The protection from CMV infection in solid organ transplants is highly dependent on CMV T-cell specific immunity and type of organ transplant
Alda Saldan1, Carlo Mengoli1, Dino Sgarabotto1, Marianna Alessi1, Antonio Gambino1, Luciana Bonfante1, Patrizia Burra1, Francesco Marchini1, Patrizia Boccagni1, Giuseppe Toscano1, Giuseppe Feltrin1, Cristina Silvestre1, Francesco P Russo1, Lucrezia Furian1, Monica Loy1, Luisa Barzon1, Giacomo Sturniolo1, Umberto Cillo1, Paolo Rigotti1, Federico Rea1, Davide Abate1.
1Department of Molecular Medicine, University of Padova, Padova, Italy
Introduction: The CMV specific immune recovery is known to control viral infection and disease. The CMV specific cell-mediated immunity (CMI) and CMV specific humoral immune response (IgG titer and IgG avidity) was explored as candidate biomarker predictive of CMV infection.
Methods: 653 observations from 297 SOT including 103 kidney (K), 60 liver (L), 47 heart (H), 87 Lung (Lu) transplants. The follow-up was 0-400 days after transplant. The following parameters were examined: 1) CMV serostatus before transplant 2) CMV IgG titer 3) CMV IgG avidity 4) CMV-ELISPOT 5) primary (D+/R-) or non-primary (D±/R+) CMV infection 6) CMV viremia. Data were statistically analyzed using ANOVA and linear regression analysis and spline model.
Results: The main findings of the study are: 1) CMV IgG titers and avidity are not predictive biomarker for CMV infection. The CMV IgG titer and IgG avidity levels are comparable either in infected and non-infected patients. 2) CMV viral load is statistically different between infected D±/R+ and D+/R-. The viral load in infected D+/R- is 1 Log higher compared to D±/R+ (10^5 vs 10^4 respectively) 4) The CMV immune reconstitution is more rapid and efficient in D±/R+ compared to D+/R- 5) D±/R+ and D+/R- Kidney and Lung transplants display a statistically significant lower CMI compared to heart and liver transplants; 6) Kidney and Lung transplants display a similar pattern of immune recovery 7) The CMV cell mediated immunity biomarker is predictive of infection in all organs with exception of lung transplants.
Conclusions: The study shows a marginal role of humoral immunity in controlling CMV infection. The pattern of CMI immune recovery is highly dependent upon pre-transplant CMV serostatus, type of organ transplant and immunosuppression therapy. High levels of CMV specific cell-mediated immunity correlate with a reduced CMV infection risk in heart, kidney and liver transplants. A different scenario emerged in lung transplants: high levels of circulating CMV specific T-cells can be found in lung transplants but cannot prevent CMV infection and clear the virus. In this view the lung may be considered a "sanctuary site" for CMV replication.
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