nearly one-third of participants had a low level of physical activity. Building specialized multidisciplinary teams to manage obesity in KT recipients is urgently needed.

Background: Solid organ transplant (SOT) recipients may be at increased risk for severe disease and mortality from COVID-19 because of immunosuppression and prolonged end-stage organ disease. As a transplant center serving a diverse patient population, we report the cumulative incidence and outcomes of SARS-CoV-2 infection in our cohort of SOT recipients. Methods: We prospectively included in this observational study SOT recipients with a functioning kidney (n = 201), pancreas ± kidney (n = 66) or islet transplant (n = 24), attending outpatient regular follow-up at the San Raffaele Hospital from February 2020 to April 2021. Antibodies to SARS-CoV-2 were tested in all patients by a luciferase immunoprecipitation system assay. Results: Of the 291 SOT recipients, 30 (10.3%) tested positive for SARS-CoV-2 during the study period and prevalence was not different among different transplants. The SARS-CoV-2 antibody frequency was around 2.6-fold higher than the incidence of cases who tested positive for SARS-CoV-2 RT-PCR. As for the WHO COVID-19 severity classification, 19 (63.3%) SOT recipients were mild, nine (30%) were moderate, and two were critical and died yielding a crude mortality rate in our patient population of 6.7%. Kidney transplant (OR 12.9 (1.1–150) p = 0.041) was associated with an increased risk for moderate/critical disease, while statin therapy (OR 0.116 (0.015–0.926) p = 0.042) and pancreas/islet transplant (OR 0.077 (0.007–0.906) p = 0.041) were protective. Conclusions: The incidence of SARS-CoV-2 infection in SOT recipients may be higher than previously described. Due to the relative high crude mortality, symptomatic SOT recipients must be considered at high risk in case of SARS-CoV-2 infection.