PMID- 32290462 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200928 IS - 2077-0383 (Print) IS - 2077-0383 (Electronic) IS - 2077-0383 (Linking) VI - 9 IP - 4 DP - 2020 Apr 11 TI - Long-Term Redistribution of Peripheral Lymphocyte Subpopulations after Switching from Calcineurin to mTOR Inhibitors in Kidney Transplant Recipients. LID - 10.3390/jcm9041088 [doi] LID - 1088 AB - Classical immunosuppression based on steroids, calcineurin inhibitors, and mycophenolate results in several unwanted effects and unsatisfactory long-term outcomes in kidney transplantation (KT). New immunosuppressors search for fewer adverse events and increased graft survival but may have a distinct impact on graft function and immunological biomarkers according to their mechanism of action. This prospective study evaluates the immunological effect of tacrolimus to serine/threonine protein kinase mechanistic target of rapamycin inhibitors (mTORi) conversion in 29 KT recipients compared with 16 controls maintained on tacrolimus. We evaluated renal function, human leukocyte antigen (HLA) antibodies and peripheral blood lymphocyte subsets at inclusion and at 3, 12, and 24 months later. Twenty immunophenotyped healthy subjects served as reference. Renal function remained stable in both groups with no significant change in proteinuria. Two patients in the mTORi group developed HLA donor-specific antibodies and none in the control group (7% vs. 0%, p = 0.53). Both groups showed a progressive increase in regulatory T cells, more prominent in patients converted to mTORi within the first 18 months post-KT (p < 0.001). All patients showed a decrease in naive B cells (p < 0.001), excepting those converted to mTORi without receiving steroids (p = 0.31). Transitional B cells significantly decreased in mTORi patients (p < 0.001), independently of concomitant steroid treatment. Finally, CD56(bright) and CD94/NK group 2 member A receptor positive (NKG2A(+)) Natural Killer (NK) cell subsets increased in mTORi- compared to tacrolimus-treated patients (both p < 0.001). Patients switched to mTORi displayed a significant redistribution of peripheral blood lymphocyte subpopulations proposed to be associated with graft outcomes. The administration of steroids modified some of these changes. FAU - Llinas-Mallol, Laura AU - Llinas-Mallol L AUID- ORCID: 0000-0003-4696-3331 AD - Department of Nephrology; Hospital del Mar, 08003 Barcelona, Spain. AD - Nephropathies Research Group, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain. FAU - Redondo-Pachon, Dolores AU - Redondo-Pachon D AUID- ORCID: 0000-0002-0458-0052 AD - Department of Nephrology; Hospital del Mar, 08003 Barcelona, Spain. AD - Nephropathies Research Group, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain. FAU - Raich-Regue, Dalia AU - Raich-Regue D AUID- ORCID: 0000-0001-7656-5700 AD - Department of Nephrology; Hospital del Mar, 08003 Barcelona, Spain. AD - Nephropathies Research Group, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain. FAU - Perez-Saez, Maria Jose AU - Perez-Saez MJ AD - Department of Nephrology; Hospital del Mar, 08003 Barcelona, Spain. AD - Nephropathies Research Group, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain. FAU - Yelamos, Jose AU - Yelamos J AD - Department of Immunology, Hospital del Mar, 08003 Barcelona, Spain. FAU - Duran, Xavier AU - Duran X AD - Methodology & Biostatistics Support Unit, IMIM, 08003 Barcelona, Spain. FAU - Faura, Anna AU - Faura A AD - Department of Nephrology; Hospital del Mar, 08003 Barcelona, Spain. AD - Nephropathies Research Group, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain. FAU - Lopez-Botet, Miguel AU - Lopez-Botet M AUID- ORCID: 0000-0003-4882-065X AD - Department of Immunology, Hospital del Mar, 08003 Barcelona, Spain. AD - Immunity and Infection Research Group, IMIM, 08003 Barcelona, Spain. AD - University Pompeu Fabra, 08003 Barcelona, Spain. FAU - Pascual, Julio AU - Pascual J AD - Department of Nephrology; Hospital del Mar, 08003 Barcelona, Spain. AD - Nephropathies Research Group, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain. FAU - Crespo, Marta AU - Crespo M AD - Department of Nephrology; Hospital del Mar, 08003 Barcelona, Spain. AD - Nephropathies Research Group, Hospital del Mar Medical Research Institute (IMIM), 08003 Barcelona, Spain. LA - eng GR - PI10/01370/Instituto de Salud Carlos III/ GR - PI13/00598/Instituto de Salud Carlos III/ GR - PI16/00617/Instituto de Salud Carlos III/ GR - RD12/0021/0024/Instituto de Salud Carlos III/ GR - RD16/0009/0013/Instituto de Salud Carlos III/ GR - Sara Borrell Fellowship/Instituto de Salud Carlos III/ GR - Beca per a la recerca/Fundacio Catalana de Trasplantament/ PT - Journal Article DEP - 20200411 PL - Switzerland TA - J Clin Med JT - Journal of clinical medicine JID - 101606588 PMC - PMC7230655 OTO - NOTNLM OT - NK cells OT - T regulatory cells OT - donor-specific antibody OT - immunophenotype OT - kidney transplantation OT - mTOR inhibitors OT - transitional B cells COIS- The authors of this manuscript declare no competing interests. The results presented in this paper have not been published previously in whole or part, except in abstract format. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. EDAT- 2020/04/16 06:00 MHDA- 2020/04/16 06:01 PMCR- 2020/04/11 CRDT- 2020/04/16 06:00 PHST- 2020/03/06 00:00 [received] PHST- 2020/04/08 00:00 [revised] PHST- 2020/04/08 00:00 [accepted] PHST- 2020/04/16 06:00 [entrez] PHST- 2020/04/16 06:00 [pubmed] PHST- 2020/04/16 06:01 [medline] PHST- 2020/04/11 00:00 [pmc-release] AID - jcm9041088 [pii] AID - jcm-09-01088 [pii] AID - 10.3390/jcm9041088 [doi] PST - epublish SO - J Clin Med. 2020 Apr 11;9(4):1088. doi: 10.3390/jcm9041088.