Use of cytokine polymorphisms and Epstein–Barr virus viral load to predict development of post-transplant lymphoproliferative disorder in paediatric liver transplant recipients

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Clinical TransplantationVolume 20 Page 389 - May/June 2006doi:10.1111/j.1399-0012.2006.00498.x

Volume 20 Issue 3

Use of cytokine polymorphisms and Epstein–Barr virus viral load to predict development of post-transplant lymphoproliferative disorder in paediatric liver transplant recipients

C. Leea, Barbara Savoldob, Neal R. Barshesa, Cliona M. Rooneyb, Helen E. Heslopb, P. Geeb, Yvette Caldwellb, Jaymee D. a and A. Gossa

Lee TC, Savoldo B, Barshes NR, Rooney CM, Heslop HE, Gee AP, Caldwell Y, JD, Goss JA. Use of cytokine polymorphisms and Epstein–Barr virus viral load to predict development of post-transplant lymphoproliferative disorder in paediatric liver transplant recipients.Clin Transplant 2006: 20: 389–393. © Blackwell Munksgaard, 2006

Objective: Currently there are no tests to accurately identify paediatric liver transplant patients at risk for post-transplant lymphoproliferative disorder (PTLD). Herein we describe the use of cytokine polymorphisms and real-time quantitative polymerase chain reaction (qPCR) Epstein–Barr virus (EBV) viral load to identify patients at risk for PTLD development.

Methods: Between 2001 and 2004, approximately 1047 patient samples were collected for qPCR for EBV in 59 patients. EBV viral load was reported in three groups: low EBV (<4 000 copies/μg DNA), high EBV/no PTLD (>4000 copies/μg DNA) and biopsy-proven PTLD. All 59 patients also had cytokine polymorphism genotyping performed for six cytokine polymorphisms (transforming growth factor (TGF)-β, tumor necrosis factor (TNF)-α, interleukins (IL)-6, IL-10, IL-2, and interferon (IFN)-γ) from DNA isolated from peripheral blood mononuclear cells. Positive predictive value (PPV) and negative predictive value (NPV) were calculated using qPCR and cytokine polymorphism results. Data are reported as a mean±standard error of the mean.

Results: There were 35 males and 24 females with a mean follow-up of 34.9 months. EBV viral load had a PPV and NPV of 29 and 95%, respectively. The low IFN-γ (A/A) polymorphism was found to be present in 4/6 PTLD patients (67%) and only 17/53 (33%) non-PTLD patients. When the low A/A IFN-γ polymorphism was combined with EBV viral load for prediction of PTLD, PPV and NPV were 57 and 93%, respectively.

Discussion: Use of cytokine genotyping in conjunction with qPCR for EBV viral load can significantly improve the predictive value of diagnostic tests for identification of patients at high risk for PTLD.