Decreased antigen-specific T-cell proliferation by moDC among hepatitis B vaccine non-responders on haemodialysis.
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ABSTRACT:
SUBMITTER: Verkade MA
PROVIDER: S-EPMC2780615 | biostudies-other | 2007 Jun
REPOSITORIES: biostudies-other
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Project description: Not available
| S-EPMC9383466 | biostudies-literature
Project description:The emergence of a vaccine against hepatitis B has proven to be an important milestone in the prevention of this disease; however, 5%-10% of vaccinated individuals do not generate an immune response to the vaccine, and its molecular mechanism has not been clarified. In this study, single-cell RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from three volunteers with a high immune response (HR) and three with no immune response (NR) to the hepatitis B vaccine. We found that the antigen-presenting activity scores of various antigen-presenting cells, the mitogen-activated protein kinase (MAPK) pathway activity scores of naive B cells, and the cell activity scores of three types of effector T cells were significantly decreased, whereas the cytotoxicity scores of CD3highCD16lowKLRG1high natural killer T (NKT) cells were significantly increased in the NR group compared with those in the HR group. Additionally, the expression levels of some classical molecules associated with distinct signaling pathways-including HLA-B, HLA-DRB5, BLNK, BLK, IL4R, SCIMP, JUN, CEBPB, NDFIP1, and TXNIP-were significantly reduced in corresponding subsets of PBMCs from the NR group relative to those of the HR group. Furthermore, the expression of several cytotoxicity-related effector molecules, such as GNLY, NKG7, GZMB, GZMM, KLRC1, KLRD1, PRF1, CST7, and CTSW, was significantly higher in CD3highCD16lowKLRG1high NKT cells derived from non-responders. Our study provides a molecular basis for the lack of response to the hepatitis B vaccine, including defective antigen presentation, decreased T cell activity, and reduced IL-4 secretion, as well as novel insight into the role of NKT cells in the immune response to the hepatitis B vaccine.
| S-EPMC10431960 | biostudies-literature
Project description:Individuals fail to elicit protective antibody after hepatitis B vaccination remain at risk for hepatitis B virus infection. Analysis of the transcriptome of peripheral blood mononuclear cells (PBMCs) is essential to elucidate the characteristics of gene expression in non-responders. In this study, we enrolled seven responders who had received three injections and seven non-responders who had six injections of hepatitis B vaccine before. All the participants were then vaccinated with a three-dose boost regimen. Microarray analysis and Luminex assay were applied to examine mRNA expression and Th1/Th2/Th9/Th17/Th22/Treg cytokine and chemokine profiles in non-responders and responders. Differentially expressed genes in PBMCs of non-responders at 5 time points, i.e. pre-vaccination, 3rd, 7th, 28th day post the first dose vaccination and 7th day post the second dose vaccination indicated a dense network trend. Compared with responders, nine coding genes (BPI, DEFA1B, DEFA4, CEACAM8, MMP8, FOLR3, LTF, TCN1 and TKTL1) were significantly up-regulated in non-responders at all 5 time points, which could probably be the characteristic genes in hepatitis B vaccine non-responsiveness. Gene ontology analysis revealed that most of the DEGs were related with immune responses. Validation results of these 9 genes using quantitative real-time polymerase chain reaction were mostly consistent with the results of microarray. Cytokine analysis demonstrated that IL-27 and CXCL12 concentrations in responders were significantly higher than non-responders on the 3rd day after the first dose and 7th day after the second dose of vaccination, respectively. No significant difference was observed in other cytokine and chemokine signatures between the two groups. In conclusion, our results revealed characteristic transcriptome and cytokine changes in hepatitis B vaccine non-responders after boost immunization.
