PMID- 26227106
OWN - NLM
STAT- MEDLINE
DCOM- 20161025
LR  - 20230124
IS  - 1600-6143 (Electronic)
IS  - 1600-6135 (Print)
IS  - 1600-6135 (Linking)
VI  - 16
IP  - 1
DP  - 2016 Jan
TI  - Nonchimeric HLA-Identical Renal Transplant Tolerance: Regulatory 
      Immunophenotypic/Genomic Biomarkers.
PG  - 221-34
LID - 10.1111/ajt.13416 [doi]
AB  - 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 Immunosuppression was withdrawn by 24 months.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.
CI  - (c) Copyright 2015 The American Society of Transplantation and the American Society 
      of Transplant Surgeons.
FAU - Leventhal, J R
AU  - Leventhal JR
AD  - Comprehensive Transplant Center, Northwestern University, Chicago, IL.
AD  - Department of Surgery-Transplantation, Northwestern University, Chicago, IL.
FAU - Mathew, J M
AU  - Mathew JM
AD  - Comprehensive Transplant Center, Northwestern University, Chicago, IL.
AD  - Department of Surgery-Transplantation, Northwestern University, Chicago, IL.
AD  - Department of Microbiology-Immunology, Northwestern University, Chicago, IL.
FAU - Salomon, D R
AU  - Salomon DR
AD  - Department of Molecular and Experimental Medicine, The Scripps Research 
      Institute, La Jolla, CA.
FAU - Kurian, S M
AU  - Kurian SM
AD  - Department of Molecular and Experimental Medicine, The Scripps Research 
      Institute, La Jolla, CA.
FAU - Friedewald, J J
AU  - Friedewald JJ
AD  - Comprehensive Transplant Center, Northwestern University, Chicago, IL.
AD  - Department of Medicine-Nephrology, Northwestern University, Chicago, IL.
FAU - Gallon, L
AU  - Gallon L
AD  - Comprehensive Transplant Center, Northwestern University, Chicago, IL.
AD  - Department of Medicine-Nephrology, Northwestern University, Chicago, IL.
FAU - Konieczna, I
AU  - Konieczna I
AD  - Comprehensive Transplant Center, Northwestern University, Chicago, IL.
FAU - Tambur, A R
AU  - Tambur AR
AD  - Comprehensive Transplant Center, Northwestern University, Chicago, IL.
AD  - Department of Surgery-Transplantation, Northwestern University, Chicago, IL.
FAU - Charette, J
AU  - Charette J
AD  - Comprehensive Transplant Center, Northwestern University, Chicago, IL.
AD  - Department of Surgery-Transplantation, Northwestern University, Chicago, IL.
FAU - Levitsky, J
AU  - Levitsky J
AD  - Comprehensive Transplant Center, Northwestern University, Chicago, IL.
AD  - Department of Medicine-Hepatology, Northwestern University, Chicago, IL.
FAU - Jie, C
AU  - Jie C
AD  - Comprehensive Transplant Center, Northwestern University, Chicago, IL.
FAU - Kanwar, Y S
AU  - Kanwar YS
AD  - Department of Pathology, Northwestern University, Chicago, IL.
FAU - Abecassis, M M
AU  - Abecassis MM
AD  - Comprehensive Transplant Center, Northwestern University, Chicago, IL.
AD  - Department of Surgery-Transplantation, Northwestern University, Chicago, IL.
AD  - Department of Microbiology-Immunology, Northwestern University, Chicago, IL.
FAU - Miller, J
AU  - Miller J
AD  - Comprehensive Transplant Center, Northwestern University, Chicago, IL.
AD  - Department of Surgery-Transplantation, Northwestern University, Chicago, IL.
LA  - eng
SI  - ClinicalTrials.gov/NCT00619528
GR  - R01 DK025243/DK/NIDDK NIH HHS/United States
GR  - U19 AI063603/AI/NIAID NIH HHS/United States
GR  - R01 DK25243/DK/NIDDK NIH HHS/United States
GR  - U19 AI63603/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20150730
PL  - United States
TA  - Am J Transplant
JT  - American journal of transplantation : official journal of the American Society of 
      Transplantation and the American Society of Transplant Surgeons
JID - 100968638
RN  - 0 (Biomarkers)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers/*analysis
MH  - Female
MH  - Follow-Up Studies
MH  - Gene Expression Profiling
MH  - Genomics/methods
MH  - Glomerular Filtration Rate
MH  - Graft Survival
MH  - HLA Antigens/*genetics/*immunology
MH  - Histocompatibility
MH  - Humans
MH  - Immunophenotyping
MH  - Kidney Failure, Chronic/genetics/*immunology/surgery
MH  - Kidney Function Tests
MH  - *Kidney Transplantation
MH  - Male
MH  - Middle Aged
MH  - Prognosis
MH  - Retrospective Studies
MH  - Risk Factors
MH  - Transplantation Chimera/genetics/*immunology
MH  - Transplantation Tolerance/*immunology
PMC - PMC4718825
MID - NIHMS708021
OTO - NOTNLM
OT  - Biomarker
OT  - bone marrow/hematopoietic stem cell transplantation
OT  - clinical research/practice
OT  - clinical trial
OT  - genomics
OT  - immunobiology
OT  - kidney transplantation/nephrology
OT  - monitoring: immune
OT  - tolerance: clinical
OT  - translational research/science
EDAT- 2015/08/01 06:00
MHDA- 2016/10/26 06:00
PMCR- 2017/01/01
CRDT- 2015/08/01 06:00
PHST- 2015/04/01 00:00 [received]
PHST- 2015/05/14 00:00 [revised]
PHST- 2015/06/02 00:00 [accepted]
PHST- 2015/08/01 06:00 [entrez]
PHST- 2015/08/01 06:00 [pubmed]
PHST- 2016/10/26 06:00 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - S1600-6135(22)00527-5 [pii]
AID - 10.1111/ajt.13416 [doi]
PST - ppublish
SO  - Am J Transplant. 2016 Jan;16(1):221-34. doi: 10.1111/ajt.13416. Epub 2015 Jul 30.