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. 2024 Jun 28:15:1414830.
doi: 10.3389/fimmu.2024.1414830. eCollection 2024.

Cellular immunity against cytomegalovirus and risk of infection after kidney transplantation

Kjersti B Blom  1   2   3   4 , Grete B Kro  5 , Karsten Midtvedt  6 , Trond G Jenssen  4   6 , Anna Varberg Reisæter  6 , Hallvor Rollag  4 , Anders Hartmann  6 , Solbjørg Sagedal  1 , Ivar Sjaastad  2   3 , Garth Tylden  7 , Gro Njølstad  8 , Einar Nilsen  9 , Jon A Birkeland #  1 , Anders Åsberg #  6   10   11
Affiliations

Cellular immunity against cytomegalovirus and risk of infection after kidney transplantation

Kjersti B Blom et al. Front Immunol. .

Abstract

Introduction: Cytomegalovirus (CMV) infection remains a challenge following kidney transplantation (KTx). Currently, CMV-IgG serostatus at transplantation is used to individualize CMV preventive strategies. We assessed the clinical utility of CMV-IGRA for predicting CMV infection following KTx.

Methods: We performed a nationwide prospective cohort study from August 2016 until December 2022. Data from all adult KTx recipients in Norway, n=1,546 (R+; n=1,157, D+/R-; n=260, D-/R-; 129), were included with a total of 3,556 CMV-IGRA analyses (1,375 at KTx, 1,188 at eight weeks, 993 one-year after KTx) and 35,782 CMV DNAemia analyses.

Results: In R+ recipients CMV-IGRA status, measured at any of the time-points, could not identify any differential risk of later CMV infection. D+/R- recipients remaining CMV-IGRA negative 1-year after transplantation (regardless of positive CMV DNAemia and/or CMV IgG status at that time) had increased risk of developing later CMV infection compared to D+/R- recipients who had become CMV-IGRA positive (14% vs. 2%, p=0.01).

Conclusion: Knowledge of pre-transplant CMV-IGRA status did not provide additional information to CMV-IgG serostatus that could improve current post-transplant CMV treatment algorithms. However, D+/R- recipients with a persisting negative CMV-IGRA one-year after transplantation remained at increased risk of experiencing later CMV infection. Therefore we advocate post-transplant CMV-IGRA monitoring in these patients.

Keywords: CMI (cell mediated immunity); CMV-IGRA; cytomegalovirus (CMV); cytomegalovirus infection; kidney transplansplantation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow-chart depicting exclusion of ineligible kidney transplant recipients from the study.
Figure 2
Figure 2
The figure shows Kaplan-Meier analysis of freedom from CMV infection after transplantation in CMV seropositive kidney recipients (abbreviation R+). The curves show patients with positive or negative CMV-IGRA status at time of transplantation in (A), IGRA status at 8 weeks in (B) and at 1 year in (C). Patients were subjected to weekly CMV DNAemia monitoring during the first two months, monthly up to one year and on clinical indication thereafter. Monitoring of CMV were lacking in nine, three and four patients respectively in (A–C).
Figure 3
Figure 3
Box plot showing CMV-IGRA values among all CMV seropositive kidney recipients before transplantation, eight weeks post-transplantation and one year post-transplantation.
Figure 4
Figure 4
Kaplan-Meier analysis of freedom from CMV infection after eight weeks posttransplant. Patients converting from positive to negative CMV-IGRA status eight weeks after transplantation are compared to those maintaining positive CMV-IGRA status in CMV seropositive kidney recipients. All patients were subjected to monthly CMV DNAemia monitoring up to one year and on clinical indication thereafter.
Figure 5
Figure 5
Box plot showing CMV-IGRA values among all CMV negative kidney recipients who received a CMV positive kidney (D+/R-) before transplantation, eight weeks post-transplantation and one year post-transplantation.
Figure 6
Figure 6
The figure shows Kaplan-Meier analyses of freedom from CMV infection beyond one year posttransplant in CMV negative kidney recipients who received a CMV positive kidney (D+/R-). (A) Compare patients with negative or positive CMV-IGRA status at one year after transplantation whereas (B) compare patients with negative or positive CMV IgG status one year after transplantation. CMV DNAemia was taken on clinical decisions. The curves are significantly different in (A) (p=0.01) but not in (B) (p=0.1).
Figure 7
Figure 7
Kaplan-Meier analysis of freedom from CMV infection after one year posttransplant, comparing patients with positive and negative CMV-IGRA status one year after transplantation in CMV negative kidney recipients that received a CMV positive kidney (D+/R-) with a detected CMV infection during the first year post-transplantation (either positive CMV DNAemia and/or positive CMV IgG). Patients were subjected to CMV DNAemia on clinical indication.
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References

    1. Fishman JA. Infection in solid-organ transplant recipients. New Engl J Med. (2007) 357:2601–14. doi: 10.1056/NEJMra064928 - DOI - PubMed
    1. Fowler K, Mucha J, Neumann M, Lewandowski W, Kaczanowska M, Grys M, et al. . A systematic literature review of the global seroprevalence of cytomegalovirus: possible implications for treatment, screening, and vaccine development. BMC Public Health. (2022) 22:1659. doi: 10.1186/s12889-022-13971-7 - DOI - PMC - PubMed
    1. Crough T, Khanna R. Immunobiology of human cytomegalovirus: from bench to bedside. Clin Microbiol Rev. (2009) 22:76–98. doi: 10.1128/CMR.00034-08 - DOI - PMC - PubMed
    1. Smedbråten YV, Sagedal S, Leivestad T, Mjøen G, Osnes K, Rollag H, et al. . The impact of early cytomegalovirus infection after kidney transplantation on long-term graft and patient survival. Clin transplantation. (2014) 28:120–6. doi: 10.1111/ctr.12288 - DOI - PubMed
    1. Sagedal S, Hartmann A, Nordal KP, Osnes K, Leivestad T, Foss A, et al. . Impact of early cytomegalovirus infection and disease on long-term recipient and kidney graft survival. Kidney Int. (2004) 66:329–37. doi: 10.1111/j.1523-1755.2004.00735.x - DOI - PubMed