Abstract
Anti-CMV (cytomegalovirus) antibody titers are related to immune alterations and increased risk of mortality. To test whether they represent a marker of infection history, we analyzed the effect of viral reactivations on the production of specific antibodies in kidney transplant patients. We quantified CMV-DNAemia and antibody titers in 58 kidney transplant patients before transplantation and during a follow-up of 315 days (standard deviation, SD: 134.5 days). In order to calculate the intensity of the infection, we plotted the follow-up time of the infection on the x-axis and the number of DNA-CMV copies on the y-axis and calculated the area under the curve (CMV-AUC). The degree of T-lymphocyte differentiation was analyzed with flow cytometry, the cells were labelled with different monoclonal antibodies in order to distinguish their differentiation state, from naive T-cells to senescent T-cells. Peak viremia was significantly higher in patients experiencing a primary infection (VI) compared to patients experiencing viral reactivation (VR). Our data indicate that the overall CMV viral load over the course of a primary infection is significantly higher than in a reactivation of a previously established infection. Whereas patients who experienced an episode of CMV reactivation during the course of our observation showed increased levels of CMV-specific antibodies, patients who did not experience CMV reactivation (WVR) showed a drop in CMV antibody levels that corresponds to an overall drop in antibody levels, probably due to the continuing immunosuppression after the renal transplant. We found a positive correlation between the CMV viremia over the course of the infection or reactivation and the CMV-specific antibody titers in the examined patients. We also observed a positive correlation between anti-CMV titers and T-cell differentiation. In conclusion, our data show that anti-CMV antibody titers are related to the course of CMV infection in kidney transplant patients.
Highlights
After primary infection, CMV establishes chronic infections mainly in the myeloid cell compartment and endothelial cells
A strong induction of CMV-specific antibodies or a boost in the pre-existing CMV-specific antibody responses during virus reactivation is positively correlated with a strong CMV-AUC, when all patients are examined (Spearman test, rho = 0.670, p = 0.00000047) (Fig 3A), and when we focus only on patients who were seropositive at the time of transplantation (Spearman test, rho = 0.387, p = 0.038) (Fig 3B)
We found that virus replication is more aggressive in patients who are infected after transplantation, and that some patients did not produce detectable levels of anti-CMV antibodies
Summary
CMV establishes chronic infections mainly in the myeloid cell compartment and endothelial cells. Virus reactivation from latency can be caused by various situations, such as inflammation, infection, stress, or immunosuppression [1, 2]. The CMV-specific humoral and cellular immunity is not able to eliminate the virus, which periodically reactivates. Reactivations from latency are likely to occur in immunocompetent hosts, their functional immune system avoids the spread of the virus, and the infection is essentially asymptomatic. Transplant recipients receiving immunosuppressive therapy are at an increased risk of active CMV infection and disease. Despite the high efficacy of current antiviral preventive strategies, CMV infection is an important complication in patients receiving solid organ transplants, including kidney recipients [6,7,8]. Indirect effects have been associated with acute and chronic allograft rejection events, as well as new onset diabetes and accelerated coronary artery atherosclerosis in transplant patients [11]
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