| S-EPMC6067885 | biostudies-other
Project description:The emergence of a vaccine against hepatitis B has proven to be an important milestone in the prevention of this disease; however, 5%–10% of vaccinated individuals do not generate an immune response to the vaccine, and its molecular mechanism has not been clarified. In this study, single-cell RNA sequencing was performed on peripheral blood mononuclear cells (PBMCs) from three volunteers with a high immune response (HR) and three with no immune response (NR) to the hepatitis B vaccine. We found that the antigenpresenting activity scores of various antigen-presenting cells, the mitogenactivated protein kinase (MAPK) pathway activity scores of naive B cells, and the cell activity scores of three types of effector T cells were significantly decreased, whereas the cytotoxicity scores of CD3highCD16lowKLRG1high natural killer T (NKT) cells were significantly increased in the NR group compared with those in the HR group. Additionally, the expression levels of some classical molecules associated with distinct signaling pathways—including HLA-B, HLA-DRB5, BLNK, BLK, IL4R, SCIMP, JUN, CEBPB, NDFIP1, and TXNIP— were significantly reduced in corresponding subsets of PBMCs from the NR group relative to those of the HR group. Furthermore, the expression of several cytotoxicity-related effector molecules, such as GNLY, NKG7, GZMB, GZMM, KLRC1, KLRD1, PRF1, CST7, and CTSW, was significantly higher in CD3highCD16lowKLRG1high NKT cells derived from non-responders. Our study provides a molecular basis for the lack of response to the hepatitis B vaccine, including defective antigen presentation, decreased T cell activity, and reduced IL-4 secretion, as well as novel insight into the role of NKT cells in the immune response to the hepatitis B vaccine.
2023-07-30 | GSE229431 | GEO
Project description:BackgroundHepatitis C virus (HCV) infects more than 71 million people worldwide and chronic HCV infection increases the risk of liver cirrhosis and failure. Haemodialysis (HD) is one of the renal replacement therapies with risk of HCV transmission. Anti-HCV antibodies are the serological screening test for HCV infection that does not detect active phase of infection. Majority HCV infected HD patients in Malaysia do not have further HCV RNA performed due to high cost and thus HCV treatment is less frequently offered. HCV Core Antigen (HCV Ag) can potentially be used to diagnose active HCV infection in HD population in comparison to HCV RNA, at lower cost.MethodsWe conducted a cross-sectional study to assess the correlation between HCV Ag and HCV RNA and to identify the prevalence of active HCV infection among HCV seropositive HD patients from dialysis centres across West Malaysia from July 2019 to May 2020. Pre-dialysis blood was taken and tested for both HCV Ag and HCV RNA tests. HCV Ag was tested with Abbott ARCHITECT HCV Ag test.ResultsWe recruited 112 seropositive HD patients from 17 centres with mean age of 54.04 ± 11.62 years, HD vintage of 14.1 ± 9.7 years, and male constitute 59.8% (67) of the study population. HCV Ag correlates well with HCV RNA (Spearman test coefficient 0.833, p < 0.001). The sensitivity was 90.7%, specificity 100%, positive predictive value (PPV) 100%, negative predictive value (NPV) 76.5%, and accuracy 92.9%. For HCV RNA level > 3000 IU/mL, HCV Ag had a higher sensitivity of 95.1% and greater correlation (Spearman test coefficient 0.897, p < 0.001). The prevalence of active HCV infection was 76.8% among HCV seropositive HD patients.ConclusionsAlthough HCV Ag is less sensitive, it shows an excellent correlation with HCV RNA and has 100% PPV. HCV Ag can be considered as an alternative diagnostic tool for chronic active HCV infection among HD cohort, who can then be considered for HCV treatment. For seropositive HD patient with negative HCV Ag, we recommend to follow-up with HCV RNA test.
