Control of CMV replication depends primarily on anti-CMV T lymphocyte activity. However, the functional T-cell responses to CMV in immunosuppressed solid organ transplant recipients are not well understood. In this study we employed cytokine flowcytometry (CFC) using pooled CMV peptides and viral lysates to detect CMV-specific T-cell responses in 17 healthy controls, 33 stable renal transplant recipients (Tx recipients) and 6 transplant recipients with active CMV infection (CMV(+)). We found that pooled peptides and lysates provide optimal detection of IFNc production in anti-CMV CD8 + and CD4 + T cells, respectively. In both healthy controls and Tx recipients, CMV-specific T-cell levels strongly correlated with serostatus. Seropositive Tx recipients have significantly higher levels of CMV-specific CD8 + T-cell responses compared to healthy controls, which may signify an effort to control enhanced viral replication in immunosuppressed Tx recipients. In some individuals, absence of anti-CMV T-cell response may correlate with lack of viral clearance by ganciclovir therapy, even when CMV isolates are not ganciclovir resistant. Thus, monitoring cellular immunity with CFC along with viral load by PCR merits further exploration for identification of patients at the risk of developing CMV disease, tailoring prophylactic and therapeutic decisions and preventing complications.
In conclusion, high plasma BK-positivity (>10) is significantly associated with BK nephropathy. Plasma BK-positivity is highly associated with co-infection of CMV, suggesting possible risk factors for one another. Therefore, detection of either infection strongly suggests the need to monitor for the other. This strategy may lead to the prevention of virus-induced complications by preemptive antiviral therapy in renal allografts.
Congenital cytomegalovirus (CMV) infection occurs in approximately 1% of newborns and is the leading infectious cause of congenital birth defects. Female renal allograft recipients who develop CMV infection during pregnancy are at risk for both graft dysfunction and fetal morbidity. DNA-based analysis of amniotic fluid (AF) from at-risk pregnancies has been suggested as an adjunct/substitute for traditional culture. We have shown that CMV-polymerase chain reaction of AF is a useful diagnostic test for congenital CMV infection. Using this test we diagnosed CMV infection in the fetus of a 30-year-old renal transplant recipient. As termination was not an option for the family, the patient was extensively counseled and treated with oral ganciclovir. This resulted in clearance of the virus from the AF and the delivery of a healthy newborn girl, free of CMV disease. This is the first reported case to our knowledge of successful use of maternal ganciclovir to treat intrauterine CMV infection in a pregnant renal transplant recipient.
Higher BKV levels in plasma are associated with renal dysfunction. Kidney transplant recipients are at high risk compared with recipients of isolated heart or liver allografts, for development of BKV nephropathy.
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