Effects of two immunosuppression regimens on T-lymphocyte subsets in elderly kidney transplant recipients.

Autor:	Freitas GRR; Serviço de Transplante Renal, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.; Departamento de transplante renal, Hospital Universitário de Brasília (HUB), Empresa Brasileira de Serviços Hospitalares (EBSERH), Brasília, Brazil., Fernandes MDL; Serviço de Transplante Renal, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Agena F; Serviço de Transplante Renal, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Lemos FBC; Serviço de Transplante Renal, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., de Paula FJ; Serviço de Transplante Renal, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Coelho V; Laboratório de Imunologia, Instituto do Coração, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.; Laboratório de Investigação Médica 19 (LIM-19), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.; Instituto de Investigação em Imunologia, Instituto Nacional de Ciência e Tecnologia (iii-INCT), São Paulo, Brazil., David-Neto E; Serviço de Transplante Renal, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil., Galante NZ; Serviço de Transplante Renal, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Sep 20; Vol. 15, pp. 1405855. Date of Electronic Publication: 2024 Sep 20 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1405855
Abstrakt:	Background: Despite the growing number of elderly kidney transplant (Ktx) recipients, few studies have examined the effects of immunosuppression on their lymphocyte profiles. Methods: We evaluated the early conversion from mycophenolate sodium (MPS) to everolimus (EVL) after rabbit antithymocyte globulin (rATG) 2 mg/kg induction in elderly kidney recipients. Three groups of KTx patients were compared: (a) Young (n=20, 36 ± 7 y) receiving standard immunosuppression (Group A1) (prednisone, tacrolimus, and MPS), (b) Elderly (n=35, 65 ± 3 y) receiving standard immunosuppression (Group B1), and (c) Elderly (n=16, 65 ± 3 y) with early (mean 30 d) conversion from MPS to EVL (Group B2). Naive, memory, and regulatory peripheral blood TCD4 + lymphocytes were quantified at 0, 30, and 365 d. Results: Results are reported as [mean(p25-p75)]. Young recipients had higher lymphocyte counts at baseline [2,100(1,630-2,400) vs. 1,310 (1,000-1,600)/mm 3 , p<0.0001] maintained higher counts within 365 d [1,850(1,590-2,120) vs. 1,130(460-1,325)/mm 3 , p=0.018 and vs. 1,410(805-1,895)/mm 3 , p=0.268]. Elderly recipients showed a decrease in lymphocytes within 30 d [1,310(1,000-1,600) vs. 910(700-1,198)/mm 3 , p=0.0012] with recovery within 365 d. The same pattern was observed in total lymphocytes and TCD4 + counts. Rabbit antithymocyte globulin induced a reduction in central memory T-cell percentages at 30 d in both young recipients [6.2(3.77-10.8) vs. 5.32(2.49-7.28)% of CD4 + , p=0.036] and in elderly recipients [8.17(5.28-12.88) vs. 6.74(4.36-11)% of CD4 + , p=0.05] on standard immunosuppression, returning to baseline at 365 d in elderly recipients but not in young recipients. Regulatory T CD39 + cells (Treg) percentages decreased at 30 d in elderly recipients [2.1(1.23-3.51) vs. 1.69(0.8-2.66)% of CD4 + , p=0.0028] and in young recipients [1.29(0.45-1.85) vs. 0.84(0.18-1.82)% of CD4 + , p=0.0038], returning to baseline at 365 d in elderly recipients [2.1(1.23-3.51) vs. 2.042(0.88-2.42)% of CD4 + ], but not in young recipients [1.29(0.45-1.85) vs. 0.86(0.7-1.34) % of CD4 + ]. The elderly everolimus conversion group did not show significant changes in cell profile over time or compared to elderly recipients with standard immunosuppression. Conclusion: Aging favored the maintenance of Treg during the late transplantation period despite ongoing immunosuppression. Lymphocyte depletion due to rATG was more prominent in elderly recipients and affected memory subsets with a temporary reduction in central memory T cells. However, conversion to everolimus did not impact Treg profile. Reducing the dose of rATG in elderly recipients seems necessary for the expected lymphocyte changes with EVL to occur. Clinical Trial Registration: nEverOld Trial, identifier NTC01631058. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Freitas, Fernandes, Agena, Lemos, Paula, Coelho, David-Neto and Galante.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu