Virologic and Immunologic Monitoring of Cytomegalovirus to Guide Preemptive Therapy in Solid-Organ Transplantation

Gerna, Giuseppe; Lilleri, Daniele; Chiesa, A.; Zelini, Paola; Furione, Milena; Comolli, Giuditta; Pellegrini, Carlo; Sarchi, Eleonora; Migotto, C.; Bonora, M. Regazzi; Meloni, Federica; Arbustini, Eloisa

doi:10.1111/j.1600-6143.2011.03636.x

Cited by 87 publications

(88 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…DNAemia was quantified weekly or bi-weekly upon occurrence of active HCMV infection. Pre-emptive antiviral therapy was given to Tx patients reaching a DNAemia cut-off of 300 000 DNA copies ml À1 whole blood (Lilleri et al, 2004;Gerna et al, 2007Gerna et al, , 2011 and consisted of iv ganciclovir (GCV) at a dosage of 5 mg kg À1 twice a day, or oral valganciclovir (VGCV), 900 mg twice a day. Antiviral therapy was continued until the virus disappeared from blood.…”

Section: Methodsmentioning

confidence: 99%

Follicular helper T-cells and virus-specific antibody response in primary and reactivated human cytomegalovirus infections of the immunocompetent and immunocompromised transplant patients

Bruno

Fornara

Zelini

et al. 2016

Journal of General Virology

View full text Add to dashboard Cite

Analysis of human cytomegalovirus (HCMV) primary infection in immunocompetent (n=40) and immunocompromised transplant patients (n=20) revealed that the median peak antibody titre neutralizing infection of epithelial cells was 16-fold higher in immunocompromised patients. The mechanism of this finding was investigated by measuring: (i) HCMV DNAemia; (ii) HCMV neutralizing antibodies; (iii) ELISA IgG antibody titre to HCMV glycoprotein complexes gHgLpUL128L, gHgLgO and gB; and (iv) HCMV-specific (IFN-g + ) CD4 + and CD8 + T-cells. Circulating CXCR5 + CD4 + (memory T follicular helper -T FH -cells) were identified as activated T FH (ICOS + PD-1 ++ CCR7 lo ) and quiescent cells. In the early stages of primary infection, activated T FH cells increased in number. Concomitantly, both neutralizing and IgG antibodies to HCMV glycoproteins reached a peak, followed by a plateau. A stop in antibody rise occurred upon appearance of HCMV-specific CD4 + T-cells, HCMV clearance and progressive reduction in activated T FH cells. The main differences between healthy and transplant patients were that the latter had a delayed DNA peak, a much higher DNA load and delayed activated T FH cells and antibody peaks. Similar events were observed in clinically severe HCMV reactivations of transplant patients. A preliminary analysis of the specificity of the activated T FH cell response to viral proteins showed a major response to the pentamer gHgLpUL128L and gB. In conclusion, in the absence of T-cell immunity, one of the first lines of defence, during primary infection, is conferred by antibodies produced through the interaction of T FH cells and B-cells of germinal centres, resulting in differentiation of B-cells into antibody producing plasma cells.

show abstract

Section: Methodsmentioning

confidence: 99%

Follicular helper T-cells and virus-specific antibody response in primary and reactivated human cytomegalovirus infections of the immunocompetent and immunocompromised transplant patients

Bruno

Fornara

Zelini

et al. 2016

Journal of General Virology

View full text Add to dashboard Cite

show abstract

“…Under proinflammatory conditions, the placenta may express atypical receptors and molecules, facilitating CMV transplacental passage (31)(32)(33)(34). The third hypothesis is that the strong T-cell response observed for cCMV may be directly related to a preceding protracted or high-level viremia: evidence from the transplant field suggests that high viral loads in blood promote higher-level T-cell responses (35). The latter hypothesis would be technically difficult to assess for pregnancy since T-cell assays are performed after the occurrence of CMV infection.…”

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot Assay but Not CMV QuantiFERON Assay Is a Novel Biomarker To Determine Risk of Congenital CMV Infection in Pregnant Women

