Comparison of Three Cellular Assays to Predict the Course of CMV Infection in Liver Transplant Recipients

Smaranda Gliga,Melanie Fiedler,Theresa Dornieden,Kerstin Herzer,Kerstin Herzer,Anne Achterfeld,Monika Lindemann,Andreas Paul,Peter A Horn

doi:10.3390/vaccines9020088

Smaranda Gliga, Melanie Fiedler + Show 7 more

Open Access

https://doi.org/10.3390/vaccines9020088

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Abstract

To estimate protection from cytomegalovirus (CMV) replication after solid organ transplantation, CMV serology has been considered insufficient and thus CMV immunity is increasingly assessed by cellular in vitro methods. We compared two commercially available IFN-γ ELISpot assays (T-Track CMV and T-SPOT.CMV) and an IFN-γ ELISA (QuantiFERON-CMV). Currently, there is no study comparing these three assays. The assays were performed in 56 liver transplant recipients at the end of antiviral prophylaxis and one month thereafter. In CMV high- or intermediate-risk patients the two ELISpot assays showed significant correlation (p < 0.0001, r > 0.6) but the correlation of the ELISpot assays with QuantiFERON-CMV was weaker. Results of both ELISpot assays were similarly predictive of protection from CMV-DNAemia ≥500 copies/mL [CMV pp65 T-SPOT.CMV at the end of prophylaxis: area under curve (AUC) = 0.744, cut-off 142 spot forming units (SFU), sensitivity set to 100%, specificity 46%; CMV IE-1 T-Track CMV at month 1: AUC = 0.762, cut-off 3.5 SFU, sensitivity set to 100%, specificity 59%]. The QuantiFERON-CMV assay was inferior, reaching a specificity of 23% when setting the sensitivity to 100%. In conclusion, both CMV-specific ELISpot assays appear suitable to assess protection from CMV infection/reactivation in liver transplant recipients.

Highlights

The seroprevalence of the human cytomegalovirus (CMV), a DNA virus of the herpes family, ranges between 45 and 100% in the general adult population [1]
ELISpot responses to the two antigens, immediate early antigen-1 (IE-1) and pp65, showed moderate to strong correlations (r = 0.609 to r = 0.706) (Table 2a). Results of both ELISpot assays showed weak to moderate correlations with results of the QuantiFERON-CMV assay (Table 2b); correlation with CMV IE-1-specific ELISpot assays was weak (r = 0.217 to r = 0.387) and correlation with CMV pp65-specific ELISpot assays was moderate (r = 0.551 to r = 0.647)
In one patient (ID 1) both ELISpot assays and the QuantiFERONCMV assay were positive at the same time CMV-DNAemia was detected

Summary

Introduction

The seroprevalence of the human cytomegalovirus (CMV), a DNA virus of the herpes family, ranges between 45 and 100% in the general adult population [1]. In transplant recipients CMV infection or reactivation can lead to fever, hepatitis, colitis, interstitial pneumonitis, encephalitis, vasculopathy or allograft rejection [3,4,5]. In these immunocompromised individuals CMV infection/reactivation results in significant morbidity and treatment costs. It can even be life-threatening [3]. In liver transplant recipients it was associated with a higher rate of accelerated hepatitis C recurrence, hepatic artery thrombosis and cholangitis [6,7]

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