Monitoring antidonor alloantibodies as a predictive assay for renal allograft tolerance/long-term observations in nonhuman primates.
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.
Boskovic
Svjetlan
S
Department of Surgery, Transplantation Unit, Harvard Medical School at Massachusetts General Hospital, Boston, MA 02114, USA. sboskovic@partners.org
Kawai
Tatsuo
T
Smith
Rex-Neal
RN
Wee
Siew-Lin
SL
Nadazdin
Ognjenka
O
Koyama
Ichiro
I
Saidman
Susan
S
Cardarelli
Francesca
F
Elias
Nahel
N
Sykes
Megan
M
Strom
Terry
T
Colvin
Robert B
RB
Sachs
David H
DH
Cosimi
A Benedict
AB
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
D007518:Isoantibodies