Epstein-Barr virus surveillance after renal transplantation

At least 1% of organ transplant recipients develop Epstein-Barr virus-positive, often fatal lymphomas. EBV-positive cells accumulating in some organ transplant recipients were suggested to predict EBV+ lymphoma risk but no prospective study has been reported. We used the polymerase chain reaction (PCR) to detect EBV genomic sequences in successive blood samples of 60 kidney recipients before and up to 11 years after renal transplantation. Xenotransplantation of EBV-positive patient and -negative control samples into mice with severe combined immunodeficiency (SCID) was used to assess the tumor risk inherent in these samples. Despite single EBV+ cell detection sensitivity, none of the control samples was positive for EBV genomic sequences. In nearly 2/3 of patients EBV genomic DNA was detectable 3-6 months after transplantation for about 3 months. No patient developed lymphoma. Lymphocytes from 8 EBV-genome positive patients and 10 healthy donors were engrafted into 38 SCID mice. Human B cell lymphoma developed in 75% of the control grafts within about 3 months. In striking contrast, none of the patient grafts developed lymphoma despite the large numbers of EBV+ cells initially transplanted. Patient lymphocyte grafts were resistant to injection of live EBV, while in control lymphocyte grafts this caused lymphoma development within 3 weeks. We conclude that a 100-1000-fold expansion of circulating EBV+ B cell pools occurs frequently after organ transplantation and that it is balanced by effective EBV immunosurveillant functions resistant to immunosuppression. The mere detection of EBV genomic material was not predictive of lymphoma development.