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Th1, Th2, Th17 cell subsets in two different immunosuppressive protocols in renal allograft recipients (Sirolimus vs mycophenolate mofetil): A cohort study
Institution:1. Department of Immunology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran;2. Chronic Kidney Disease Research Center, Labbafinejad Medical Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran;3. Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran;4. Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran;5. Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;1. Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Valladolid, Valladolid, Spain;2. Department of Nephrology, Hospital Virgen de la Concha, Sanidad de Castilla y León, Zamora, Spain;3. Internal Medicine, Kliniken Nordoberpfalz AG, Bayern, Germany;4. Intensive Care Medicine, Hospital Virgen de la Concha, Sanidad de Castilla y León, Zamora, Spain;5. Hematology, University Hospital of Basel, Basel, Switzerland;6. Woodland Medical Practice, NHS, Lincolnshire, United Kingdom;7. Nephrology, Hospital del Mar, Barcelona, Spain;8. Centre de Transplantation d''Organes, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland;9. Immunology, Hospital Universitario Marqués de Valdecilla, Santander, Spain;10. Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands;11. CEIm Área de Salud Valladolid Este, Hospital Clínico Universitario de Valladolid, Valladolid, Spain;12. Clinical Epidemiology Research Support, Sanidad de Castilla y León, Zamora, Spain;13. Immunology, Centre Hospitalier Universitaire de Saint-Etienne, Saint-Priest-en-Jarez, France;1. Department of Plastic & Reconstructive Surgery, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea;2. Department of Biomedical Engineering, Seoul National University College of Medicine, Seoul 03080, Republic of Korea;1. Department of Thoracic Surgery, The First Affiliated Hospital of Xi''an Jiaotong University, Xi''an, Shaanxi Province 710061, China;2. Department of Radiation Oncology, The First Affiliated Hospital of Xi''an Jiaotong University, Xi''an, Shaanxi Province 710061, China
Abstract:Long-term use of calcineurin inhibitors (CNI) is associated with nephrotoxicity, which is an important cause of renal dysfunction. Therefore, CNI-minimization strategies which decrease the CNI nephrotoxicity under the protection of additional immunosuppressant drugs have been developed. The aim of current cohort study was to compare the effect of two immunosuppressive protocols tacrolimus (TAC) in combination with mycophenolate mofetil (MMF) and prednisolone (PRED) versus TAC in combination with sirolimus (SRL) and prednisolone] on the frequency of T helper cell subsets (Th1, Th2 and Th17 cells) and their associated cytokine (IFN-γ, IL-4 and IL-17A) levels in renal allograft recipients.In this study, renal transplant recipients who received induction therapy (Antithymocyte globulin) and were also on triple immunosuppressive therapy were included and divided in to two groups: Group A was comprised 14 patients who received TAC, MMF and PERD whereas group B was composed of 10 patients who received TAC, SRL and PERD. The frequency of Th1, Th2 and Th17 cells in the peripheral blood mononuclear cells (PBMCs) of the patients was analyzed by flow cytometry before and 4 months after transplantation. In addition, IFN-γ, IL-4 and IL-17A concentrations in PBMC culture supernatants of patients before and 4 months after transplantation were quantified by ELISA.The results of our study showed that TAC, MMF and PRED protocol did not diminish the frequency of Th17 cells at 4 months post-transplantation (5% ± 2.5) compared with pre-transplantation (2.3% ± 1; P < 0.05). However, Th17 (3.6% ± 1.5 pre-transplantation vs 2.2% ± 0.9 at 4 months post-transplantation; P < 0.05), Th2 (1.4% ± 0.3 pre-transplantation vs 0.8% ± 0.4 at 4 months post-transplantation; P < 0.05) cell subsets and IL-4 concentration (71.5 pg/ml ± 12 pre-transplantation vs 62.5 pg/ml ±4.4 at 4 months post-transplantation; P < 0.05) were significantly decreased after transplantation in patients who had received SRL, TAC and PRED.In conclusion, the data of the current study suggest that using reduced dose of TAC in SRL, TAC and PRED protocol is in favor of allograft survival; however a cohort study with larger sample size is needed for confirming our results.
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