1,721,038 research outputs found
Neutralizing and ELISA IgG antibodies to human cytomegalovirus glycoprotein complexes may help date the onset of primary infection in pregnancy
No full textHuman cytomegalovirus end-organ disease is associated with high or low systemic viral load in preemptively treated solid-organ transplant recipients.
No full textHuman cytomegalovirus (HCMV) end-organ disease in solid-organ transplant recipients (SOTR) may be associated with either high or low HCMV load in blood. In transplantation Centers where the preemptive therapy approach is adopted, antiviral therapy of systemic HCMV infections is initiated upon reaching pre-determined cut-off levels of viral DNA in blood, whereas no guidelines are provided for local end-organ infection/disease. In the latter case, clinicians often start antiviral treatment without defining the etiology of local symptoms. Here, we describe 14 cases of SOTR, in which a documented HCMV end-organ disease was observed. Nine patients had a systemic viral load lower than the cut-off for preemptive therapy and were treated based on viral load of local HCMV disease. The remaining five patients had a systemic viral load greater than the preemptive therapy cut-off and were efficiently treated for both the systemic and the local HCMV disease. Thus, HCMV infection in the post-transplant period must be monitored virologically both in blood and locally. End-organ disease in preemptively treated patients, seems to be associated with lack of development (primary HCMV infection) or reconstitution (reactivated infection) of HCMV-specific CD4+ and CD8+ T-cell immunity or with its functional impairment
Pre-transplant IE1-specific T-cell response and CD8+ T-cell count as predictive markers of treated HCMV reactivation in kidney transplant recipients
No full textBackground: Human cytomegalovirus (HCMV) infection represents a significant
complication for kidney transplant recipients (KTRs). The goal of this study was to
evaluate potential immunological markers at pre-transplant in HCMVseropositive
KTRs for predicting HCMV severe reactivation (e.g treated HCMV
reactivation) during the first year after transplant.
Methods: Before transplant, lymphocyte count was measured in whole blood
and HCMV-specific T-cell response was determined using ELISpot assay after
stimulation with pp65, IE-1 and IE-2 peptides pool. HCMV DNA was monitored
during the first year after transplant. Among the 65 KTRs enrolled, 44 (68%)
patients had HCMV self-resolving reactivation (Controllers) while 21 (32%)
required antiviral treatment for HCMV reactivation (Non-Controllers).
Results: No significant difference in CD4 T-cell count was observed, but
Controllers had higher CD8+ T-cell counts compared to Non-Controllers.
Based on ROC analysis, a CD8+ T-cell count ≥215 cells/ml was associated with
a lower incidence of HCMV reactivation after transplant. Additionally, a higher IE-
1-specific T-cell response was observed in Controllers and patients with IE1-
specific T-cell response ≥60 spots showed a reduced incidence of HCMV
reactivation and lower DNAemia peak.
Discussion: Lymphocyte counts and HCMV-specific T-cell response can be
measured at pre-transplant in KTRs in order to efficiently predict the risk of
treated HCMV reactivation during the first year after transplant. Potential cut-off
and diagnostics algorithm should be better investigated in a large patients setting
Systemic and local human cytomegalovirus-specific T-cell response in lung transplant recipients
No full textIt is debated whether human cytomegalovirus (HCMV) infection/disease of the pulmonary compartment in lung transplant recipients (LTRs) may be controlled by the HCMV-specific systemic T-cell response or requires a local (lung) T-cell response. Systemic and local HCMV loads were investigated in parallel by real-time PCR in 20 LTRs. T-cell responses were measured by intracellular cytokine staining of HCMV-specific IFN-? + CD4+ and CD8+ T-cells in PBMC, and by enzyme-linked immunospot (ELISpot) assay in lung (BAL) mononuclear cells. Patients were grouped at time of peak of infection based on viral load in blood and BAL. Immunological testing results showed that five patients with no HCMV infection (either local or systemic) had both local and systemic T-cell responses; four patients with systemic infection had no systemic T-cell response; five patients with both systemic and lung infection had neither local nor systemic T-cell responses; and six patients with lung infection had no local and a partial (only CD8+ in the absence of CD4+) systemic T-cell response. These results indicate that local immunity is associated with resolution of lung infection. Systemic T-cell response alone is not sufficient to provide lung protection from HCMV infection
Systemic and local human cytomegalovirus-specific T-cell response in lung transplant recipients
