Preservation of Antiviral Immunologic Efficacy Without Alloimmunity After Switch to Belatacept in Calcineurin Inhibitor-Intolerant Patients

Joanna Schaenman; Maura Rossetti; Harry Pickering; Gemalene Sunga; Holly Wilhalme; David Elashoff; Qiuheng Zhang; Michelle Hickey; Uttam Reddy; Gabriel Danovitch; Elaine F Reed; Suphamai Bunnapradist

doi:10.1016/j.ekir.2022.10.015

Preservation of Antiviral Immunologic Efficacy Without Alloimmunity After Switch to Belatacept in Calcineurin Inhibitor-Intolerant Patients

Kidney Int Rep. 2022 Oct 20;8(1):126-140. doi: 10.1016/j.ekir.2022.10.015. eCollection 2023 Jan.

Affiliations

¹ Division of Infectious Disease, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
² Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
³ Department of Medicine Biostatistics Core, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
⁴ Division of Kidney Transplantation, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.

Abstract

Introduction: Belatacept has shown potential for prevention of rejection after kidney transplantation, given its demonstration of reduced nephrotoxicity in combination with absence of significant incidence of rejection. However, concerns have been raised regarding increased risk of viral infection.

Methods: We set out to explore the impact of the switch to belatacept on alloimmune and antiviral immunity through the study of patients switched from calcineurin inhibitor (CNI) to belatacept within 3 months of kidney transplantation compared with a matched cohort of control patients on a CNI-based regimen.

Results: After the switch to belatacept, immune phenotyping demonstrated a decrease in naive and an increase in terminally differentiated effector memory (TMRA) T cells, with no significant difference compared with control patients. Donor-specific immune response, measured by intracellular cytokine staining (ICS), did not change significantly either by single or double cytokine secretion, but it was associated with the appearance of donor-specific antibody (DSA) in the control but not the belatacept cohort (P = 0.039 for naive and P = 0.002 for TMRA subtypes). Increased incidence of de novo DSA development was observed in the control group (P = 0.035). Virus-specific immune response, as measured by ICS in response to cytomegalovirus (CMV) or Epstein-Barr virus (EBV), was similar in both groups and stable over time.

Conclusion: We found that belatacept use was associated with an absence of alloreactivity without impact on immune phenotype, while preserving the antiviral immune response, for patients switched from a CNI-based regimen. In parallel, the antiviral immune response against CMV and EBV was preserved after the belatacept switch (clinicaltrials.gov: NCT01953120).

Keywords: CMV; T cell; belatacept; immunosuppression; transplantation.

Associated data

ClinicalTrials.gov/NCT01953120