Epstein-Barr virus load for early detection of lymphoproliferative disorder in pediatric renal transplant recipients

Clin Nephrol. 2011 Jul;76(1):40-8. doi: 10.5414/cn106572.

Abstract

Aim: The aims of this study were to establish a protocol for monitoring Epstein-Barr virus (EBV) infection for identification of pediatric renal transplant recipients with a high risk of developing posttransplant lymphoproliferative disorder (PTLD) and to predict the development of PTLD.

Subjects and methods: Peripheral blood mononuclear cells (PBMCs) and plasma EBV loads were measured by nested PCR (n-PCR) and real-time PCR (r-PCR) every 1 - 3 months after grafting in 17 pediatric recipients who were seronegative for EBV before grafting (4 with EBV-associated symptoms, including 2 with PTLD (Group A); 6 with asymptomatic persistent high EBV loads in PBMCs of > 1,000 copies/µgDNA for over 6 months (Group B); and 7 with neither EBV-associated symptoms nor persistent high EBV loads in PBMCs (Group C)).

Results: n-PCR revealed EBV-DNA in PBMCs from all patients. The EBV genome was present in plasma in 3 (75%), 1 (17%), and 0 (0%) in Groups A, B and C (p < 0.01 for A vs. B and A vs. C). EBV loads detected by r-PCR in PBMCs were significantly higher in Groups A (p < 0.05) and B (p < 0.01) compared to Group C. EBV genomes in plasma were detected by n- and r-PCR in only the 2 cases with PTLD. One patient with lymphadenitis in Group A and 1 patient in Group B had EBV-DNA in plasma based on n-PCR, but the viral loads using r-PCR were < 250 copies/ml.

Conclusion: EBV loads in PBMCs alone are insufficient for predicting EBV-associated symptoms including PTLD. Plasma EBV loads (over 250 copies/ml) estimated by r-PCR may be useful to distinguish PTLD from other EBV-associated diseases or asymptomatic viremia.

MeSH terms

  • Adolescent
  • Antiviral Agents / therapeutic use
  • Child
  • Child, Preschool
  • Epstein-Barr Virus Infections / complications*
  • Epstein-Barr Virus Infections / drug therapy
  • Female
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / isolation & purification*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation / adverse effects*
  • Lymphoproliferative Disorders / diagnosis*
  • Lymphoproliferative Disorders / etiology
  • Lymphoproliferative Disorders / virology
  • Male
  • Polymerase Chain Reaction
  • Viral Load*

Substances

  • Antiviral Agents
  • Immunosuppressive Agents