PMID- 22186938
OWN - NLM
STAT- MEDLINE
DCOM- 20120309
LR  - 20240321
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Print)
IS  - 0041-1337 (Linking)
VI  - 93
IP  - 3
DP  - 2012 Feb 15
TI  - Pretransplant immune regulation predicts allograft outcome: bidirectional 
      regulation correlates with excellent renal transplant function in living-related 
      donor-recipient pairs.
PG  - 283-90
LID - 10.1097/TP.0b013e31823e46a0 [doi]
AB  - BACKGROUND: Tolerance to noninherited maternal antigens has provided clinical 
      advantage when kidney transplants are exchanged between siblings but not when 
      mother herself is the donor. This paradox prompted us to revisit the "two-way" 
      hypothesis of transplant tolerance--that the immune status of both the organ 
      recipient and the organ donor critically influences allograft outcome. METHODS: 
      We obtained peripheral blood monocyte cells from 29 living donor-recipient pairs 
      before transplant and used the trans-vivo-delayed type hypersensitivity assay to 
      measure immune regulation in both the recipient antidonor and donor antirecipient 
      directions. RESULTS: We found preexisting bidirectional regulation in all human 
      leukocyte antigen (HLA)-identical sibling pairs tested (7/7), and one half (9/18) 
      of the HLA haploidentical pairs. No significant regulation was found in four 
      control living unrelated and two HLA haploidentical living-related donor 
      recipient pairs, whereas unidirectional regulation was found in the remaining 
      seven haploidentical pairs. Of the nine HLA haploidentical transplants with 
      unidirectional or no pretransplant regulation, seven had an acute rejection 
      episode and four of these experienced graft loss. In contrast, of the nine HLA 
      haploidentical transplants with bidirectional regulation, only one had rejection. 
      Renal function for the latter group was similar to HLA-identical kidney 
      recipients at 3 years posttransplant. Significantly (P<0.05) lower mean serum 
      creatinine values in bidirectional regulators were noted as early as 4 months and 
      this difference became more pronounced at 12 (P<0.005) and 36 months (P<0.0001). 
      CONCLUSIONS: Contrary to the belief that only the recipient's immune status 
      matters, the data indicate that pretransplant immune status of both donor and 
      recipient influence posttransplant outcome.
FAU - Jankowska-Gan, Ewa
AU  - Jankowska-Gan E
AD  - Division of Transplantation, Department of Surgery, University of Wisconsin 
      School of Medicine and Public Health, Madison, WI, USA.
FAU - Sheka, Adam
AU  - Sheka A
FAU - Sollinger, Hans W
AU  - Sollinger HW
FAU - Pirsch, John D
AU  - Pirsch JD
FAU - Hofmann, R Michael
AU  - Hofmann RM
FAU - Haynes, Lynn D
AU  - Haynes LD
FAU - Armbrust, Michael J
AU  - Armbrust MJ
FAU - Mezrich, Joshua D
AU  - Mezrich JD
FAU - Burlingham, William J
AU  - Burlingham WJ
LA  - eng
GR  - UL1 RR025011-01/RR/NCRR NIH HHS/United States
GR  - R01 AI066219-04/AI/NIAID NIH HHS/United States
GR  - 1UL1RR025011/RR/NCRR NIH HHS/United States
GR  - UL1 RR025011/RR/NCRR NIH HHS/United States
GR  - R01 AI066219/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
SB  - IM
CIN - Transplantation. 2012 Feb 15;93(3):247-8. PMID: 22179406
MH  - Adult
MH  - Animals
MH  - Female
MH  - Glomerular Filtration Rate
MH  - Haplotypes
MH  - Histocompatibility Testing
MH  - Humans
MH  - Immune Tolerance
MH  - Kidney Transplantation/*immunology
MH  - *Living Donors
MH  - Male
MH  - Mice
MH  - Mice, SCID
MH  - Middle Aged
MH  - Siblings
MH  - Transplantation, Homologous
PMC - PMC3366360
MID - NIHMS340259
COIS- No author has any conflict of interest associated with the publication of this 
      manuscript.
EDAT- 2011/12/22 06:00
MHDA- 2012/03/10 06:00
PMCR- 2013/02/15
CRDT- 2011/12/22 06:00
PHST- 2011/12/22 06:00 [entrez]
PHST- 2011/12/22 06:00 [pubmed]
PHST- 2012/03/10 06:00 [medline]
PHST- 2013/02/15 00:00 [pmc-release]
AID - 10.1097/TP.0b013e31823e46a0 [doi]
PST - ppublish
SO  - Transplantation. 2012 Feb 15;93(3):283-90. doi: 10.1097/TP.0b013e31823e46a0.