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Huang Y, Zhou W, Liu S, Zeng D, Zhou W. Association between polymorphisms and atopic dermatitis susceptibility: A systematic review and meta-analysis. Gene 2024; 913:148397. [PMID: 38513928 DOI: 10.1016/j.gene.2024.148397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Revised: 03/13/2024] [Accepted: 03/18/2024] [Indexed: 03/23/2024]
Abstract
AIM Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease that is closely linked to genetic factors. Previous studies have revealed numerous single nucleotide polymorphisms (SNPs) that been related to susceptibility to AD; however, the results are conflicting. Therefore, a meta-analysis was conducted to assess the associations of these polymorphisms and AD risk. MATERIAL AND METHODS PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure databases were retrieved to identify eligible studies, with selected polymorphisms being reported in a minimum of three separate studies. The Newcastle-Ottawa Scale (NOS) was used to evaluate study quality. Review Manager 5.3 and STATA 14.0 were used to perform the meta-analysis. RESULTS After screening, 64 studies involving 13 genes (24 SNPs) were selected for inclusion in the meta-analysis. Nine SNPs were positively correlated with AD susceptibility [filaggrin (FLG) R501X, FLG 2282del4, chromosome 11q13.5 rs7927894, interleukin (IL)-17A rs2275913, IL-18 -137 G/C, Toll-like receptor 2 (TLR2) rs5743708, TLR2 A-16934 T, serine protease inhibitor Kazal type-5 (SPINK5) Asn368Ser, interferon-γ (IFN-γ) T874A] and one was negatively associated with AD susceptibility (IL-4 -1098 T/G). The 14 remaining SNPs were not significantly associated with AD susceptibility. CONCLUSIONS Nine SNPs that may be risk factors and one SNP that may be a protective factor for AD were identified, providing a reference for AD prediction, prevention, and therapy.
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Affiliation(s)
- Yunxia Huang
- Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; Department of Allergy, Chongqing General Hospital, Chongqing 400014, China
| | - Wei Zhou
- Department of Allergy, Chongqing General Hospital, Chongqing 400014, China
| | - Shunan Liu
- Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; Department of Allergy, Chongqing General Hospital, Chongqing 400014, China
| | - Dan Zeng
- Department of Allergy, Chongqing General Hospital, Chongqing 400014, China
| | - Weikang Zhou
- Department of Dermatology, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; Department of Allergy, Chongqing General Hospital, Chongqing 400014, China.
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2
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Segbefia SP, Asandem DA, Amoah LE, Kusi KA. Cytokine gene polymorphisms implicated in the pathogenesis of Plasmodium falciparum infection outcome. Front Immunol 2024; 15:1285411. [PMID: 38404582 PMCID: PMC10884311 DOI: 10.3389/fimmu.2024.1285411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Accepted: 01/24/2024] [Indexed: 02/27/2024] Open
Abstract
Cytokines play a critical role in the immune mechanisms involved in fighting infections including malaria. Polymorphisms in cytokine genes may affect immune responses during an infection with Plasmodium parasites and immunization outcomes during routine administration of malaria vaccines. These polymorphisms can increase or reduce susceptibility to this deadly infection, and this may affect the physiologically needed balance between anti-inflammatory and pro-inflammatory cytokines. The purpose of this review is to present an overview of the effect of selected cytokine gene polymorphisms on immune responses against malaria.
