Levels of anti-CMV antibodies are modulated by the frequency and intensity of virus reactivations in kidney transplant patients

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.

Current characteristics and outcomes of Cytomegalovirus Reactivation in kidney transplant seropositive recipients in the era of prophylaxis treatment. Lesson from single Moroccan center experience

“…Despite prophylaxis, 63% of first episodes reactivation was observed in this group. This finding was in accordance with data of recent literature, 43 to 61.9% CMV seropositive transplant patients had experienced virus reactivation or re-infection by detection of viral DNA [18, 29]. One study [30] demonstrated that transplanted organ of seropositive donor was associated with 49% infection rates in the recipients with lack of prophylactic treatment.…”

“…However, the active CMV replication is still occurred in the D+/R+ population over the first three months of prophylaxis [17,18], and associated with CMV viraemia or with late-onset disease [19][20][21]. Furthermore, CMV recurrence infections can be developed after the first episode of reactivation in this group [22][23][24].…”

“…Therefore, antiviral prophylaxis is usually recommended for a short period with three months of treatment by recent consensus guidelines [16]. However, the active CMV replication is still occurred in the D+/R+ population over the first three months of prophylaxis [17,18], and associated with CMV viraemia or with late-onset disease [19–21]. Furthermore, CMV recurrence infections can be developed after the first episode of reactivation in this group [22– 24].…”

Cytomegalovirus seroprevalence, recurrence, and antibody levels

“…This suggests the immunotoxicity of lead is not strong enough to tip the balance towards recurrence, but could slightly impair the immune system’s capacity to contain the virus quickly when recurrences occur in young adulthood. 32 …”

“… 60 Since low socioeconomic status is related to greater cadmium and lead exposures as well as to greater CMV exposure (for instance, from daycare attendance, number of sexual partners, and crowded housing conditions), 48 , 56 we would expect any residual confounding to result in overestimated associations of blood metal concentrations with CMV seropositivity and antibody levels. Finally, while elevations in CMV-specific IgG levels might correlate with the length or frequency of CMV recurrences in immunosuppressed patients, 32 their significance in immunocompetent individuals is unclear. 61 …”