et al. 2016

View full text Add to dashboard Cite

Cytomegalovirus (CMV) enzyme-linked immunosorbent spot (ELISPOT) and CMV QuantiFERON assays were examined as potential biomarkers predictive of congenital CMV (cCMV) transmission. Fifty-seven pregnant women with primary CMV infection and 23 with nonprimary CMV infection were recruited in the study. Maternal age, CMV IgG avidity, viremia, and viruria were also included among the potential predictors. Spearman's statistical correlation analysis revealed a positive correlation between the CMV ELISPOT and CMV QuantiFERON assay results (P < 0.001), but only the CMV ELISPOT assay correlated with cCMV (P < 0.001). cCMV was positively correlated with maternal viremia and viruria (P < 0.05) and negatively correlated with CMV IgG avidity (P < 0.01). Maternal age and CMV QuantiFERON assay results were not statistically associated with cCMV. CMV-specific cell-mediated immunity detected by the CMV ELISPOT assay plays a critical role in cCMV. Congenital cytomegalovirus (cCMV) infection affects about 0.7% of newborns worldwide (1-3). The clinical CMV-related sequelae at birth are highly variable and related to maternal serostatus and the time of onset of congenital infection during pregnancy (4-9). Whenever clinically evident, CMV-induced damages include sensorineural hearing loss (SNHL), visual impairment, delayed psychomotorial development, and retardation (10-13). Understanding the risk factors and biomarkers associated with the maternal transmission of CMV infection represents a leading priority for both diagnosis and clinical management of cCMV. Recently, it was shown that maternal CMV cell-mediated immunity (CMI) plays a critical role in determining cCMV (14-16). Several assays are available to assess CMV-specific CMI, and the large majority of these assays are based on interferon gamma (IFN-␥) release assays (IGRAs) (17)(18)(19)(20). In this study, two IGRAs that detect CMV-specific CMI, the CMV enzyme-linked immunosorbent spot (ELISPOT) and CMV QuantiFERON assays, were compared for their prediction of cCMV. Both the CMV ELISPOT and CMV-QuantiFERON assays detect IFN-␥ produced by antigen-stimulated peripheral blood mononuclear cells (PBMCs). The main differences between the assays include the antigen stimulus composition, with stimulation of CD8 ϩ T-cell responses in the CMV QuantiFERON assay (21) and stimulation of both CD4 ϩ and CD8 ϩ T-cell responses in the CMV ELISPOT assay (22, 23). Moreover, the CMV QuantiFERON assay detects IFN-␥ in a volume of ϳ1 ml of whole blood, while the CMV ELISPOT assay detects IFN-␥ secreted by ϳ2 ϫ 10 5 PBMCs (22, 23). Recent studies suggest that the CMV ELISPOT and CMV QuantiFERON assays may display large variability on an individual basis (24,25).In order to have a more comprehensive view of the maternal factors associated with cCMV, this study also investigated maternal parameters such as maternal age, viremia, viruria, and CMV immunoglobulin G (IgG) avidity.(The data in this study were partly presented at the Congenital CMV Conference, Brisbane, Australia, 2015.) MATERIALS AND METHOD...

show abstract

“…However, other transplantation studies have also indicated an important role for CD4 1 T cells in CMV viral control after transplantation (24)(25)(26)(27)(28). Interestingly, in a study of renal, heart, and lung transplantation recipients, lung transplantation recipients had Figure 4.…”

Section: Discussionmentioning

confidence: 99%

Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation

Snyder¹,

Chan²,

Kwon³

et al. 2016

Am J Respir Crit Care Med

View full text Add to dashboard Cite

Rationale: Cytomegalovirus (CMV), which is one of the most common infections after lung transplantation, is associated with chronic lung allograft dysfunction and worse post-transplantation survival. Current approaches for at-risk patients include a fixed duration of antiviral prophylaxis despite the associated cost and side effects.Objectives: We sought to identify a specific immunologic signature that predicted protection from subsequent CMV.Methods: CMV-seropositive lung transplantation recipients were included in the discovery (n = 43) and validation (n = 28) cohorts. Polyfunctional CMV-specific immunity was assessed by stimulating peripheral blood mononuclear cells with CMV pp65 or IE-1 peptide pools and then by measuring T-cell expression of CD107a, IFN-g, tumor necrosis factor-a (TNF-a), and IL-2. Recipients were prospectively monitored for subsequent viremia. A Cox proportional hazards regression model that considered cytokine responses individually and in combination was used to create a predictive model for protection from CMV reactivation. This model was then applied to the validation cohort.Measurements and Main Results: Using the discovery cohort, we identified a specific combination of polyfunctional T-cell subsets to pp65 that predicted protection from subsequent CMV viremia (concordance index 0.88 [SE, 0.087]

show abstract

Virologic and Immunologic Monitoring of Cytomegalovirus to Guide Preemptive Therapy in Solid-Organ Transplantation

Cited by 87 publications

References 37 publications

Follicular helper T-cells and virus-specific antibody response in primary and reactivated human cytomegalovirus infections of the immunocompetent and immunocompromised transplant patients

Follicular helper T-cells and virus-specific antibody response in primary and reactivated human cytomegalovirus infections of the immunocompetent and immunocompromised transplant patients

Cytomegalovirus (CMV) Enzyme-Linked Immunosorbent Spot Assay but Not CMV QuantiFERON Assay Is a Novel Biomarker To Determine Risk of Congenital CMV Infection in Pregnant Women

Polyfunctional T-Cell Signatures to Predict Protection from Cytomegalovirus after Lung Transplantation

Contact Info

Product

Resources

About