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Affiliation(s)
- Selorm Philip Segbefia
- Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana
- Department of Molecular Medicine, School of Medicine and Dentistry, College of Science, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana
| | - Diana Asema Asandem
- Department of Virology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana
- West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, College of Basic and Applied Sciences, University of Ghana, Accra, Ghana
| | - Linda Eva Amoah
- Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana
- West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, College of Basic and Applied Sciences, University of Ghana, Accra, Ghana
| | - Kwadwo Asamoah Kusi
- Department of Immunology, Noguchi Memorial Institute for Medical Research, College of Health Sciences, University of Ghana, Accra, Ghana
- West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, College of Basic and Applied Sciences, University of Ghana, Accra, Ghana
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Qiu J, Zhang S, Feng Y, Su X, Cai J, Chen S, Liu J, Huang S, Huang H, Zhu S, Wen H, Li J, Yan H, Diao Z, Liang X, Zeng F. Efficacy and safety of hepatitis B vaccine: an umbrella review of meta-analyses. Expert Rev Vaccines 2024; 23:69-81. [PMID: 38055218 DOI: 10.1080/14760584.2023.2289566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2023] [Accepted: 11/27/2023] [Indexed: 12/07/2023]
Abstract
BACKGROUND There is a lack of synthesis of literature to determine hepatitis B vaccine (HepB) strategies for hepatitis B virus (HBV) supported by quality evidence. We aimed to explore the efficacy and safety of HepB strategies among people with different characteristics. RESEARCH DESIGN AND METHODS PubMed, Cochrane Library, Embase, and Web of Science were searched for meta-analyses comparing the efficacy and safety of HepB up to July 2023. RESULTS Twenty-one meta-analyses comparing 83 associations were included, with 16 high quality, 4 moderate, and 1 low quality assessed by AMSTAR 2. Highly suggestive evidence supports HepB booster and HepB with 1018 adjuvant (HBsAg-1018) for improved seroprotection, and targeted and universal HepB vaccination reduced HBV infection Suggestive evidence indicated that targeted vaccination decreased the rate of hepatitis B surface antibody positivity and booster doses increased seroprotection in people aged 10-20. Weak evidence suggests potential local/systemic reaction risk with nucleotide analogs or HBsAg-1018. Convincing evidence shows HLA-DPB1*04:01 and DPB1*04:02 increased, while DPB1*05:01 decreased, hepatitis B antibody response. Obesity may reduce HepB seroprotection, as highly suggested. CONCLUSION Targeted vaccination could effectively reduce HBV infection, and adjuvant and booster vaccinations enhance seroprotection without significant reaction. Factors such as obesity and genetic polymorphisms may affect the efficacy.
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Affiliation(s)
- Jiamin Qiu
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, PR China
| | - Shiwen Zhang
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, PR China
| | - Yonghui Feng
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, PR China
| | - Xin Su
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, PR China
| | - Jun Cai
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, PR China
| | - Shiyun Chen
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, PR China
| | - Jiazi Liu
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, PR China
| | - Shiqi Huang
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, PR China
| | - Haokun Huang
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, PR China
| | - Sui Zhu
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, PR China
| | - Huiyan Wen
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, PR China
| | - Jiaxin Li
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, PR China
| | - Haoyu Yan
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, PR China
| | - Zhiquan Diao
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, PR China
| | - Xiaofeng Liang
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, PR China
- Jinan University-BioKangtai Vaccine Institute, Jinan University, Shenzhen, China
| | - Fangfang Zeng
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou, PR China
- Jinan University-BioKangtai Vaccine Institute, Jinan University, Shenzhen, China
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Crouse B, Baehr C, Hicks D, Pravetoni M. IL-4 Predicts the Efficacy of a Candidate Antioxycodone Vaccine and Alters Vaccine-Specific Antibody-Secreting Cell Proliferation in Mice. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2023; 210:1272-1280. [PMID: 36939374 PMCID: PMC11321710 DOI: 10.4049/jimmunol.2200605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 02/27/2023] [Indexed: 03/21/2023]
Abstract
Opioid use disorders (OUDs) are a public health concern in the United States and worldwide. Current medications for OUDs may trigger side effects and are often heavily regulated. A novel treatment strategy to be used alone or in combination with existing medications is active immunization with antiopioid vaccines, which stimulate production of opioid-specific Abs that bind to the target drug and prevent its distribution to the brain. Although antiopioid vaccines have shown promising preclinical efficacy, prior clinical evaluations of vaccines targeting stimulants indicate that efficacy is limited to a subset of subjects who achieve optimal Ab responses. We have previously reported that depletion of IL-4 with a mAb increased opioid-specific IgG2a and total IgG, and it increased the number of germinal centers and germinal center T follicular helper cells in response to antiopioid vaccines via type I IL-4 signaling. The current study further investigates the mechanisms associated with IL-4-mediated increases in efficacy and whether IL-4 depletion affects specific processes involved in germinal center formation, including affinity maturation, class switching, and plasma cell differentiation in mice. Additionally, results demonstrate that preimmunization production of IL-4 after ex vivo whole blood stimulation predicted in vivo vaccine-induced Ab titers in outbred mice. Such mechanistic studies are critical for rational design of next-generation vaccine formulations, and they support the use of IL-4 as a predictive biomarker in ongoing OUD vaccine clinical studies.
