Development of CMV-specific cytotoxic T cells (CMV-Tc) in pediatric renal transplant recipients with CMV viremia

Pediatr Transplant. 2021 Dec;25(8):e14119. doi: 10.1111/petr.14119. Epub 2021 Aug 14.

Abstract

Background: Viral infections are controlled primarily by viral-specific T cells, raising concern for adequate T-cell response to clear CMV infection in transplant recipients receiving lymphocyte-depleting agents (LDA). We examined the rates of CMV viremia and clearance, seroconversion, and CMV-specific CD8+ T cell (CMV-Tc) activity with class of induction agent received.

Methods: Retrospective review of 45 pediatric renal transplant recipients who received induction with LDA (n = 31) or non-LDA (NLDA; n = 14) received valganciclovir prophylaxis for 6 months post-transplant and CMV-PCR monitoring. CMV-Tc was measured by intracellular IFNγ flow cytometry, when possible, at baseline, 1 month after CMV viremia (>5 copies/PCR) and serially until CMV-Tc was positive (≥0.2%).

Results: Viremia rates at 1, 2, and 4 years post-transplant were higher in LDA vs. NLDA (46.3% vs. 7.2%, 64.2% vs. 7.2%, and 64.2% vs. 7.2%, respectively; p = .002). Viremia rates at these time points in seronegative LDA (50.3%, 71.6%, 71.6%) were significantly or near significantly higher than seronegative NLDA (9.1%, 9.1%, 9.1%; p = .004), seropositive-LDA (22.3%, 22.3%, 22.3%; p = .07), or seropositive NLDA (0%, 0%, 0%; p = .07). Eleven of 17 (64.7%) viremic subjects required valganciclovir dose reduction during the prophylaxis period for leukopenia. All viremic LDA patients developed CMV-Tc. One viremic NLDA patient did not develop CMV-Tc. No patients developed CMV disease.

Conclusion: CMV seronegative pediatric renal transplant patients receiving LDA are more likely to have valganciclovir prophylaxis dose reduction and develop subclinical CMV viremia; however, all developed CMV-Tc. Larger prospective studies are needed to further understand the effects of induction agents on CMV-Tc and CMV-Tc's role post-transplant.

Keywords: cytomegalovirus; induction agent; pediatric; renal transplantation; viremia.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Antiviral Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Cytomegalovirus Infections / prevention & control*
  • Female
  • Graft Rejection / prevention & control
  • Humans
  • Infant
  • Kidney Transplantation*
  • Lymphocyte Depletion
  • Male
  • Postoperative Complications / prevention & control*
  • Postoperative Complications / virology
  • Retrospective Studies
  • T-Lymphocytes, Cytotoxic / immunology*
  • Transplant Recipients
  • Transplantation, Homologous
  • Valganciclovir / therapeutic use*
  • Viremia / virology*
  • Young Adult

Substances

  • Antiviral Agents
  • Valganciclovir