Evaluation of serum Epstein-Barr virus envelope glycoproteins antibodies and their association with systemic autoimmune diseases.

Systemic autoimmune diseases (SADs) are a growing spectrum of autoimmune disorders that commonly affect multiple organs. The role of Epstein-Barr virus (EBV) infection or reactivation as a trigger for the initiation and progression of SADs has been established, while the relationship between EBV envelope glycoproteins and SADs remains unclear. Here, we assessed the levels of IgG, IgA, and IgM against EBV glycoproteins (including gp350, gp42, gHgL, and gB) in serum samples obtained from patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and found that RA and SLE patients exhibited a statistically significant increase in the levels of 8 and 11 glycoprotein antibodies, respectively, compared to healthy controls (p < 0.05). The LASSO model identified four factors as significant diagnostic markers for RA: gp350 IgG, gp350 IgA, gHgL IgM, and gp42 IgA; whereas for SLE it included gp350 IgG, gp350 IgA, gHgL IgA, and gp42 IgM. Combining these selected biomarkers yielded an area under the curve (AUC) of 0.749 for RA and 0.843 for SLE. We subsequently quantified the levels of autoantibodies associated with SADs in mouse sera following immunization with gp350. Remarkably, none of the tested autoantibody levels exhibited statistically significant alterations. Elevation of glycoprotein antibody concentration suggests that Epstein-Barr virus reactivation and replication occurred in SADs patients, potentially serving as a promising biomarker for diagnosing SADs. Moreover, the absence of cross-reactivity between gp350 antibodies and SADs-associated autoantigens indicates the safety profile of a vaccine based on gp350 antigen.

Radiofrequency Ablation Following Downstaging of Hepatocellular Carcinoma by Using Transarterial Chemoembolization: Long-term Outcomes.

Background Transarterial chemoembolization (TACE) is an effective downstaging procedure for hepatocellular carcinoma (HCC). However, knowledge of the effectiveness of radiofrequency ablation (RFA) after downstaging of HCC is currently lacking. Purpose To evaluate the clinical outcomes of RFA after downstaging of HCC by using TACE. Materials and Methods This retrospective study investigated a cohort of patients who underwent RFA with curative intent after downstaging with TACE to meet Milan criteria (one lesion up to 5 cm or no more than three lesions ≤3 cm without vascular invasion or extrahepatic metastasis) from January 2012 to July 2017. A control group of patients initially meeting the Milan criteria also underwent RFA as first-line treatment in the same period. Overall survival (OS), disease-free survival (DFS), and major complication rates were compared by using the log-rank test. To reduce potential bias, a propensity score analysis was also performed. Results There were 72 patients (median age, 56.5 years; range, 30-78 years; 67 men) in the downstaging group and 357 patients meeting the Milan criteria (median age, 58.0 years; range, 25-87 years; 313 men) included in this study. After propensity score matching, the 1-, 3-, and 5-year OS rates were 99%, 80%, and 66%, respectively, for the patients in the downstaging group and 94%, 84%, and 69%, respectively, for the patients in the Milan criteria group. The 1-, 3-, and 5-year DFS rate were 73%, 34%, and 24% for the downstaging group and 74%, 43%, and 37% for the Milan criteria group. There were no differences in the OS, DFS, or major complication rates between the two groups (P = .74, P = .39, P = .73, respectively). Conclusion The long-term patient survival and major complication rates of radiofrequency ablation following transarterial chemoembolization downstaging for hepatocellular carcinoma were similar to that of patients initially meeting the Milan criteria. © RSNA, 2019 See also the editorial by vanSonnenberg and Mueller in this issue.

Development and Validation of Tumor-educated Blood Platelets Integrin Alpha 2b (ITGA2B) RNA for Diagnosis and Prognosis of Non-small-cell Lung Cancer through RNA-seq.

Background: Currently, there are no molecular biomarkers for the early detection of non-small-cell lung cancer (NSCLC). This study focused on identifying RNAs found on tumor-educated blood platelets (TEPs) for detecting stage I NSCLC. Methods: Platelet RNAs, isolated from the blood of 9 patients with NSCLC (stages I and II) and 8 healthy controls, were analyzed using RNA-seq. ITGA2B was selected as a candidate marker. Two different Polymerase Chain Reactions (PCR) were used to measure ITGA2B in platelet samples from healthy controls (n = 150), patients with NSCLC (n = 243), and patients with benign pulmonary nodules (n = 141) in two cohorts. Results: Platelet ITGA2B levels were significantly higher (p < 0.001) in patients with NSCLC than in all controls. The diagnostic accuracy of ITGA2B was area under the curve (AUC) of 0.922 [95% confidence interval (CI), 0.892-0.952], sensitivity of 92.8%, and specificity of 78.6% in the test cohort and 0.888, 91.2%, and 56.5% in the validation cohort for NSCLC by quantitative real time PCR (q-PCR). Furthermore, ITGA2B maintained diagnostic accuracy for patients with NSCLC using Droplet Digital PCR (ddPCR) and the other type of internal control, Ribosomal Protein L32 (RPL32) [ddPCR: 0.967 (0.929-1.000) and RPL32: 0.847(0.773-0.920)]. A nomogram incorporating ITGA2B, carcinoembryonic antigen (CEA) and stage could predict the overall survival (C-index = 0.756). Conclusions: TEP ITGA2B is a promising marker to improve identification of patients with stage I NSCLC and differentiate malignant from benign lung nodules.