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Affiliation(s)
- Bethany Crouse
- Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN
- School of Veterinary Population Medicine, University of Minnesota, St. Paul, MN
| | - Carly Baehr
- Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN
| | - Dustin Hicks
- Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN
| | - Marco Pravetoni
- Department of Pharmacology, University of Minnesota Medical School, Minneapolis, MN
- Center for Immunology, University of Minnesota, Minneapolis, MN
- Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA
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Di Lello FA, Martínez AP, Flichman DM. Insights into induction of the immune response by the hepatitis B vaccine. World J Gastroenterol 2022; 28:4249-4262. [PMID: 36159002 PMCID: PMC9453777 DOI: 10.3748/wjg.v28.i31.4249] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2022] [Revised: 05/21/2022] [Accepted: 07/25/2022] [Indexed: 02/06/2023] Open
Abstract
After more than four decades of hepatitis B virus (HBV) vaccine implementation, its safety and efficacy in preventing HBV infection have been proven and several milestones have been achieved. Most countries have included HBV immunization schedules in their health policies and progress has been made regarding universalization of the first HBV vaccine dose at birth. All of these actions have significantly contributed to reducing both the incidence of HBV infection and its related complications. However, there are still many drawbacks to overcome. The main concerns are the deficient coverage rate of the dose at birth and the large adult population that has not been reached timely by universal immunization. Additionally, the current most widely used second-generation vaccines do not induce protective immunity in 5% to 10% of the population, particularly in people over 40-years-old, obese (body mass index > 25 kg/m2), heavy smokers, and patients undergoing dialysis or infection with human immunodeficiency virus. Recently developed and approved novel vaccine formulations using more potent adjuvants or multiple antigens have shown better performance, particularly in difficult settings. These advances re-launch the expectations of achieving the World Health Organization’s objective of completing hepatitis control by 2030.
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Affiliation(s)
- Federico Alejandro Di Lello
- Microbiology, Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones en Bacteriología y Virología Molecular, Buenos Aires C1113AAD, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires C1425FQB, Argentina
| | - Alfredo Pedro Martínez
- Virology Section, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno “CEMIC”, Buenos Aires C1431FWO, Argentina
| | - Diego Martín Flichman
- Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires C1425FQB, Argentina
- Microbiology, Universidad de Buenos Aires, Instituto de Investigaciones Biomédicas en Retrovirus y Síndrome de Inmunodeficiencia Adquirida, Buenos Aires C1121ABG, Argentina
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Folic acid supplementation in pregnant women with hepatitis B surface antigen improves infant hepatitis B surface antibody mediated by infant IL-4. Br J Nutr 2022; 129:1812-1819. [PMID: 35872569 DOI: 10.1017/s000711452200229x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Immunoprophylaxis has not completely eliminated hepatitis B virus (HBV) infection due to hyporesponsiveness to hepatitis B vaccine (HepB). We explored the impact of folic acid supplementation (FAS) in pregnant women with positive hepatitis B surface antigen (HBsAg) on their infant hepatitis B surface antibody (anti-HBs) and the mediation effect of infant interleukin-4 (IL-4). We recruited HBsAg-positive mothers and their neonates at baseline. Maternal FAS was obtained via a questionnaire, and neonatal anti-HBs and IL-4 were detected. Follow-up was performed at 11-13 months of age of infants, when anti-HBs and IL-4 were measured. We applied univariate and multivariate analyses. A mediation effect model was performed to explore the mediating role of IL-4. A total of 399 mother-neonate pairs were enrolled and 195 mother-infant pairs were eligible for this analysis. The infant anti-HBs geometric mean concentrations in the maternal FAS group were significnatly higher than those in the no-FAS group (383·8 mIU/ml, 95 % CI: 294·2 mIU/ml to 500·7 mIU/ml v. 217·0 mIU/ml, 95 % CI: 147·0 mIU/ml to 320·4 mIU/ml, z = -3·2, P = 0·001). Infants born to women who took folic acid (FA) within the first trimester were more likely to have high anti-HBs titres (adjusted β-value = 194·1, P = 0·003). The fold change in IL-4 from neonates to infants partially mediated the beneficial influence of maternal FAS on infant anti-HBs (24·7 % mediation effect) after adjusting for confounding factors. FAS during the first trimester to HBsAg-positive mothers could facilitate higher anti-HBs levels in infants aged 11-13 months partly by upregulating IL-4 in infants.
