Evaluation of QuantiFERON-CMV Assay for Detection of CMV-Specifi c Cellular Immunity in Immunocompromised Patients.

Abstract

Intracellular cytokine staining (ICS) using flow-cytometry has been characterized as a correlate for serology and for monitoring of infectious complications in CMV-positive individuals in a pre-emptive setting. In contrast, knowledge on the performance characteristics of the QFT-CMV assay in these settings is limited. Therefore, we performed a comparative analysis of QFT-CMV with serology and ICS in a cross-sectional setting in 34 controls, 71 hemodialysis (HD), 38 renal (RTx) and 23 lung transplant patients (LTx). Twelve of the Tx patients had a history of CMV primary infection. In addition, 30 seropositive RTx patients were prospectively analyzed before and during the first four months after transplantation and results were stratified in relation to the development of viremia after transplantation. Indeterminate results were observed only in QFT-CMV assay (2.4%). CMV-specific immunity was detected in 65.7% of QFT-CMV and in 72.9% of ICS samples, respectively. Agreement with serology was almost perfect for ICS (K=0.96), and substantial for QFT-CMV (K=0.72). Agreement between QFT-CMV and ICS was substantial (K=0.76). Quantitative analysis of CMV-seropositive individuals revealed no significant differences in CMV-specific IFNγ production (QFT-CMV) or T-cell frequencies (ICS) between the different groups (p=0.294 and p=0.041 with all p>0.05 in post tests respectively). All Tx patients with a history of primary infection developed CMV-specific antibodies and T cells although QFT-CMV failed in one patient. In longitudinal analyses, a significant decrease in IFNγ levels was observed during the first two months after transplantation (from median(IQR) 8.32(16.32) U/ml to 3.12(8.75) U/ml). Interestingly, when stratified according to viremia, this decrease was only significant in patients with subsequent viremia. Conclusion: The QFT-CMV is an easily applicable assay for monitoring cellular immunity towards CMV with a substantial agreement with serology and ICS. T-cell reactivity decreases early after transplantation in temporal association with high levels of immunosuppression. As the extent of this decrease detected with QFT-CMV seems to be associated with virus reactivation, the assay may have potential to serve for monitoring of infectious complications among seropositive Tx patients. DISCLOSURES:Sester, U.: Stockholder, Red flag diagnostics. Sester, M.: Stockholder, Red Flag Diagnostics.