Characterization of Cytomegalovirus Disease in Solid Organ Transplant Recipients by Markers of Inflammation in Plasma

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.

Increased expression of the homeostatic chemokines CCL19 and CCL21 in clinical and experimental Rickettsia conoriiinfection

“…High levels have also been associated with mycobacterial infections [17,19]. In the present study, we, to the best of our knowledge, for the first time show that rickettsial infection is characterized by increased levels of CCL19 and CCL21 as well as their common receptor CCR7 being prototypical homeostatic chemokines/chemokine receptor.…”

Increased Osteoprotegerin Predicts Poor Virological Outcome During Anticytomegalovirus Therapy in Solid Organ Transplant Recipients

“…We have previously reported plasma levels of various inflammatory markers in this population, 5,17 and OPG levels at baseline seemed strongly associated with general downstream markers of inflammation and immune activation (all variables log transformed): C-reactive protein (r=0.46; P<0.001) and PTX-3 (r=0.23; P<0.001) and endothelial cell activation; vWF (r=0.31; P<0.001) (Fig. 3).…”

“…Although no significant differences in plasma OPG levels were observed comparing patients with similar symptoms with and without confirmed baseline CMV DNAemia, elevated levels were observed with increasing viral load at baseline, in individuals with tissue invasive CMV disease, and in those who failed to eradicate virus at day 49. 5 The arterial wall including vascular endothelial cells and VSMC are major sources of circulating OPG, 12,14,20,21 and the correlation between plasma OPG and vWF and PTX-3, a long pentraxin released from vascular endothelial cells on stimulation with inflammatory cytokines or microorganisms, 22 both at baseline and during antiviral therapy, suggest that plasma OPG levels could reflect vascular inflammation in SOTr patients during CMV infection. 18,19 von Willebrand factor is considered to be one of the best available markers for endothelial cell activation, and in vitro studies have demonstrated increased vWF release from these cells on CMV infection.…”

“…1,2 Cytomegalovirus infection involves interaction between endothelial cells and leukocyte subsets promoting inflammatory responses and endothelial cell activation. 5 Osteoprotegerin (OPG) is a soluble glycoprotein and member of the tumor necrosis factor (TNF) receptor superfamily 6 that lacks transmembrane or cytoplasmic domains and is secreted into the circulation as a soluble biologically active receptor. 4 Thus, we have recently reported that elevated levels of inflammatory markers (e.g., chemokine (C-X-C motif) ligand 16 [CXCL16] and pentraxin-3 [PTX-3]) and markers of endothelial cell activation (e.g., von Willebrand factor [vWF]) are associated with impaired virological and clinical response during anti-CMV therapy in SOTr.…”

Approaches for monitoring of non virus-specific and virus-specific T-cell response in solid organ transplantation and their clinical applications

“…However, CXCL10 (using ELISA) in BAL samples from LTR did not exhibit a significant association with OI post-transplantation [11]. By evaluating plasma markers of inflammation at a baseline time point by ELISA, Rollag et al [12] found that SOT recipients with detectable HCMV DNA in the follow-up had significantly higher levels of CXCL10 than patients with undetectable HCMV DNA. In another study, high levels of CXCL16 (using ELISA) was found in BAL samples from LTR with HCMV disease compared with those detected in patients with asymptomatic HCMV replication [13].…”