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Trevisan A, Mason P, Nicolli A, Maso S, Fonzo M, Scarpa B, Bertoncello C. Future Healthcare Workers and Hepatitis B Vaccination: A New Generation. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18157783. [PMID: 34360071 PMCID: PMC8345783 DOI: 10.3390/ijerph18157783] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 07/08/2021] [Accepted: 07/21/2021] [Indexed: 12/19/2022]
Abstract
Before the introduction of universal vaccination, hepatitis B caused high morbidity and mortality, especially among healthcare workers. In the present study, the immune status against hepatitis B was assessed in a cohort of 11,188 students of the degree courses of the School of Medicine of the University of Padua (Italy) who had been subjected to mandatory vaccination in childhood or adolescence and who will be future healthcare workers. The variables that influence the antibody response to vaccination are mainly the age at which the vaccine was administered and sex. If vaccination was administered before one year of age, there is a high probability (around 50%) of having an antibody titer lower than 10 IU/L compared to those vaccinated after one year of age (12.8%). The time between vaccine and analysis is not decisive. Furthermore, female sex, but only if vaccination was administered after one year of age, shows a significant (p = 0.0008) lower percentage of anti-HBs below 10 IU/L and a greater antibody titer (p < 0.0001). In conclusion, the differences related to the age of vaccination induce more doubts than answers. The only plausible hypothesis, in addition to the different immune responses (innate and adaptive), is the type of vaccine. This is not easy to verify because vaccination certificates rarely report it.
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Affiliation(s)
- Andrea Trevisan
- Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy; (P.M.); (A.N.); (S.M.); (M.F.); (C.B.)
- Correspondence:
| | - Paola Mason
- Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy; (P.M.); (A.N.); (S.M.); (M.F.); (C.B.)
| | - Annamaria Nicolli
- Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy; (P.M.); (A.N.); (S.M.); (M.F.); (C.B.)
| | - Stefano Maso
- Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy; (P.M.); (A.N.); (S.M.); (M.F.); (C.B.)
| | - Marco Fonzo
- Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy; (P.M.); (A.N.); (S.M.); (M.F.); (C.B.)
| | - Bruno Scarpa
- Department of Statistical Sciences, University of Padova, 35128 Padova, Italy;
| | - Chiara Bertoncello
- Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy; (P.M.); (A.N.); (S.M.); (M.F.); (C.B.)
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Zhang Z, Wang C, Liu Z, Zou G, Li J, Lu M. Host Genetic Determinants of Hepatitis B Virus Infection. Front Genet 2019; 10:696. [PMID: 31475028 PMCID: PMC6702792 DOI: 10.3389/fgene.2019.00696] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 07/03/2019] [Indexed: 12/14/2022] Open
Abstract
Chronic hepatitis B virus (HBV) infection is still a major health problem worldwide. Recently, a great number of genetic studies based on single nucleotide polymorphisms (SNPs) and genome-wide association studies have been performed to search for host determinants of the development of chronic HBV infection, clinical outcomes, therapeutic efficacy, and responses to hepatitis B vaccines, with a focus on human leukocyte antigens (HLA), cytokine genes, and toll-like receptors. In addition to SNPs, gene insertions/deletions and copy number variants are associated with infection. However, conflicting results have been obtained. In the present review, we summarize the current state of research on host genetic factors and chronic HBV infection, its clinical type, therapies, and hepatitis B vaccine responses and classify published results according to their reliability. The potential roles of host genetic determinants of chronic HBV infection identified in these studies and their clinical significance are discussed. In particular, HLAs were relevant for HBV infection and pathogenesis. Finally, we highlight the need for additional studies with large sample sizes, well-matched study designs, appropriate statistical methods, and validation in multiple populations to improve the treatment of HBV infection.
