Evaluation of virus-specific cellular immune response in transplant patients

Abstract

Virus-specific immune responses have a major impact on the outcome of the infection. Viral agents that are characterized by latency, such as herpesviruses and polyomaviruses, require a continuous immune control to reduce the extent of viral reactivation, as viral clearance cannot be accomplished, independently from the anti-viral treatment. In transplant patients, morbidity and mortality related to viral infections are significantly increased. In fact, the key steps of activation of T-cells are major target for anti-rejection immunosuppressive therapy and anti-viral immune response may be altered when infected cells and cellular effectors of immune response coexist in a transplanted organ. The role of cellular immune response in controlling viral replication and the main methods employed for its evaluation will be discussed. In particular, the main features, including both advantages and limitations, of available assays, including intracellular cytokine staining, major histocompatibility complex -multimer-based assays, Elispot assay, and QuantiFERON test, will be described. The potential applications of these assays in the transplant context will be discussed, particularly in relation to cytomegalovirus and polyomavirus BK infection. The relevance of introducing viro-immunological monitoring, beside virological monitoring, in order to identify the risk profile for viral infections in the transplant patients will allows for define a patient-tailored clinical management, particular in terms of modulation of immunosuppressive therapy and anti-viral administration.

Clinical immune‐monitoring strategies for predicting infection risk in solid organ transplantation

“…In parallel to the above attempts to characterize CMV-specific immunity, some efforts have been focused on other relevant viral agents for the SOT population, mainly EBV and BKPyV. 123 EBV possesses the capacity to establish lifelong latency within the B-cell compartment following primary infection. 124 The control of latent EBV infection in healthy individuals depends largely on the status of cell-mediated immune response.…”

Persistently high-level polyomavirus BK replication in the absence of renal function abnormalities in a kidney transplant recipient

“…Elispot assay revealed the lack of polyomavirus BK-specific T-cell response, thus suggesting the failure of patient's immune-surveillance (5,6). According to PVAN definition criteria, in this patient, a presumptive diagnosis of PVAN could be made, as evidenced by a prolonged (>3 weeks) BKV viremia >10 4 copies/mL (2,9).…”

“…In the following months up to +24, BKV viremia increased and reached levels almost persistently >10 4 copies/mL serum with peak values >5x10 6 ; viruria was persistently >5x10 6 copies/mL throughout the whole period. Nevertheless, serum creatinine levels were stable with a mean value of 1.2 mg/dL.…”