Meet in the middle: Could cell mediated-immunity assays be the answer for ideal Cytomegalovirus prophylaxis after lung transplantation? Observational study from a single center with intermittent antiviral prophylaxis.

BACKGROUND: Cytomegalovirus (CMV) can cause tissue-invasive disease and indirect effects after lung transplantation (LTx) such as acute rejection episodes and chronic lung allograft dysfunction. Monitoring CMV-specific cell immune recovery (CMV-CIR) after LTx can individualize CMV risks and establish better antiviral approach. This study evaluated the dynamics of CMV-CIR, using QuantiFERON-CMV assay (Qiagen Group), in the first year after LTx. METHODS: Prospective observational cohort study included lung transplant recipients from December/2015 to December/2016. Universal antiviral prophylaxis with intravenous ganciclovir 5 mg/kg/day 3 days/week for 3 months was given for CMV-seropositive recipients (R+) and only CMV-seropositive donor and negative recipient (D+/R-) received a 6-month-prophylaxis with ganciclovir and valganciclovir, on alternate days, in the first 3 months and then, 3 more months of valganciclovir. QuantiFERON-CMV was measured at the same time points of surveillance bronchoscopies. CMV infection was defined as any DNAemia detected and CMV disease with proven biopsy or antigenemia pp65 above 10 cells/300.000 neutrophils. RESULTS: Thirty-eight patients were included. On days 45, 90, and 365 days post-LTx, 60%, 72%, and 81% QuantiFERON-CMV were reactive, respectively. Eleven patients (28.9%) presented CMV-disease and 27 DNAemia/CMV infections. Reactive tests were able to predict CMV disease only at 90 days after LTx (p = .027) but failed on DNAemia/CMV infection (p = .148). Daily prophylaxis, for D+/R- patients (13.2%), remained as an independently associated factor for not achieving reactive QuantiFERON-CMV (adjusted OR .27, 95%CI .12-.60, p = .02). CONCLUSION: QuantiFERON-CMV may be another diagnostic tool to help stratify CMV-disease risk and individualized antiviral prophylaxis after LTx.

Epstein-Barr virus oral shedding and viremia and their association with oral hairy leukoplakia in HIV+ individuals.

OBJECTIVE: To assess the oral shedding and viremia of Epstein-Barr virus (EBV) in HIV-positive patients and their relationship with oral hairy leukoplakia (OHL). METHODOLOGY: A total of 94 HIV-positive patients were included in the study, in which blood and saliva samples were collected for EBV quantification. Data on gender, age, time of HIV seropositivity, combined antiretroviral therapy (cART), CD4+ T-cell counts, and HIV viral load were collected. OHL diagnosis was based on histopathological examination and EBV in situ hybridization. RESULTS: The EBV load in the 94 HIV-positive patients was higher in saliva than in blood (2.4 and 1.6, respectively), and there was a positive correlation between EBV oral shedding and viremia (p = 0.001). Twenty (21.27%) patients had OHL and also a higher EBV load in saliva (mean log10  = 3.11) compared to those who had no OHL (p = 0.045). Presence of OHL was only associated with age (p = 0.030). CONCLUSION: In HIV-positive patients, the presence of OHL was associated with EBV oral shedding but not with viremia, regardless of the amount of circulating CD4+ T cells.

Assessment of bone metabolism biomarkers in serum and saliva of cirrhotic patients.

OBJECTIVE: To assess the serum and salivary levels of biomarkers related to bone metabolism in cirrhotic patients as well as the evidence of osteoporotic changes on panoramic radiographs. MATERIALS AND METHODS: Thirty-eight cirrhotic patients underwent anamnesis and physical examination. Specimens of blood and saliva were collected for evaluation by using Luminex™ xMAP technology to quantify RANKL, OPG, IL-1ß, IL-6 and TNF-α. Panoramic radiographs were evaluated based on the mandibular cortical index (MCI) and the resulting data were compared to the expression of biomarkers in serum and saliva. Descriptive data analysis was performed and the Mann-Whitney's test and Spearman's correlation were used. RESULTS: Most of the sample consisted of males (68.4%) who had cirrhosis mostly resulting from alcoholism (28.9%). Median concentration values of RANKL (74.44 pg/mL), IL-1 ß (45.91 pg/mL), IL-6 (67.69 pg/mL) and TNF-α (5.97 pg/mL) in saliva were higher than those observed in serum. In 72.7% of the panoramic radiographs, MCI was found to be suggestive of osteoporotic changes. No statistically significant correlation was observed between salivary and serum expressions of biomarkers or between biomarkers and MCI. CONCLUSION: RANKL, OPG, IL-1ß, IL-6 and TNF-α are expressed differently in serum and saliva and the concentration of these biomarkers is not related to MCI. CLINICAL RELEVANCE: This study contributes to the study of the mechanisms of osteoporosis in cirrhotic individuals.

Quantification of Torque Teno Virus (TTV) in plasma and saliva of individuals with liver cirrhosis: a cross sectional study.

Introduction: Torque teno virus (TTV) has been pointed as an endogenous marker of immune function, the objective of this study was to investigate the TTV viral load in plasma and saliva of cirrhotic individuals and correlate it with clinical characteristics. Methods: Blood, saliva, clinical data from records and laboratory tests were collected from 72 cirrhotic patients. Plasma and saliva were submitted to real-time polymerase chain reaction for quantification of TTV viral load. Results: The majority of the patients presented decompensated cirrhosis (59.7%) and 47.2% had alterations in the white blood series. TTV was identified in 28 specimens of plasma (38.8%) and in 67 specimens of saliva (93.0%), with median values of TTV copies/mL of 90.6 in plasma and 245.14 in saliva. All the patients who were positive for TTV in plasma were also positive in saliva, with both fluids having a moderately positive correlation for the presence of TTV. There was no correlation between TTV viral load, either in plasma or in saliva, and any of the variables studied. Conclusion: TTV is more frequently found and in greater amount in the saliva than in the plasma of cirrhotic patients. There was no correlation between TTV viral load and clinical parameters.

Detection of polyomavirus microRNA-5p expression in saliva shortly after kidney transplantation.

Background: MicroRNAs (miRNAs) of polyomavirus (PyV) are present in several biological fluids and are suggested to be relevant viral factors for monitoring its persistence. Aim: To evaluate the effect of an immunosuppressive regimen on the status of PyV-miRNA-5p in the oral cavity. Materials and Methods: The JCPyV, BKPyV, MCPyV miRNA-5p were investigated in paired saliva and plasma samples obtained from 23 patients before and shortly after renal-transplantation by using real-time RT-PCR. Results: Overall, within a short-time after transplantation, patients exhibited decreased numbers of leukocyte and lymphocyte as well as low levels of creatinine. During the clinical management of the patients, a significant amount of saliva samples were positive for JCPyV and BKPyV miRNA-5p (range: 26%-91%) compared to paired plasma samples (range: 9%-35%). Among the two polyomaviruses showing positive expression of miRNA-5p, BKPyV presented the highest positivity in saliva (91%) and MCPyV-miRNA-5p was constantly negative in both saliva and plasma samples. Compared to the time before transplantation, a significant reduction in the expression of JCPyV-miRNA-5p was observed in saliva samples obtained after transplantation. Conclusions: Altogether, these data suggest that additional investigations of polyomavirus miRNA-5p in saliva should be performed shortly after renal-transplantation to evaluate the potential role in early viral reactivation.