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Nonchimeric HLA-Identical Renal Transplant Tolerance: Regulatory Immunophenotypic/Genomic Biomarkers.
Leventhal, J R; Mathew, J M; Salomon, D R; Kurian, S M; Friedewald, J J; Gallon, L; Konieczna, I; Tambur, A R; Charette, J; Levitsky, J; Jie, C; Kanwar, Y S; Abecassis, M M; Miller, J.
Afiliação
  • Leventhal JR; Comprehensive Transplant Center, Northwestern University, Chicago, IL.
  • Mathew JM; Department of Surgery-Transplantation, Northwestern University, Chicago, IL.
  • Salomon DR; Comprehensive Transplant Center, Northwestern University, Chicago, IL.
  • Kurian SM; Department of Surgery-Transplantation, Northwestern University, Chicago, IL.
  • Friedewald JJ; Department of Microbiology-Immunology, Northwestern University, Chicago, IL.
  • Gallon L; Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA.
  • Konieczna I; Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA.
  • Tambur AR; Comprehensive Transplant Center, Northwestern University, Chicago, IL.
  • Charette J; Department of Medicine-Nephrology, Northwestern University, Chicago, IL.
  • Levitsky J; Comprehensive Transplant Center, Northwestern University, Chicago, IL.
  • Jie C; Department of Medicine-Nephrology, Northwestern University, Chicago, IL.
  • Kanwar YS; Comprehensive Transplant Center, Northwestern University, Chicago, IL.
  • Abecassis MM; Comprehensive Transplant Center, Northwestern University, Chicago, IL.
  • Miller J; Department of Surgery-Transplantation, Northwestern University, Chicago, IL.
Am J Transplant ; 16(1): 221-34, 2016 Jan.
Article em En | MEDLINE | ID: mdl-26227106
ABSTRACT
We previously described early results of a nonchimeric operational tolerance protocol in human leukocyte antigen (HLA)-identical living donor renal transplants and now update these results. Recipients given alemtuzumab, tacrolimus/MPA with early sirolimus conversion were multiply infused with donor hematopoietic CD34(+) stem cells. Immunosuppression was withdrawn by 24 months. Twelve months later, operational tolerance was confirmed by rejection-free transplant biopsies. Five of the first eight enrollees were initially tolerant 1 year off immunosuppression. Biopsies of three others after total withdrawal showed Banff 1A acute cellular rejection without renal dysfunction. With longer follow-up including 5-year posttransplant biopsies, four of the five tolerant recipients remain without rejection while one developed Banff 1A without renal dysfunction. We now add seven new subjects (two operationally tolerant), and demonstrate time-dependent increases of circulating CD4(+) CD25(+++) CD127(-) FOXP3(+) Tregs versus losses of Tregs in nontolerant subjects (p < 0.001). Gene expression signatures, developed using global RNA expression profiling of sequential whole blood and protocol biopsy samples, were highly associative with operational tolerance as early as 1 year posttransplant. The blood signature was validated by an external Immune Tolerance Network data set. Our approach to nonchimeric operational HLA-identical tolerance reveals association with Treg immunophenotypes and serial gene expression profiles.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Biomarcadores / Transplante de Rim / Quimeras de Transplante / Tolerância ao Transplante / Antígenos HLA / Falência Renal Crônica Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Transplant Assunto da revista: TRANSPLANTE Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Israel

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Biomarcadores / Transplante de Rim / Quimeras de Transplante / Tolerância ao Transplante / Antígenos HLA / Falência Renal Crônica Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Am J Transplant Assunto da revista: TRANSPLANTE Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Israel