Association between GNB3 c.825C > T polymorphism and the risk of overweight and obesity: A meta-analysis.

BACKGROUND: The association between G protein ß-polypeptide 3 gene (GNB3) c.825C > T polymorphism (rs5443) and the risk of overweight/obesity has been investigated in many published studies, but the results were conflicting and inconclusive. A meta-analysis was performed to make a more accurate assessment of the relationship. METHODS: The PubMed, ProQuest Health & Medical Complete, Web of Science, Chinese Biomedical Medical databases (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wan Fang databases were searched to identify eligible literatures. Pooled odds ratios (ORs) with the corresponding 95% confidence intervals (CIs) were used to assess the strength of association between GNB3 c.825C > T polymorphism and overweight/obesity. RESULTS: Eleven articles including 15 case-control studies with a total of 10,396 subjects (3171 cases of overweight/obesity and 7225 controls) were enrolled in the meta-analysis. The GNB3 c.825C > T was significantly associated with overweight/obesity under a recessive model (OR = 1.22, 95% CI: 1.04-1.44, P = 0.015). Moreover, the GNB3 825T allele was obviously associated with overweight alone in all inheritable models (P < 0.05) except in a recessive model (P = 0.084). In the stratification analysis by potential confounding variables, a significant association was observed between GNB3 c.825C > T polymorphism and overweight/obesity risk in males under an allelic model (P = 0.008), a homozygous model (P = 0.014), a recessive model (P = 0.005), and a dominant model (P = 0.049). And the results also showed that GNB3 c.825C > T polymorphism was significantly associated with overweight/obesity in subgroups of mean age less than 30 years, consistent with HWE, and high-quality studies (P = 0.027, P = 0.043, P = 0.040, respectively) under a recessive model, but not in other subgroups. Meta-regression also revealed that P value of HWE, publication year, and the quality scores of studies were the sources of heterogeneity in a recessive model and an allelic model. "Leave one out" sensitivity analyses indicated that the association was more significant after excluding some studies. The funnel plot and Egger's linear regression test and Begg's test revealed no apparent publication bias. CONCLUSION: This meta-analysis suggests that the presence of TT homozygote might be one of the genetic factors susceptible to overweight/obesity and that males or aged under 30 years increase the genetic susceptibility.

Influence of G-protein ß-Polypeptide 3 C825T Polymorphism on Antihypertensive Response to Telmisartan and Amlodipine in Chinese Patients.

BACKGROUND: G-protein ß-polypeptide 3 (GNB3) is a ß subunit isoform of G-protein that plays important role in signal transduction of membrane G-protein coupled receptors (GPCRs). The GNB3 splice variant C825T (rs5443) is associated with risk for essential hypertension (EH) and efficacy of therapeutic drugs targeting GPCRs. It is unknown whether the polymorphism is associated with blood pressure (BP) response to telmisartan or amlodipine, two widely prescribed antihypertensive drugs. METHODS: A total of 93 subjects initially diagnosed as EH were recruited and underwent a 4-week treatment with telmisartan (42 patients) or amlodipine (51 patients) monotherapy. Both baseline and after-treatment BP were measured. GNB3 C825T polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Baseline systolic BP (SBP) and diastolic BP (DBP) were comparable among C825T genotypes in both telmisartan and amlodipine treatment groups. Patients with the CT or TT genotypes showed significantly lower body mass index (BMI) as compared with CC homozygotes in both groups (P < 0.05, respectively). GNB3 825TT homozygotes showed significantly higher after-treatment DBP and mean arterial pressure (MAP) than those carrying at least one 825C allele (P < 0.01) in the telmisartan treatment group. No difference in after-treatment SBP, DBP, and MAP levels among C825T genotypes was observed in the amlodipine treatment group. No significant difference in absolute changes in BP levels was observed among the genotypes in either treatment group. CONCLUSION: The GNB3 C825T splice variant is associated with the DBP-lowering effect of telmisartan but not amlodipine in Chinese EH patients.