Cellular and molecular immune profiles in renal transplant recipients after conversion from tacrolimus to sirolimus

Lorenzo Gallon, Opas Traitanon, Nedjema Sustento-Reodica, Joseph Leventhal, M. Javeed Ansari, Ricardo C. Gehrau, Venkatesh Ariyamuthu, Sacha A. De Serres, Antonio Alvarado, Darshika Chhabra, James M. Mathew, Nader Najafian, Valeria Mas

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Tacrolimus and sirolimus are commonly used maintenance immunosuppressants in kidney transplantation. As their effects on immune cells and allograft molecular profiles have not been elucidated, we characterized the effects of tacrolimus to sirolimus conversion on the frequency and function of T cells, and on graft molecular profiles. Samples from renal transplant patients in a randomized trial of 18 patients with late sirolimus conversion and 12 on tacrolimus maintenance were utilized. Peripheral blood was collected at 0, 6, 12, and 24 months post randomization, with T-cell subpopulations analyzed by flow cytometry and T-cell alloreactivity tested by IFN-γ ELISPOT. Graft biopsy samples obtained 24 months post randomization were used for gene expression analysis. Sirolimus conversion led to an increase in CD4 + 25 +++ Foxp3 + regulatory T cells. While tacrolimus-maintained patients showed a decrease in indirect alloreactivity over time post transplant, sirolimus conversion increased indirect alloreactive T-cell frequencies compared with tacrolimus-maintained patients. No histological differences were found in graft biopsies, but molecular profiles showed activation of the antigen presentation, IL-12 signaling, oxidative stress, macrophage-derived production pathways, and increased inflammatory and immune response in sirolimus-converted patients. Thus, chronic immune alterations are induced after sirolimus conversion. Despite the molecular profile being favorable to calcineurin inhibitor-based regimen, there was no impact in renal function over 30 months of follow-up.

Original languageEnglish (US)
Pages (from-to)828-838
Number of pages11
JournalKidney International
Volume87
Issue number4
DOIs
StatePublished - Jan 1 2015

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Tacrolimus
Sirolimus
Kidney
Transplants
T-Lymphocytes
Random Allocation
Maintenance
Biopsy
Enzyme-Linked Immunospot Assay
Antigen Presentation
Regulatory T-Lymphocytes
Interleukin-12
Immunosuppressive Agents
Transplant Recipients
Kidney Transplantation
Allografts
Flow Cytometry
Oxidative Stress
Macrophages
Gene Expression

ASJC Scopus subject areas

  • Medicine(all)
  • Nephrology

Cite this

Gallon, L., Traitanon, O., Sustento-Reodica, N., Leventhal, J., Ansari, M. J., Gehrau, R. C., ... Mas, V. (2015). Cellular and molecular immune profiles in renal transplant recipients after conversion from tacrolimus to sirolimus. Kidney International, 87(4), 828-838. https://doi.org/10.1038/ki.2014.350

Cellular and molecular immune profiles in renal transplant recipients after conversion from tacrolimus to sirolimus. / Gallon, Lorenzo; Traitanon, Opas; Sustento-Reodica, Nedjema; Leventhal, Joseph; Ansari, M. Javeed; Gehrau, Ricardo C.; Ariyamuthu, Venkatesh; De Serres, Sacha A.; Alvarado, Antonio; Chhabra, Darshika; Mathew, James M.; Najafian, Nader; Mas, Valeria.

In: Kidney International, Vol. 87, No. 4, 01.01.2015, p. 828-838.

Research output: Contribution to journalArticle

Gallon, L, Traitanon, O, Sustento-Reodica, N, Leventhal, J, Ansari, MJ, Gehrau, RC, Ariyamuthu, V, De Serres, SA, Alvarado, A, Chhabra, D, Mathew, JM, Najafian, N & Mas, V 2015, 'Cellular and molecular immune profiles in renal transplant recipients after conversion from tacrolimus to sirolimus', Kidney International, vol. 87, no. 4, pp. 828-838. https://doi.org/10.1038/ki.2014.350
Gallon L, Traitanon O, Sustento-Reodica N, Leventhal J, Ansari MJ, Gehrau RC et al. Cellular and molecular immune profiles in renal transplant recipients after conversion from tacrolimus to sirolimus. Kidney International. 2015 Jan 1;87(4):828-838. https://doi.org/10.1038/ki.2014.350
Gallon, Lorenzo ; Traitanon, Opas ; Sustento-Reodica, Nedjema ; Leventhal, Joseph ; Ansari, M. Javeed ; Gehrau, Ricardo C. ; Ariyamuthu, Venkatesh ; De Serres, Sacha A. ; Alvarado, Antonio ; Chhabra, Darshika ; Mathew, James M. ; Najafian, Nader ; Mas, Valeria. / Cellular and molecular immune profiles in renal transplant recipients after conversion from tacrolimus to sirolimus. In: Kidney International. 2015 ; Vol. 87, No. 4. pp. 828-838.
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