CMV-specific T-cell immunity in solid organ transplant recipients at low risk of CMV infection. Chronology and applicability in preemptive therapy

Kinetic of the CMV‐specific T‐cell immune response and CMV infection in CMV‐seropositive kidney transplant recipients receiving rabbit anti‐thymocyte globulin induction therapy: A pilot study

“…In a recent study performed in our group in SOT CMV‐seropositive recipients, without rATG induction, who received preemptive therapy for CMV infection, 90.9% patients with positive pretransplant immune response achieved a CMV‐specific cellular immune response 4 weeks after transplantation. In addition, positive immunity was predictive of protection for developing high viremia and treatment requirement . Although other studies have also demonstrated that patients with positive pretransplant CMV cellular immune response had lower risk for CMV infection after transplantation than patients with negative pretransplant response using QuantiFERON ® ‐CMV assay or enzyme‐linked immunospot (Elispot) assay, this is the first study analyzing the CMV‐specific T‐cell immune response kinetic using intracellular cytokine staining before and after transplantation in patients who receive rATG induction and CMV prophylaxis.…”

“…The percentages of activated CD4 + and CD8 + cells that express CD69/IFN‐γ and CD69/IL‐2 were normalized to the negative control. Samples were considered positive for CMV‐specific T‐cell response when the percentage of activated CD4 + CD69 + INF‐γ+ and CD8 + CD69 + T cells was ≥0.25% …”

Going beyond serology for stratifying the risk of CMV infection in transplant recipients

“…24 which is usually considered as the reference technique to quantify the CMV-specific cell-mediated immunity (CMI), 25 we found that 77.6% of R + patients lack detectable pretransplant T-cell response. 26 In addition, up to 20% of R + SOT recipients, conventionally considered at intermediate risk, will still develop episodes of CMV infection and disease after transplantation. 27,28 While lower pretransplant CMV IgG antibody titers have been significantly associated with CMV infection after liver transplantation 29 and the IgG serostatus was predictive of subsequent CMV disease between month 6 and 12 (with incidence rates of 1.3% and 10.0% in R + and R − groups, respectively), 30 The negative impact on overall survival of receiving an allograft from a CMV-seronegative donor was recently confirmed and appeared to be directly related to CMV-associated outcomes, namely increased incidence of recurrent episodes of active CMV infection (in particular those requiring the initiation of antiviral therapy) and late end-organ disease.…”

“…Using an ELISPOT assay, Ritta et al observed similar results, and more recently, Schachtner et al reported lack of CMV‐specific T‐cells in 20% of R + kidney transplant recipients. Using intracellular cytokine staining, which is usually considered as the reference technique to quantify the CMV‐specific cell‐mediated immunity (CMI), we found that 77.6% of R + patients lack detectable pretransplant T‐cell response . In addition, up to 20% of R + SOT recipients, conventionally considered at intermediate risk, will still develop episodes of CMV infection and disease after transplantation .…”

“…Ritta et al and Bestard et al found that having low pretransplant CMV‐specific T‐cell responses was associated with a higher risk of post‐transplant CMV replication . López‐Oliva et al reported that low pretransplant CMV‐specific CD8 + T‐cell counts predicted the development of CMV infection with 100% specificity and 85.7% sensitivity, while Mena‐Romo et al found that patients were more prone to suffer from CMV disease in the absence of detectable pretransplant CMI . More recently, the quantification of pretransplant CMV‐specific T‐cells directed against immediate early (IE)‐1, and/or pp65 antigens has been proven to be useful for the identification of R + kidney transplant recipients at increased risk for CMV‐disease …”