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Affiliation(s)
- Zhenhua Zhang
- Department of Infectious Diseases, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
- College of Pharmacy, Anhui Medical University, Hefei, China
| | - Changtai Wang
- Department of Infectious Diseases, the Affiliated Anqing Hospital of Anhui Medical University, Anqing, China
| | - Zhongping Liu
- Department of Infectious Diseases, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Guizhou Zou
- Department of Infectious Diseases, the Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Jun Li
- College of Pharmacy, Anhui Medical University, Hefei, China
| | - Mengji Lu
- Institute of Virology, University Hospital of Duisburg-Essen, Essen, Germany
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Gu Y, Lian Y, Gu L, Chen L, Li X, Zhou L, Huang Y, Wang J, Huang Y. Correlations between cytokines produced by T cells and clinical-virological characteristics in untreated chronic hepatitis B patients. BMC Infect Dis 2019; 19:216. [PMID: 30832595 PMCID: PMC6398217 DOI: 10.1186/s12879-019-3853-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2017] [Accepted: 02/26/2019] [Indexed: 12/13/2022] Open
Abstract
Background Hepatitis B virus (HBV) replicates non-cytopathically in the hepatocytes and HBV-related diseases are caused by immune-mediated inflammatory events. This study aimed to identify the relationship between clinical-virological characteristics and immunity in untreated chronic hepatitis B (CHB) patients. Methods A total of 209 CHB patients were categorized into immune tolerant (IT, n = 17), inactive carrier (IC, n = 20), immune active (IA, n = 120), and gray zone (GZ, n = 72) phases. The quantitative hepatitis B surface antigen (qHBsAg), hepatitis B e antigen (HBeAg), anti-HBeAg (HBeAb), HBV genotype, viral mutant and frequencies of interleukin (IL)-4, IL-17, IL-10 and interferon-gamma (IFN-γ) produced by CD4+ and CD8+ T cells were tested. We also correlated these cytokines with clinical-virological characteristics using a linear regression model. Results CD8+ T cells frequency were significantly decreased in IT patients. Levels of CD4+ T cells IL-4+ or IL-10+ were strongly negatively associated with qHBsAg titers. The frequency of IFN-γ produced by CD4+ and CD8+ T cells showed significant positive association with age and alanine aminotransferase (ALT) level, while that had negative association with qHBsAg titers. Additionally, the ratios of mutations in the HBV precore (PC) stop codon and basal core promoter (BCP) and the combined mutations were 32.5, 27.2, and 11.3%, respectively. The frequency of CD4+ T cells IL-17+ was higher in patients with a PC mutation than that in patients carrying a wild-type sequence. Finally, little associations among T cell derived IL-4, IL-10, IL-17, and IFN-γ was observed in the current untreated CHB cohort. Conclusions Several components of the immune system were correlated with HBV factors that influence an inflammatory process during CHB. Of particular relevance are the significant associations of between CD4+ T cells IL-4+ and qHBsAg level, and between CD4+ T cells IL-17+ and the presence of a mutation in PC.
