Characterization of cytomegalovirus disease in solid organ transplant recipients by markers of inflammation in plasma

Halvor Rollag, Thor Ueland, Anders Asberg, Anders Hartmann, Alan G Jardine, Atul Humar, Mark D Pescovitz, Angelo A Bignamini, Pål Aukrust, Halvor Rollag, Thor Ueland, Anders Asberg, Anders Hartmann, Alan G Jardine, Atul Humar, Mark D Pescovitz, Angelo A Bignamini, Pål Aukrust

Abstract

Background: While several studies have examined the general inflammatory responses in relation to cytomegalovirus infection, the identification of the various inflammatory mediators as well as their relative importance is far from clear.

Patients and methods: Solid organ recipients enrolled in an international multicenter trial of cytomegalovirus disease treatment (the VICTOR study) were analyzed (n = 289) (ClinicalTrials.gov NCT00431353). Plasma markers of inflammation and endothelial cell activation were assessed at baseline by enzyme immunoassays.

Results: The major findings were: (i) Plasma levels of the CXC-chemokine interferon-inducible protein-10 (P<0.001) and C-reactive protein (P = 0.046) were independently associated with the presence of cytomegalovirus DNAemia above lower level of quantification. (ii) High levels of CC-chemokine ligand 21 (P = 0.027) and pentraxin 3 (P = 0.033) were independently associated with tissue invasive cytomegalovirus disease as opposed to cytomegalovirus syndrome.

Conclusion: Our findings illustrate the complex interaction between cytomegalovirus and the immune system, involving a wide range of inflammatory mediators that could be associated to disease manifestations in cytomegalovirus related disease.

Conflict of interest statement

Competing Interests: The authors have the following interests. Dr. Åsberg is a former employee of F. Hoffmann-La Roche Ltd. (between 2000 and 2003) and served as a consultant to F. Hoffmann-La Roche Ltd during the study dealing with study specific issues. Drs. Humar, Jardine, Hartmann and Rollag have performed consultancy work for F. Hoffmann - La Roche Ltd. Drs Aukrust and Ueland have no conflicts of interest to report. Dr. Bignamini was employed by Hyperphar during the study, which was a sub-contractor for F.Hoffmann-La Roche Ltd, hired to perform data management and statistical analyses. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Figure 1. Markers of inflammation in relation…
Figure 1. Markers of inflammation in relation to CMV-DNAemia.
Plasma levels of markers of inflammation, marker of endothelial cell activation and chemokines in relation to presence or absence of CMV DNAemia in patients suspected to have CMV disease. The P-values are adjusted for potential confounders (i.e., age, sex and time from transplantation). P-values

Figure 2. Markers of inflammation in relation…

Figure 2. Markers of inflammation in relation to CMV-disease.

Plasma levels of markers of inflammation,…

Figure 2. Markers of inflammation in relation to CMV-disease.
Plasma levels of markers of inflammation, marker of endothelial cell activation and chemokines in relation to clinical manifestation of CMV disease as either CMV syndrome or tissue invasive CMV disease. The P-values are adjusted for potential confounders (i.e., age, sex, viral load and time from transplantation). TI, tissue invasive. P-values
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References
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Figure 2. Markers of inflammation in relation…
Figure 2. Markers of inflammation in relation to CMV-disease.
Plasma levels of markers of inflammation, marker of endothelial cell activation and chemokines in relation to clinical manifestation of CMV disease as either CMV syndrome or tissue invasive CMV disease. The P-values are adjusted for potential confounders (i.e., age, sex, viral load and time from transplantation). TI, tissue invasive. P-values

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