Use of antibodies neutralizing epithelial cell infection to diagnose patients at risk for CMV Disease after transplantation.

OBJECTIVES

Although a CMV-specific T-cell response is associated with reduced risk for infection after transplantation, some patients still develop CMV disease. Thus, the characterization of additional parameters of the CMV-specific immune response that correlate with the control of CMV infection and disease and their use in defining thresholds that can be applied to clinical practice is of interest.

METHODS

In a cohort of high risk solid organ transplant recipients we characterized CMV-specific T-cell responses using intracellular cytokine staining upon stimulation with pp65 and IE-1 peptides, and levels of CMV-specific antibodies neutralizing infection in fibroblast (MRC-5) and epithelial (ARPE-19) cells using microneutralization assays.

RESULTS

Although patients with a positive (≥0.25%CD8(+)CD69(+)IFN-γ+) T-cell response were 6.4 fold more protected (OR 6.4, 95% CI 1.6-25.3; p < 0.001) from CMV infection than patients without a response, 2 (4.2%) patients developed disease. We defined a cut-off titer for epithelial cell neutralizing antibodies of ≥480 that correlated with disease protection. Thus, patients with a CMV-specific T-cell response and titers ≥480 were 14.2 fold more protected from CMV infection (OR 14.2, 95% CI 5-40.2; p < 0.001) and had no episodes of CMV disease.

CONCLUSIONS

Our results indicate that antibodies neutralizing epithelial cell infection may have an important role in long-term protection. Quantification of antibodies neutralizing epithelial cells, in addition to the T-cell response, may be useful for identifying patients with lower risk for CMV disease.