Abstract
BackgroundWhile 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 MethodsSolid 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.ResultsThe 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.ConclusionOur 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.
Highlights
Cytomegalovirus (CMV) is a major viral pathogen affecting solid organ transplant recipients, and is responsible for substantial morbidity in affected individuals
When performing Receiver Operating Characteristic (ROC) analyses, vWF, CRP, IP-10, CCL21 and sTNF-R1 were found to be associated with detectable CMV DNA in plasma as opposed to patients with similar symptoms and CMV DNAemia below level of quantification (LLoQ)
Once included together with potential confounders in the multivariable logistic regression IP-10 (OR [per each 10 units increase]: 1.498; 95% CI: 1.221–1.839; P,0.001), CRP (OR: 1.002; 95%CI: 1.000–1.004; P = 0.046), and time from transplant (OR: 0.449; 95% CI: 0.290–0.696; P = 0.001) were confirmed to be independently associated with positive CMV DNAemia
Summary
Cytomegalovirus (CMV) is a major viral pathogen affecting solid organ transplant recipients, and is responsible for substantial morbidity in affected individuals. The clinical manifestations of CMV include an acute viral syndrome as well as tissue invasive diseases including pneumonitis, hepatitis and gastrointestinal disease [1]. In addition to these CMV-induced manifestations, CMV has immunomodulatory effects that predispose to opportunistic infections as well as acute and chronic allograft rejection in the infected host [1,2]. 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
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