The Immune Response to Epstein Barr Virus and Implications for Posttransplant Lymphoproliferative Disorder

Abstract

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication in organ transplant recipients and is most often associated with the Epstein Barr virus (EBV). EBV is a common gammaherpes virus with tropism for B lymphocytes and infection in immunocompetent individuals is typically asymptomatic and benign. However, infection in immunocompromised or immunosuppressed individuals can result in malignant B cell lymphoproliferations such as PTLD. EBV+ PTLD can arise following primary EBV infection, or because of reactivation of a prior infection, and represents a leading malignancy in the transplant population. The incidence of EBV+ PTLD is variable depending on the organ transplanted and whether the recipient has preexisting immunity to EBV but can be as high as 20%. It is generally accepted that impaired immune function due to immunosuppression is a primary cause of EBV+ PTLD. In this overview, we review the EBV life cycle and discuss our current understanding of the immune response to EBV in healthy, immunocompetent individuals, in transplant recipients, and in PTLD patients. We review the strategies that EBV utilizes to subvert and evade host immunity and discuss the implications for the development of EBV+ PTLD.

Management of post‐transplant lymphoproliferative disorders

“…Expressed viral latency proteins can drive naïve B cells through a germinal centre reaction and into a post‐germinal centre memory B cell, in which EBV is able to persist quiescently in the peripheral blood and reticuloendothelial system in the absence of expressed viral latency proteins (Shannon‐Lowe et al , ). The full repertoire of expressed EBV latency proteins are exquisitely immunogenic and under normal conditions in an immunocompetent host trigger a vigorous immune response which controls the infection (Martinez & Krams, ).…”

Evaluation of the Abbott RealTime quantitative CMV and EBV assays using the maxCycle protocol in a laboratory automation context

“…They are both able to reactivate frequently throughout the lifespan and to disseminate within the infected body. In immunocompromised patients, CMV reactivation can lead to serious complications like allograft rejection (Dioverti and Razonable, 2016) while EBV infection is associate to malignant B cell lymphoproliferations (Martinez and Krams, 2017). According to international guidelines, the use of quantitative EBV and CMV PCR in blood is indicated in all hematopoietic stem cell transplant (HSCT) or solid organ transplant (SOT) recipients to allow early initiation of antiviral therapies and also for their monitoring (Gulley and Tang, 2010;Heemann et al, 2011;Kotton et al, 2013;Torre-Cisneros et al, 2016).…”

The value of EBV DNA in early detection of post-transplant lymphoproliferative disorders among solid organ and hematopoietic stem cell transplant recipients

“…Clinically and histologically, PTLD consists of a heterogeneous spectrum of disorders ranging from benign proliferation of B lymphocytes to fulminant lymphoma, where the latter can resemble those seen in immunocompetent patients [6][7][8]. Furthermore, PTLD is associated with Epstein Barr Virus (EBV) in the majority of the cases [1,8].…”