Longitudinal Analysis of T and B Cell Phenotype and Function in Renal Transplant Recipients with or without Rituximab Induction Therapy |
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Authors: | Elena G Kamburova Hans J P M Koenen Martijn W F van den Hoogen Marije C Baas Irma Joosten Luuk B Hilbrands |
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Institution: | 1. Department of Laboratory Medicine - Medical Immunology, Radboud University Medical Centre, Nijmegen, The Netherlands.; 2. Department of Nephrology, Radboud University Medical Centre, Nijmegen, The Netherlands.; Public Health England, United Kingdom, |
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Abstract: | BackgroundPrevention of rejection after renal transplantation requires treatment with immunosuppressive drugs. Data on their in vivo effects on T- and B-cell phenotype and function are limited.MethodsIn a randomized double-blind placebo-controlled study to prevent renal allograft rejection, patients were treated with tacrolimus, mycophenolate mofetil (MMF), steroids, and a single dose of rituximab or placebo during transplant surgery. In a subset of patients, we analyzed the number and phenotype of peripheral T and B cells by multiparameter flow cytometry before transplantation, and at 3, 6, 12, and 24 months after transplantation.ResultsIn patients treated with tacrolimus/MMF/steroids the proportion of central memory CD4+ and CD8+ T cells was higher at 3 months post-transplant compared to pre-transplant levels. In addition, the ratio between the percentage of central memory CD4+ and CD4+ regulatory T cells was significantly higher up to 24 months post-transplant compared to pre-transplant levels. Interestingly, treatment with tacrolimus/MMF/steroids resulted in a shift toward a more memory-like B-cell phenotype post-transplant. Addition of a single dose of rituximab resulted in a long-lasting B-cell depletion. At 12 months post-transplant, the small fraction of repopulated B cells consisted of a high percentage of transitional B cells. Rituximab treatment had no effect on the T-cell phenotype and function post-transplant.ConclusionsRenal transplant recipients treated with tacrolimus/MMF/steroids show an altered memory T and B-cell compartment post-transplant. Additional B-cell depletion by rituximab leads to a relative increase of transitional and memory-like B cells, without affecting T-cell phenotype and function.Trial RegistrationClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00565331","term_id":"NCT00565331"}}NCT00565331 |
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