No full textIt is debated whether human cytomegalovirus (HCMV) infection/disease of the pulmonary compartment in lung transplant recipients (LTRs) may be controlled by the HCMV-specific systemic T-cell response or requires a local (lung) T-cell response. Systemic and local HCMV loads were investigated in parallel by real-time PCR in 20 LTRs. T-cell responses were measured by intracellular cytokine staining of HCMV-specific IFN-? + CD4+ and CD8+ T-cells in PBMC, and by enzyme-linked immunospot (ELISpot) assay in lung (BAL) mononuclear cells. Patients were grouped at time of peak of infection based on viral load in blood and BAL. Immunological testing results showed that five patients with no HCMV infection (either local or systemic) had both local and systemic T-cell responses; four patients with systemic infection had no systemic T-cell response; five patients with both systemic and lung infection had neither local nor systemic T-cell responses; and six patients with lung infection had no local and a partial (only CD8+ in the absence of CD4+) systemic T-cell response. These results indicate that local immunity is associated with resolution of lung infection. Systemic T-cell response alone is not sufficient to provide lung protection from HCMV infection
Human cytomegalovirus end-organ disease is associated with high or low systemic viral load in preemptively treated solid-organ transplant recipients
No full textHuman cytomegalovirus (HCMV) end-organ disease in solid-organ transplant recipients (SOTR) may be associated with either high or low HCMV load in blood. In transplantation Centers where the preemptive therapy approach is adopted, antiviral therapy of systemic HCMV infections is initiated upon reaching pre-determined cut-off levels of viral DNA in blood, whereas no guidelines are provided for local end-organ infection/disease. In the latter case, clinicians often start antiviral treatment without defining the etiology of local symptoms. Here, we describe 14 cases of SOTR, in which a documented HCMV end-organ disease was observed. Nine patients had a systemic viral load lower than the cut-off for preemptive therapy and were treated based on viral load of local HCMV disease. The remaining five patients had a systemic viral load greater than the preemptive therapy cut-off and were efficiently treated for both the systemic and the local HCMV disease. Thus, HCMV infection in the post-transplant period must be monitored virologically both in blood and locally. End-organ disease in preemptively treated patients, seems to be associated with lack of development (primary HCMV infection) or reconstitution (reactivated infection) of HCMV-specific CD4+ and CD8+ T-cell immunity or with its functional impairment
In Vitro Model for the Study of the Dissociation of Increasing Antigenemia and Decreasing DNAemia and Viremia during Treatment of Human Cytomegalovirus Infection with Ganciclovir in Transplant Recipients
No full textThe paradox phenomenon (i.e., the dissociation of increasing antigenemia and decreasing DNAemia and viremia) that occurs during treatment of human cytomegalovirus (HCMV) infections with ganciclovir (Gcv), in transplant recipients, was investigated by use of an in vitro model for the study of interactions between polymorphonuclear leukocytes and endothelial cells. The paradox phenomenon was reproduced in vitro in the presence of Gcv and, to a much lesser extent, in the presence of cidofovir, but not in the presence of foscarnet. The pathogenetic basis for such a paradox response was found, by use of drug concentrations in the range of 90%-99% of the inhibitory dose, to rely on the partial synthesis of HCMV phosphoprotein 65. The opposite situation (i.e., the simultaneous increase of antigenemia, viremia, and DNAemia), which is observed in clinical conditions associated with inefficacy of treatment due to drug-resistant strains, was also reproduced in vitro by use of drug-resistant HCMV strains. The conclusion for clinicians is that antiviral therapy must be changed only in the latter case
Comparison of the T-cell response to human cytomegalovirus (HCMV) as detected by cytokine flow cytometry and QuantiFERON-CMV assay in HCMV-seropositive kidney transplant recipients
No full text: Human cytomegalovirus (HCMV)-specific T-cell response in kidney transplant recipients (KTR) helps to identify patients at risk for severe infection. To assess the T-cell response, this study compared our in-house developed reference test, based on T-cell (both CD4+ and CD8+) stimulation by autologous HCMV-infected dendritic cells (iDC) and subsequent detection by cytokine flow cytometry (CFC-iDC), with the Quanti-FERON-CMV (QF-CMV) assay. Fifty-three HCMV-seropositive KTR were enrolled. At the DNAemia peak, 33 (62%) had low viral load (LVL, 3x105 DNA copies/mL) infection treated with antivirals, and one LVL patient (2%) tissue-invasive disease alone. Both assays showed a delayed recovery of HCMV-specific T-cell immunity in HVL vs LVL patients. Immune reconstitution kinetics did not significantly differ between the two assays in HVL patients. QF-CMV and CFC-iDC showed comparable sensitivities, but QF-CMV had a lower (although not significantly) specificity. Indeed, 7/19 HVL patients (37%) were erroneously considered protected from severe infection by QF-CMV, whereas CFC-iDC misidentified only 3/19 (16%) patients as protected. Although our reference test takes longer to complete, it appears slightly better at predicting patients at risk for severe HCMV infection. Moreover, QF-CMV may provide false negative results with some HLA types
Waves of SARS-CoV-2 infections in a group of vaccinated psoriatic patients treated with biological drugs: experience from a tertiary hospital located in Northern Italy
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