Assessment of cytomegalovirus specific T-cell immunity by the interferon gamma release assay in transplant recipients

Abstract

CMV infection is an important complication of transplant recipients, especially in the context of hematopoietic stem cells (HSCT) and lung transplantation. The use of prophylaxis after lung transplantation and the pre-emptive therapy with ganciclovir (GCV), ie, the early introduction of GCV based on positivation of rapid diagnostic techniques (detection of pp65 antigenemia or PCR), significantly reduced the morbidity and mortality related to this agent. More recently, the increase in transplant complexity, translated by the use of new immunosuppressive drugs in the prophylaxis and control of rejection or graft versus host disease (GVHD), and the use of alternative donors (HSCT with unrelated donors) has triggered changes in the reactivation patterns of certain infectious agents, including CMV. Prolonged lymphopenia is one of the main risk factors for CMV reactivation. This in turn, while defining the risk for the development of CMV disease and the need for early introduction of antiviral, is a strong stimulus for the reconstitution of CMV-specific immunity. The reconstitution of the CMV-specific response of CD4 and CD8 cells (immunity to CMV) enable the control of infection even in the absence of antiviral, while the delay in this response favors the recurrence of reactivation episodes and / or prolonged viremias in which antiviral use is indispensable. Prolonged viremias are often misinterpreted as GCV resistance, especially in patients on prophylactic use of ganciclovir. Until recently, only sophisticated in-house interferon gamma release assays (IGRAs) were available for the evaluation of CMV immunity. Currently, an enzyme immunoassay (QuantiFERON-CMV, Qiagen, USA) is commercially available. The assay doses the amount of IFN-gamma produced by host CMV-specific T lymphocytes in response to immunodominant peptides from CMV. Thus, this assay may represent an advance in the management of CMV infections in these populations. In the present study, we will be evaluate the dynamics of immune reconstitution of CMV-specific T cells in a population of allogeneic HSCT and lung recipients, the variables associated with the reconstitution of CMV-immunity, and the usefulness of the QuantiFERON-CMV in identifying risk groups for recurrent episodes of CMV reactivation and disease. (AU)