Positive Cross-Match Living Donor Kidney Transplantation: Longer-Term Outcomes

Abstract

The incidence and treatment of both systemic and pulmonary human cytomegalovirus (HCMV) infection as well as HCMV-specific T-cell immune responses were investigated in 57 consecutive lung transplant recipients (LTR) by using as cutoffs for preemptive therapy: 300 000 DNA copies/mL whole blood for systemic infections and 100 000 DNA copies/mL bronchoalveolar lavage fluid for lung infections. Results showed that out of 29/57 LTR (50.9%) needing preemptive antiviral therapy, 15 (51.7%) reached the blood cutoff, 8 (27.6%) the pulmonary cutoff and 6 (20.7%) both the blood and the lung cutoff (3 simultaneously and 3 subsequently). Recovery of HCMV-specific T-cell immune responses was achieved much earlier for CD8 + than CD4 + T cells. However, protection from HCMV reactivation was conferred by the presence of both arms of the Tcell response. In two LTR reaching the pulmonary cutoff and not preemptively treated, a full HCMV-specific CD4 + and CD8 + T-cell response was associated with resolution of lung infection. Antirejection steroid therapy suppressed T-cell immune responses, thus facilitating HCMV reactivation. In conclusion, in LTR, monitoring HCMV infection in both blood and lungs, may improve preemptive therapy efficacy. In addition, monitoring the HCMV-specific T-cell immune response appears useful for predicting control of HCMV infection in the posttransplant period.

A Novel Non-Replication-Competent Cytomegalovirus Capsid Mutant Vaccine Strategy Is Effective in Reducing Congenital Infection

“…The pentameric complex is considered an important neutralizing target for HCMV on epithelial/endothelial cells and presumably for congenital infection, given the epithelial/endothelial structure of the placenta. The importance of the endocytic pathway in virus infection of cells is underscored by the fact that a gB subunit HCMV vaccine, despite generating a high-titer neutralizing immune response on fibroblasts, lacks an effective ability to neutralize infection of endothelial and epithelial cells compared to convalescent-phase sera (41,(52)(53)(54)(55). With RhCMV, the pentameric complex has been demonstrated to be an important pathogenicity factor as well as a neutralizing target antigen (100,101).…”

“…This is despite high antibody titers which are effective in neutralizing virus on fibroblasts (41,52). Importantly, separate studies of serum from gB-vaccinated individuals showed that it was less effective at neutralizing virus infection on endothelial and epithelial cells, in comparison to convalescent-phase sera from HCMV-infected individuals (53)(54)(55). This demonstrated the importance of other viral neutralizing target antigens for infection on these cell types.…”

Detection of Human Herpesvirus-7 DNA in Bronchoalveolar Lavage

“…This level was chosen taking into account that HHV-7, similarly to HCMV, latently persists in lung, and that a HCMV load 1 100,000 GEq/ml BAL is suggested as being associated with organ disease in solid organ transplant recipients and a cutoff for preemptive therapy in lung transplant recipients [18] . Viral load was 1 100,000 GEq/ ml BAL in 6/22 (27.3%) transplant recipients and 4/18 (22.2%) non-transplant patients (p = n.s.).…”

CMV management in lung transplant recipients

“…CMV management after transplantation is based on 2 different strategies: antiviral prophylaxis, consisting in therapy irrespective of clinical and specimens' status, and pre-emptive therapy, consisting of the administration of antiviral agents after reaching a predetermined cut-off (71) in CMV polymerase chain reaction (PCR) copies on whole blood, but before the development of clinical symptoms. In lung transplant (LT) recipients, the practice of surveillance bronchoscopies with transbronchial biopsy (TBB) and bronchoalveolar lavage (BAL) allows for subclinical evaluation of rejection and organ infections.…”