| S-EPMC7666439 | biostudies-literature
Project description:To evaluate T cell immunity in advanced liver disease, antigen-specific lymphoproliferative (LP) responses were prospectively studied in the context of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis trial. Peripheral blood responses to hepatitis C virus (HCV), tetanus and Candida protein antigens were measured at baseline, month 12 (M12), M24, M36 and M48 in 186 patients randomized to either low-dose peginterferon-alfa-2a (PEG-IFN) only or observation. Liver histology was evaluated at baseline, M24 and M48. Patients with cirrhosis (Ishak 5-6) were less likely to have positive LP responses to HCV at baseline than patients with fibrosis (15%vs 29%, P = 0.03) and had lower levels of HCV c100 responses at baseline, M24 and M48 (P = 0.11, P = 0.05, P = 0.02, respectively). For 97 patients with complete longitudinal data, the frequency of positive LP responses to HCV, tetanus and Candida antigens declined over time (P < 0.003), and the slope of this decline was greater in the PEG-IFN treatment group than the observation group (P < 0.02). Lower levels of tetanus LP responses were associated with fibrosis progression and clinical outcomes (P = 0.009). Poorer CD4+ T cell proliferative function was associated with more advanced liver disease in chronic hepatitis C and may be further affected by long-term PEG-IFN treatment.
| S-EPMC3349971 | biostudies-literature
Project description:Background & aimsApproximately 5%-10% of the general population respond inadequately to licensed recombinant hepatitis B vaccines. We assessed the immunogenicity and safety of a new HBAI20 vaccine, consisting of a new AI20 adjuvant (20-µg recombinant human IL-2 attached to 20-µg aluminium hydroxide) in combination with HBVaxPro®-10 µg.MethodsIn a double-blinded, randomised, controlled phase 2 trial, 18- to 59-year-old healthy non-responders (titre <10 mIU/ml after three or more doses of hepatitis B vaccine) were assigned (3:1 ratio) to receive either HBAI20 vaccine or HBVaxPro®-10 µg in a 0, 1 and 2-month schedule. The primary outcome was seroprotection (titre ≥ 10 mIU/ml) measured 1-3 months following the third vaccination.ResultsA total of 133 participants were randomised to receive either HBAI20 vaccine (n = 101) or HBVaxPro®-10 µg (n = 32). In the modified intention-to-treat analysis, the seroprotection rate after the third vaccination was 92.0% (80/87) in the HBAI20 group and 79.3% (23/29) in the HBVaxPro®-10-µg group, P = .068. Using a generalised linear mixed model to adjust for stratification factors, a higher odds of seroprotection with HBAI20 vaccine was shown (adjusted odds ratio = 3.48, P = .028). Frequency of mild and moderate local adverse events was greater in the HBAI20 group than in the HBVaxPro®-10 µg. Rates of severe local adverse events and systemic adverse events were low and similar in both groups.ConclusionsIn this group of hepatitis B vaccine non-responders, the HBAI20 vaccine demonstrated a higher seroprotection rate when adjusting for stratification factors and a similar safety profile compared to the licensed recombinant HBVaxPro®-10 µg.
| S-EPMC8518051 | biostudies-literature
Project description:BackgroundNon-specific effect of acupuncture constitutes part of the overall effect generated via clinical encounter beyond needle insertion and stimulation. It is unclear how responders and non-responders of acupuncture experience non-specific effects differently. We aimed to compare their experiences in a nested qualitative study embedded in an acupuncture randomized trial on functional dyspepsia.MethodsPurposive sampling was used to capture experience of responders (n=15) and non-responders (n=15) to acupuncture via individual in-depth interviews. Design and analysis followed a framework analysis approach, with reference to an existing model on acupuncture non-specific effects. Themes emerging outside of this model were purposefully explored.ResultsResponders had a more trusting relationship with acupuncturist in response to their expression of empathy. In turn they were more actively engaged in lifestyle modifications and dietary advice offered by acupuncturists. Non-responders were not satisfied with the level of reassurance regarding acupuncture safety. They were also expecting more peer support from fellow participants, regarded that as an empowerment process for initiating and sustaining lifestyle changes.ConclusionsOur results highlighted key differences in acupuncture non-specific effect components experienced by responders and non-responders. Positive non-specific effects contributing to overall benefits could be enhanced by emphasizing on empathy expression from acupuncturists, trust-building, offering appropriate explanations on safety, and organizing patient support groups. Further research on the relative importance of each component is warranted.
