Monoclonal gammopathy of undetermined significance (MGUS) is associated with an increased frequency of Epstein-Barr Virus (EBV) latently infected B lymphocytes in long-term renal transplant patients

Abstract

Monoclonal gammopathy of undetermined significance (MGUS) is a common phenomenon in kidney transplant patients that might be a prestage of posttransplant lymphoproliferative disease (PTLD). Because the role of Epstein-Barr virus (EBV) for PTLD development is well established, we wondered about the association between EBV and MGUS. Thus, B-cells from kidney transplant patients (25 with and 100 without MGUS) and from 100 healthy controls were analyzed for EBV latent (EBER1) and lytic (EA, VCA) gene expression by RT-nested PCR. The EBV load was measured by real-time PCR. A significantly higher EBV load and expression of the nonimmunogenic latency associated EBER 1 gene was observed in patients with MGUS compared to both control groups ( P < .001). In addition, a rare detection of the highly immunogenic lytic transcripts demonstrated a linkage between latency-associated EBV infection and MGUS in transplant patients. This pattern was similar to EBV-associated B-cell lymphomas in nonimmunosuppressed patients. It contrasted with PTLD patients who express higher EBV loads and both lytic and latent EBV transcripts. These data suggest that transplant patients with MGUS demonstrate a more sufficient control of EBV-infected B-cells. Nevertheless, EBV monitoring should be performed in patients with EBV-associated MGUS for early detection of later PTLD.