Session Time: 3:15pm-4:45pm
Presentation Time: 3:51pm-4:03pm
*Purpose: This investigator-initiated study examines the impact of belatacept on T cell immune phenotype and function.
*Methods: 19 patients with evidence of calcineurin inhibitor (CNI) toxicity were switched to belatacept as part of a clinical trial to evaluate the immunologic impact of belatacept switch (NCT01953120). Belatacept was dosed at 5mg/kg q2 two weeks for 2 months, and then monthly for 10 months; calcineurin inhibitor (CNI) was tapered off over 4 weeks. Mycophenolate mofetil and prednisone were continued per protocol. Patients were matched based on age, induction, and donor type with 19 control patients. Immune phenotype was analyzed by multiparameter flow cytometry. Antigen response was determined by intracellular cytokine secretion (ICS) assessment using donor cells, or overlapping peptides representing the most immunodominant CMV or EBV antigens. Third party donor cells were used as negative control for alloimmunity assessment.
*Results: Results: Immune phenotype (maturation subtype, T regulatory cells, activation, immune senescence, exhaustion) for CD4+ and CD8+ T cells was similar at the time of study enrollment compared with 3, 6, and 12 months after belatacept start. Interestingly, for control patients maintained on a CNI-containing regimen, the frequency of senescent CD8+ T cells was observed to increase over the 12 month period of study (CD57+CD28-), while the frequency of naïve CD4+ and CD8+ T cells was found to decrease. Alloreactivity by ICS assessment was low to undetectable at study enrollment, and did not increase significantly in either belatacept and control patients. Antiviral immunity against CMV and EBV did not decrease significantly after switch. There were no significant episodes of infection; four patients were treated for acute rejection (1 belatacept, 3 controls).
*Conclusions: This immunologic evaluation of patients switched to belatacept compared with control patients maintained on standard immunosuppression did not find significant impact on immune phenotype, alloreactive immunity, or antiviral immune response This may explain the mechanism behind costimulation blockade effect on alloimmunity without adverse infectious complications.
To cite this abstract in AMA style:Schaenman J, Rossetti M, Wilhalme H, Groysberg V, Sunga G, Gadzhyan J, Abdalla B, Lum E, Pham P, Danovitch G, Veale J, Gritsch HA, Elashoff D, Reed E, Bunnapradist S. Stability of Immune Phenotype, Alloreactive, and Antiviral Immunity after Switch to Belatacept-Based Regimen after Kidney Transplantation [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/stability-of-immune-phenotype-alloreactive-and-antiviral-immunity-after-switch-to-belatacept-based-regimen-after-kidney-transplantation-2/. Accessed March 3, 2021.
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