Desensitization to remove donor specific antibody (DSA) is a way to expand the pool of potential donors for sensitized patients. This study compared the effects of desensitization on humoral alloimmunity to humoral CMV immunity in allosensitized nonhuman primates. Nonhuman primates (Macaca mulatta) were sensitized with two allogeneic skin transplants and treated with carfilzomib (CFZ) and tocilizumab (TCZ) for desensitization. Kidney transplants from the same donor were performed with anti-CD4/CD8 induction; tacrolimus, MMF, and steroid maintenance immunosuppression; and valganciclovir or ganciclovir viral prophylaxis. The DSA was measured by flow cytometry crossmatch, and rhCMV-gB IgG levels were measured by ELISA. Total cell counts in peripheral blood were measured by flow cytometry. There was no significant difference in rhCMV-gB IgG ED50 (6235 ± 2339 vs. 5447 ± 2339; n=6) at times pre- and post-desensitization. There was a significant difference in DSA (MFI 5775 ± 349 vs. 3713 ± 449; n=6; p<0.01) at times pre- and post-desensitization (See Figure 1). No significant differences were found in CD4+ T cell numbers (0.08 ± 0.02 x10³/[mu]L vs. 0.07 ± 0.03 x10³/[mu]L; n=4), CD20+ B cell numbers (0.15 ± 0.01 x10³/[mu]L vs. 0.24 ± 0.11 x10³/[mu]L; n=4), or rhCMV-gB IgG ED50 (9284 ± 5984 vs. 6792 ± 2377; n=4) at post-op week 0 vs. post-op week 2 after kidney transplant. Significant differences were found in CD8+ T cell numbers (0.42 ± 0.09 x10³/[mu]L vs. 0 ± 0 x10³/[mu]L; n=4; p<0.05) at post-op week 0 vs. post-op week 2 after kidney transplant. CMV reactivation with viremia was observed in 4 subjects, and 2 subjects had CMV disease after kidney transplant. Dual targeting desensitization with CFZ and TCZ significantly decreased DSA while leaving CMV specific antibodies unaffected. However, a significant number of recipients developed CMV reactivation after kidney transplantation. These results demonstrate some selectivity in dual targeting desensitization, but demonstrate the importance of preserving cellular immunity for controlling CMV in the sensitized nonhuman primate.

CITATION INFORMATION: Schroder P., Ezekian B., Saccoccio F., Yoon J., Dennis M., Freischlag K., Kwun J., Permar S., Knechtle S. Humoral Immunity to CMV Remains Intact after Dual Targeting Desensitization in Allosensitized Nonhuman Primates Am J Transplant. 2017;17 (suppl 3).

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