Impact of T Lymphocytes Isolated from Liver Perfusate of Deceased Brain Donors on Kidney Transplantation: Preliminary Evidence and Future Directions

Author:

Pagano Duilio1ORCID,Badami Ester23ORCID,Zito Giovanni2ORCID,Conaldi Pier Giulio2ORCID,Vella Ivan1ORCID,Buscemi Barbara4,Amico Giandomenico3ORCID,Busà Rosalia2,Salis Paola4,Li Petri Sergio1,di Francesco Fabrizio1,Calamia Sergio1,Bonsignore Pasquale1,Tropea Alessandro1,Accardo Caterina1,Piazza Salvatore1,Gruttadauria Salvatore15ORCID

Affiliation:

1. Abdominal Surgery and Organ Transplant Unit, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), University of Pittsburgh Medical Center Italy (UPMCI), 90127 Palermo, Italy

2. Department of Laboratory Medicine and Advanced Biotechnologies, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), 90127 Palermo, Italy

3. Ri.MED Foundation, 90133 Palermo, Italy

4. Nephrology Unit, Department for the Treatment and Study of Abdominal Diseases and Abdominal Transplantation, Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS)-Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), University of Pittsburgh Medical Center Italy (UPMCI), 90127 Palermo, Italy

5. Department of Surgery and Surgical and Medical Specialties, University of Catania, 95124 Catania, Italy

Abstract

Background: Ischemia/reperfusion injury (IRI), acute rejection (AR), and delayed graft function (DGF) might occur as major complications following kidney transplantation. Thus, the identification of biomarkers for the IRI, AR, and/or DGF development becomes crucial as it may help to guide post-transplant management. Natural killer (NK) cells, hepatic interstitial T-lymphocytes (T-Li), and NK-T cells are crucial in both innate and adaptive immunity after abdominal solid organ transplantation. Hence, the aim of this study was to evaluate the impact of the immune system after graft reperfusion during KT in adults in order to identify predictive biomarkers. Methods: The NK, T-Li, and NK-T phenotypes and concentrations were retrospectively analyzed in a consecutive series of liver perfusates obtained after organ procurement flushing the abdominal cavity recovered from deceased brain donors (DBDs). Their percentage was compared with the renal transplant recipients’ characteristics with kidneys taken from the same DCDs. The hepatic perfusate cells were purified by density gradient centrifugation. Flow cytometric investigation was used to determine their phenotype with the following immunological markers in order to determine the relative percentage of T-Li, NK-T, and NK cells: CD3, CD4, CD8, and CD56. Results: 42 DBDs’ liver perfusates were analyzed. The related clinical outcomes of kidney transplant recipients from 2010 to 2020 performed at our Institute were evaluated. Time in days of delayed functional recovery of transplanted kidneys (DGF) (p = 0.02) and the onset of secondary infection from a cytomegalovirus (p = 0.03) were significantly associated with the T-Li percentage. An increased relative risk (HR) of organ survival was significantly associated with the percent cell concentration of T-Li and time to DGF, on COX analysis, were (HR = 1.038, p = 0.04; and HR = 1.029, p = 0.01, respectively). None relevant clinical outcomes in kidney transplant patients were associated with the specificity of the NK and NK-T cell proportions. Conclusions: A new potential role of T-Li cells was detected in the context of hepatic perfusate from DBDs. It could detect potential impacts in organ allocation, surgical procuring techniques, and in the analysis of IRI pathophysiological events.

Publisher

MDPI AG

Subject

General Medicine

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