Ratio between Epstein-Barr viral load and anti-Epstein-Barr virus specific T-cell response as a predictive marker of posttransplant lymphoproliferative disease.
BACKGROUND
Posttransplant lymphoproliferative disease (PTLD) is closely linked to primary Epstein-Barr virus (EBV) infection and a defect of EBV specific cellular immunity is supposed to be the basis of PTLD. However, EBV load is so far the only marker proposed to evaluate PTLD risk, and no study has investigated the role of specific anti-EBV T lymphocytes (EBV-TL).


METHODS
We therefore prospectively measured the EBV-TL by enzyme-linked immunospot (elispot) assay, in correlation to EBV load by real-time quantitative PCR and lymphoproliferation occurrence in 45 liver transplanted children.


RESULTS
EBV load at the time of primary infection was high in all patients irrespective to subsequent emergence of PTLD. Seven patients developed PTLD, all of them following primary EBV infection. All seven had low EBV-TL (<2/mm3) associated with high viral load (>25,000 copies/microg DNA). Both parameters can be combined in a 100% positive predictive index. Healing from lymphoma was characterized by rapid EBV-TL increase concomitant to decreasing viral load. EBV-TL follow-up helped to adapt immunomodulation. No patient had PTLD whenever EBV-TL were above 2/mm3.


CONCLUSIONS
We conclude that high viral load is systematic in patients who underwent primary EBV infection and is indicative of the PTLD risk only if there is low concomitant cellular immune response. Healing from PTLD requires modulation of immunosuppression, and appearance of EBV-TL.
Smets
Françoise
F
Pediatrics Department, Cliniques Universitaires Saint Luc, Brussels, Belgium.
Latinne
Dominique
D
Bazin
Hervé
H
Reding
Raymond
R
Otte
Jean-Bernard
JB
Buts
Jean-Paul
JP
Sokal
Etienne M
EM
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005500:Follow-Up Studies; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D016031:Liver Transplantation / Q000502:physiology*; D008232:Lymphoproliferative Disorders / Q000453:epidemiology* / Q000209:etiology / Q000821:virology; D011183:Postoperative Complications / Q000453:epidemiology*; D011237:Predictive Value of Tests; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D016559:Tacrolimus / Q000627:therapeutic use; D019562:Viral Load
D004279:DNA, Viral; D007166:Immunosuppressive Agents; D016559:Tacrolimus