title: Monitoring antidonor alloantibodies as a predictive assay for renal allograft tolerance/long-term observations in nonhuman primates.
abstract: BACKGROUND
  In an effort to define reliable assays that might predict postimmunosuppressant-withdrawal development of chronic rejection (CR), despite conditioning for tolerance induction, we evaluated various immunological responses in nonhuman primate renal allograft recipients.
  
  
  METHODS
  Fourteen Cynomolgus monkeys received low dose total body irradiation, thymic irradiation, antithymocyte globulin, and peritransplant CD154 blockade, followed by a one-month course of cyclosporine. Recipients underwent major histocompatibility complex mismatched kidney transplantation with donor bone marrow infusion (Group A, n=8), without donor cell infusion (Group B, n=2), or with donor splenocyte infusion (Group C, n=4).
  
  
  RESULTS
  All Group A recipients developed mixed chimerism and four of them survived long-term without rejection. The remaining four rejected their kidney allografts either chronically or acutely. All recipients in Groups B and C failed to develop chimerism and rejected their allografts. Among various in vitro assays, detection of anti-donor alloantibody (ADA) by flow cytometry (FCM) was the most relevant to long-term outcome. All five recipients that developed both anti-T cell and B cell IgG ADA in Groups A, B and C, developed histological evidence of CR within 200 days of the appearance of ADA. One of two recipients that developed only anti-B cell IgG ADA eventually developed CR over two years following discontinuation of immunosuppression and 1.5 years after ADA development. Another recipient with very low anti-B cell ADA has never developed CR.
  
  
  CONCLUSIONS
  ADA monitoring with FCM assay appears to be useful in predicting the failure of tolerance prior to the development of functional or histologic abnormalities of the renal allograft.
authors.affiliation: Department of Surgery, Transplantation Unit, Harvard Medical School at Massachusetts General Hospital, Boston, MA 02114, USA. sboskovic@partners.org
authors.forename: Svjetlan
authors.initials: S
authors.lastname: Boskovic
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kawai
authors.forename: Rex-Neal
authors.initials: RN
authors.lastname: Smith
authors.forename: Siew-Lin
authors.initials: SL
authors.lastname: Wee
authors.forename: Ognjenka
authors.initials: O
authors.lastname: Nadazdin
authors.forename: Ichiro
authors.initials: I
authors.lastname: Koyama
authors.forename: Susan
authors.initials: S
authors.lastname: Saidman
authors.forename: Francesca
authors.initials: F
authors.lastname: Cardarelli
authors.forename: Nahel
authors.initials: N
authors.lastname: Elias
authors.forename: Megan
authors.initials: M
authors.lastname: Sykes
authors.forename: Terry
authors.initials: T
authors.lastname: Strom
authors.forename: Robert B
authors.initials: RB
authors.lastname: Colvin
authors.forename: David H
authors.initials: DH
authors.lastname: Sachs
authors.forename: A Benedict
authors.initials: AB
authors.lastname: Cosimi
mesh_terms: D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D006085:Graft Survival / Q000276:immunology*; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D007518:Isoantibodies / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008252:Macaca fascicularis; D008297:Male; D023421:Models, Animal; D008991:Monitoring, Physiologic; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
chemical_list: D007518:Isoantibodies