| S-EPMC8503627 | biostudies-literature
Project description:Time series of gene expression arrays before and during treatment of Hepatitis C; days 0, 1, 2, 7, 14 and 28 for 69 participants (IDs 1 through 69 are used). Treating chronic hepatitis C using peginterferon alpha and ribavirin leads to sustained clearance of virus and clinical improvement in approximately 50% of patients. Response rates are lower among patients with genotype 1 than with genotypes 2 and 3 and among African American ( AA) compared to Caucasian (CA) patients. Using DNA microarrays, gene expression was assessed in a group of 33 African American and 36 Caucasian American patients with chronic hepatitis C, genotype 1 during the first 28 days of treatment. Results were examined with respect to treatment responses and to race. Patients showed a response to treatment at the gene expression level in RNA isolated from PBMC irrespective of degree of decrease in hepatitis C virus (HCV) RNA levels. However, gene expression responses were relatively blunted in patients with poor viral response (< 1.5 log10 IU/ml decrease at 28 days) compared to those in patients with a marked (> 3.5 log10 decrease) or intermediate (1.5 to 3.5 log10 decrease) response. The number of genes that were up- or down-regulated by peginterferon and ribavirin treatment was fewer in patients with a poor response compared to those with an intermediate or marked viral response. However AA patients had a stronger interferon response than CA patients in general. The induced levels of known ISGs such as OAS, MX1, IRF-7 and the toll like receptor TLR-7 was lower in poor response patients than in marked or intermediate response patients. Thus, the relative lack of viral response to interferon therapy of hepatitis C is associated with blunted interferon cell signaling. No specific regulatory gene could be identified as responsible for this global blunting or racial differences. Experiment Overall Design: Eligible patients were naïve to interferon and ribavirin treatment, had detectable HCV RNA in serum, and nearly all had a liver biopsy performed within the previous 18 months showing chronic hepatitis. Only patients who were born in the United States and designated themselves as âAfrican American/Blackâ or âCaucasian/Whiteâ were eligible. The clinical protocol called for participants to be treated for up to 48 weeks with peginterferon alpha-2a (Pegasysâ¢, Roche Pharmaceuticals Nutley, NJ) in a dose of 180 µg weekly by self-administered subcutaneous injection and ribavirin (Copegusâ¢, Roche) orally in a dose of 1000 or 1200 mg daily based on body weight of less than 75 kg or equal to or greater than 75 kg. Peripheral blood mononuclear cells (PBMC) were collected from patients before treatment (day 0) and on days 1 (after the initial supervised injection of peginterferon), 2, 7, 14 and 28. From the Virahep-C cohort, 72 patients who did not have dose reductions of either peginterferon or ribavirin in the first 28 days of treatment were selected such that 12 patients were included in each race (CA, AA) by virological response category. The three categories of response were: marked, defined as a decrease in HCV RNA levels of more than 3.5 log10 IU/ml or to undetectable on day 28; intermediate, defined as a decrease of 1.4 to 3.5 log10 IU/ml on day 28; and poor, defined as less than 1.4 log10 IU/ml decline on day 28 relative to baseline. These definitions were made a priori in an attempt to analyze the biological basis for virological responses. Of these, adequate RNA was not obtained from 3 patients to provide gene expression information. Of these 72, 69 were analyzed.
2008-06-16 | E-GEOD-7123 | biostudies-arrayexpress
Project description:Antigen-specific T cells play a major role in mediating the pathogenesis of a variety of autoimmune conditions as well as other diseases. In the context of experimental autoimmune encephalomyelitis, a murine model of multiple sclerosis, we present here a general approach to the discovery of highly specific ligands for autoreactive cells. These ligands are obtained from a combinatorial library of hundreds of thousands of synthetic peptoids that is screened simultaneously against two populations of CD4+ T cells. Peptoids that recognize autoreactive T cells with extremely high specificity can be identified in the library. Since no specific knowledge is required regarding the nature of the native antigens recognized by the autoreactive T cells, this technology provides a powerful tool for the enrichment and inhibition of autoimmune cells in a variety of disease states.
| S-EPMC2810551 | biostudies-literature