Despite the finding that most macaques express high serologic titers of anti-CMV antibody, susceptibility to disease appears to be variable post-transplant. This observation led us to hypothesize that CMV susceptibility may be associated with macaque origin.

Sixty-four macaques, 32 Indonesian and 32 Mauritian were tested for CMV DNA copy number/50ng DNA extracted from peripheral blood prior to transplant. Significant copy number disparity was observed between Indonesian and Mauritian animals, 209 vs 19, p=0.00005 (ANOVA), respectively, range 0-768. Distribution analyses defined the following quartiles, 0-197 copies, 198-394, 395-591, and 591-768, in which 97% of Mauritians fell in the first quartile vs 56% of Indonesians; 3% Mauritians fell into the second quartile vs 19% Indonesians, with 25% of the Indonesians falling into the highest two quartiles pre-transplant.

Renal transplants were performed in 7 Indonesian macaques (pre-CMV levels ranging from 2-232, mean 81), MHC mismatched by molecular typing, and treated with thymoglobulin 10mg/kg x 4 doses, FK506, days-1-30, trough 8-10 ng/ml, rapamycin days 30 +, trough, 8-10ng/ml. Mean CMV copy number peaked between days 11-18 (mean 3,773) with 100% mortality by day 60 despite prophylaxis with IV gancilovir, 10mg/kg and oral valcyte, 20mg/kg PO BID. Highest copies in necropsy tissues were found in the transplanted kidney, 894,073, and lung, 55,981/50 ng DNA. Under the same immunosuppression, 3 MHC-mismatched Mauritian kidney recipients and 3 MHC-mismatched islet transplants had first or second quartile CMV copy numbers if detectable and none demonstrated CMV disease by day 35 post-transplant.

In conclusion, the prevalence of CMV copy numbers in the peripheral blood of random sampling of Indonesian macaques of different vendor sources were significantly higher than animals of Mauritian origin. Despite identical immunosuppressive regimens, Indonesian animals experienced a higher incidence of CMV disease post-transplant. Greater genetic and MHC disparity in Indonesian animals may be associated with higher susceptibility to CMV suggesting Indonesian macaques more suited for the study of CMV responses and Mauritians chosen for transplant studies.

« Back to 2015 American Transplant Congress