title: Pretransplant immune regulation predicts allograft outcome:  bidirectional regulation correlates with excellent renal transplant function in living-related donor-recipient pairs.
abstract: 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.
authors.affiliation: Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
authors.forename: Ewa
authors.initials: E
authors.lastname: Jankowska-Gan
authors.forename: Adam
authors.initials: A
authors.lastname: Sheka
authors.forename: Hans W
authors.initials: HW
authors.lastname: Sollinger
authors.forename: John D
authors.initials: JD
authors.lastname: Pirsch
authors.forename: R Michael
authors.initials: RM
authors.lastname: Hofmann
authors.forename: Lynn D
authors.initials: LD
authors.lastname: Haynes
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Armbrust
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Mezrich
authors.forename: William J
authors.initials: WJ
authors.lastname: Burlingham
mesh_terms: D000328:Adult; D000818:Animals; D005260:Female; D005919:Glomerular Filtration Rate; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D007108:Immune Tolerance; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D035781:Siblings; D014184:Transplantation, Homologous