Immune-based monitoring for cytomegalovirus infection in solid organ transplantation: is it ready for clinical primetime?

Abstract

The impact of CMV infection and disease in solid organ transplant (SOT) recipients continues despite remarkable improvements in its prevention and management with antiviral drugs. Studies that have investigated the host immune response to CMV have paved way for the development of novel immune-based assays that are anticipated to complement the current antiviral-based strategies for CMV management after transplantation. In this article, we review the emerging data on the clinical application of innovative CMV-specific T-cell assays, including their role in risk-stratification, prognostication, prevention and treatment of CMV infection and disease in SOT recipients.

Keywords::

• clinical disease
• CMV
• immunity
• relapse
• risk factors
• transplantation

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• More than 50% of solid organ transplant (SOT) recipients will experience CMV replication and 10–50% of them will develop symptomatic disease, in the absence of antiviral prophylaxis or preemptive therapy.

• Knowledge of CMV-specific cellular immune status in a post-transplant recipient can potentially be used to personalize CMV preventive strategy and this could reduce drug-related negative effects (cost of drug, drug resistance and adverse effects).

• Several platforms are used to detect CMV-specific T-cell immunity, including intracellular cytokine staining and cytokine flow cytometry, ELISpot and IFN-γ release assays.

• CMV-specific T-cell immunity, as measured by cytokine flow cytometry, ELISpot and IFN-γ release assays, has been correlated with the risk of CMV viremia and disease in SOT recipients. Among the assays studied to date, the detection of IFN-γ release by QuantiFERON-CMV is closest to clinical application.

• The lack of IFN-γ release from CD8⁺ T cells in response to a collection of CMV peptides has been significantly associated with subsequent risk of CMV disease in SOT recipients. The level of IFN-γ release during CMV stimulation ex vivo has been observed to discriminate the need for antiviral therapy in SOT recipients with low-level subclinical viremia.

• Several applications of CMV-specific T-cell assays that need to be studied are: its role in guiding the need for prophylaxis or preemptive therapy, its role as a guide for when to discontinue antiviral prophylaxis, its role as a guide for when to safely discontinue antiviral treatment in SOT recipients with CMV disease and its role in predicting drug resistance and the risk of clinical and virologic relapse.