Abstract: FR-OR085

Increased Expression of the Co-Inhibitors PD-1 and BTLA on CMV-Specific T-Cells Is Associated with Symptomatic CMV Infection in Renal Transplant Patients

Session Information

Category: Transplantation

  • 1702 Transplantation: Clinical and Translational

Authors

  • Wilde, Benjamin, University Duisburg-Essen, University Hospital Essen, Essen, Germany
  • Dolff, Sebastian, University Duisburg-Essen, University Hospital Essen, Essen, Germany
  • Witzke, Oliver, University Duisburg-Essen, Essen, Germany
Background

Cytomegalovirus (CMV) infections occur frequently in renal transplant patients due to immunosuppressive therapy inhibiting CMV-specific T-cell immunity. Prophylaxis with antiviral agents or pre-emptive strategies to monitor viral load and then treat do not prevent infections sufficiently. It was the aim of this study to investigate if the expression of inhibitory molecules on CMV specific T-cells is associated with the clinical course of renal transplant patients.

Methods

30 renal transplant patients were recruited. Peripheral blood was sampled and stimulated with CMV lysate, SEB or control serum. The coinhibitors PD-1 and BTLA were determined on CMV-specific T-cells. Clinical data was collected retrospectively from patient files. Symptomatic CMV infection was defined as CMV syndrome or tissue invasive disease. Asymptomatic CMV infection was defined as detectable CMV replication in peripheral blood and absence of signs indicating CMV syndrome/tissue invasive disease.

Results

Two renal transplant patients were at low risk for CMV infection according to donor /recipient CMV IgG sero-status at the time of transplantation (D neg / R neg). Seven patients had a high risk according to sero-status (D pos /R neg) and the remaining 21 patients were confined to the intermediate risk group (D pos /R pos or D neg / R pos). Patients with low risk were excluded for further analysis. PD-1 expression was significantly enhanced on CMV-specific CD3+ T-cells in patients with a history of symptomatic CMV infection (n=6) as compared to patients with asymptomatic CMV (n=14) infection (CD3+CD154+: % of PD-1+ 63.8 ±16.0% vs. 37.2 ±19.4%, p=0.006). Likewise, expression of BTLA on CMV-specific T-cells was significantly increased in patients with symptomatic versus asymptomatic CMV infection (CD3+CD154+: % of BTLA+ 89.3 ±9.5% vs. 66.0 ±22.0%, p=0.003).

Conclusion

Patients with symptomatic CMV infection had enhanced expression of PD-1/BTLA on virus-specific T-cells. The coinhibitors PD-1/BTLA usually promote T-cell suppression. Therefore, increased expression of PD-1/BTLA on CMV-specific T-cells may compromise viral control and could serve as biomarker to stratify patients at risk.