Purpose: We set out to investigate the impact of switch from calcineurin inhibitor (CNI) to belatacept on T cell mediated allo- and EBV-specific immunity.

Methods: We plan to switch 20 kidney recipients with evidence of CNI toxicity to a belatacept-based regimen dosed at 5mg/kg q2 weeks for 2 months and q 4weeks thereafter; CNI was tapered off over 4 weeks after conversion (NCT 01953120). Mycophenolate mofetil and prednisone were continued per protocol. Alloreactive T- cell memory was assessed by stimulating recipient T cells with irradiated donor B cells or donor cell lysate followed by intracellular cytokine secretion analysis to assess direct and indirect alloreactivity, respectively. EBV-specific immunity was assessed by stimulation with peptide pools from major EBV antigens followed by intracellular cytokine secretion analysis. Immune phenotype was analyzed by multiparameter flow cytometry. Statistical analysis was performed using JMP Pro11.

Results: Eight patients who had completed the study protocol were evaluated. Five patients received basiliximab induction and three ATG; five received deceased-donor transplants. Immune phenotype (maturation subtype, T regulatory cells, activation, immune senescence, exhaustion) for CD4+ and CD8+ T cells did not differ at enrollment compared with 3, 6, and 12 months after belatacept start. Alloreactive immunity as measured by direct and indirect allostimulation was low (median 0%) at baseline and remained low at 3, 6, and 12 months. Anti-EBV immunity was detectable at baseline and maintained at 3, 6, and 12 months after belatacept switch, with a modest increase in IFN-g/TNF-a CD4+ cells at 3 months (0.01% v 0.05%) and 12 months (0.01% v 0.03%) (both p<0.05). There were no significant episodes of infection; one patient required treatment for acute rejection.


Conclusions: This preliminary result demonstrated that switch to belatacept was not associated with increase in the alloreactive immune response or decrement in the anti-EBV immune response. This may explain the mechanism behind costimulation blockade effectiveness without adverse infectious complications or impact on graft function. An additional 12 patients will be analyzed as they complete the study and result will be compared to historical control.

CITATION INFORMATION: Schaenman J, Korin Y, Sidwell T, Groysberg V, Gadzhyan J, Lum E, Reddy U, Huang E, Pham T, Danovitch G, Reed E, Bunnapradist S. Preservation of Alloreactive and Antiviral Immunity After Switch to Belatacept-Based Regimen After Kidney Transplantation. Am J Transplant. 2016;16 (suppl 3).

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