title: Sirolimus vs cyclosporine after induction with basiliximab does not promote regulatory T cell expansion in de novo kidney transplantation: Results from a single-center randomized trial.
abstract: Regulatory T cells (Tregs), defined as CD4+CD25+highFoxP3+CD127- cells, could promote tolerance in renal transplantation (Tx). In an open-label, randomized, controlled trial 62 de-novo Tx recipients received induction with basiliximab and cyclosporine A (CsA) for the first month after Tx and then were assigned to treatment with sirolimus (SRL) or CsA and followed up for 2 years. The primary endpoint was to evaluate the effects of induction and maintenance treatments on circulating Tregs, while the secondary endpoint was the assessment of Treg renal infiltration and the relationship between Treg count and clinical outcomes. There were no significant differences in either circulating or tissue Treg number between the two groups. At 1 month post-Tx, all patients presented a profound Treg depletion, followed by a significant increase in Tregs that resulted stable during the follow-up. The same trend was also observed for non-activated Tregs (CD69-) and for other immunocompetent cells (CD4+ and CD8+ T cells, B cells and NK cells). Moreover, the Treg count did not correlate either with renal function or with acute rejection and graft loss. Initial immunosuppression is crucial to regulate circulating Tregs, regardless of subsequent immunosuppressive maintenance regimens. Strategies aiming to promote tolerance should consider the effects of different induction regimens.
authors.affiliation: Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, Italy; University of Pavia, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Libetta
authors.affiliation: Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, Italy; University of Pavia, Italy. Electronic address: pasqualeesposito@hotmail.com.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Esposito
authors.affiliation: Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, Italy; University of Pavia, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Gregorini
authors.affiliation: Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, Italy; University of Pavia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Margiotta
authors.affiliation: Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, Italy; University of Pavia, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Martinelli
authors.affiliation: Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, Italy; University of Pavia, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Borettaz
authors.affiliation: Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, Italy; University of Pavia, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Canevari
authors.affiliation: Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, Italy; University of Pavia, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Rampino
authors.affiliation: Service of Renal Transpantation, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Ticozzelli
authors.affiliation: Service of Renal Transpantation, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Abelli
authors.affiliation: University of Pavia, Italy; Department of Haematological, Pneumological and Cardiovascular Sciences, Fondazione IRCCS Policlinico San Matteo, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Meloni
authors.affiliation: Department of Nephrology, Dialysis and Transplantation, Fondazione IRCCS Policlinico San Matteo, Italy; University of Pavia, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Dal Canton
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D015703:Antigens, CD / Q000378:metabolism; D000077552:Basiliximab; D049109:Cell Proliferation / Q000187:drug effects; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007165:Immunosuppression Therapy; D060828:Induction Chemotherapy; D016030:Kidney Transplantation; D060046:Maintenance Chemotherapy; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects; D020123:Sirolimus / Q000008:administration & dosage* / Q000009:adverse effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D023001:Transplantation Tolerance
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D011993:Recombinant Fusion Proteins; D016572:Cyclosporine; D000077552:Basiliximab; D020123:Sirolimus
keywords: Basiliximab; Cyclosporine A; Kidney transplant; Regulatory T cells; Sirolimus; Transplant outcomes