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Affiliation(s)
- Yurong Gu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tian He Rd., Guangzhou, 510630, China
| | - Yifan Lian
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lin Gu
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Lubiao Chen
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tian He Rd., Guangzhou, 510630, China
| | - Xiaoyan Li
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tian He Rd., Guangzhou, 510630, China
| | - Liang Zhou
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tian He Rd., Guangzhou, 510630, China
| | - Yanlin Huang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tian He Rd., Guangzhou, 510630, China
| | - Jialiang Wang
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yuehua Huang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tian He Rd., Guangzhou, 510630, China. .,Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
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10
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Liang J, Liu Y, Xue R, Chen L, Chen H, Shao L, Wang J, Zhang X. Interleukin 4 –590C/T (rs2243250) Polymorphism Is Associated With Increased Risk of Atopic Dermatitis: Meta-Analysis of Case-Control Studies. Dermatitis 2017; 28:144-151. [DOI: 10.1097/der.0000000000000265] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
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Rolland M, Eller M. Systems Vaccinology. HUMAN VACCINES 2017. [DOI: 10.1016/b978-0-12-802302-0.00004-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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12
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Roh EY, Song EY, Yoon JH, Oh S, Chang JY, Park H, Seo SH, Shin S. Effects of interleukin-4 and interleukin-12B gene polymorphisms on hepatitis B virus vaccination. Ann Hepatol 2017; 16:63-70. [PMID: 28051794 DOI: 10.5604/16652681.1226816] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Approximately 10% of individuals do not respond to hepatitis B virus (HBV) vaccination, i.e. non-responders (NRs). We aimed to investigate the association of interleukin (IL)-4 and IL-12B gene polymorphisms with responsiveness to the HBV vaccine in Korean infants. Among 300 healthy infants (9-12 month), SNPs for the IL-4 gene (rs2243250, rs2070874, and rs2227284) and for the IL-12B gene (rs3213094 and rs17860508) were compared between subgroups in terms of the response to HBV vaccination. The percentages of NRs (< 10 mIU/mL), low-titer responders (LRs, 10-100 mIU/mL), and high-titer responders (HRs, ≥ 100 mIU/mL) were 20.3%, 37.7% and 42.0%, respectively. No SNPs differed in frequency between NRs and responders or between LRs and HRs. We divided the subjects into two groups according to the time interval from the 3rd dose of HBV vaccination to Ab quantification: > 6 months from the 3rd dose (n = 87) and ≤ 6 months from the 3rd dose (n = 213). In the ≤ 6 month subjects, rs2243250C and rs2227284G were significantly frequent in the lower-titer individuals (NRs + LR) than HRs (40.1 vs. 25.9%, p = 0.014 and 45.1 vs. 33.0%, p = 0.018, respectively), and the rs2243250C and rs2227284G frequencies were significantly different among the three subgroups (13.2 vs. 26.9 vs. 25.9%, p = 0.040 and 15.5 vs. 29.6 vs. 33.0%, p = 0.038, respectively). In conclusion, those results suggest that IL-4 gene polymorphisms may play a role in the response to the HBV vaccine in Korean infants.
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Affiliation(s)
- Eun Youn Roh
- Department of Laboratory Medicine, Seoul National University Boramae Medical Center, Seoul, Korea
| | - Eun Young Song
- Eun Youn Roh and Eun Young Song contributed equally to this study as co-first authors
| | - Jong Hyun Yoon
- Department of Laboratory Medicine, Seoul National University Boramae Medical Center, Seoul, Korea
| | - Sohee Oh
- Department of Biostatistics, Seoul National University Boramae Medical Center, Seoul, Korea
| | - Ju Young Chang
- Department of Pediatrics, Seoul National University Boramae Medical Center, Seoul, Korea
| | - Hyunwoong Park
- Department of Laboratory Medicine, Gyeongsang National University College of Medicine, Jinju, Korea
| | - Soo Hyun Seo
- Department of Laboratory Medicine, Seoul National University Boramae Medical Center, Seoul, Korea
| | - Sue Shin
- Department of Laboratory Medicine, Seoul National University Boramae Medical Center, Seoul, Korea
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13
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Van Der Meeren O, Peterson JT, Dionne M, Beasley R, Ebeling PR, Ferguson M, Nissen MD, Rheault P, Simpson RW, De Ridder M, Crasta PD, Miller JM, Trofa AF. Prospective clinical trial of hepatitis B vaccination in adults with and without type-2 diabetes mellitus. Hum Vaccin Immunother 2016; 12:2197-2203. [PMID: 27123743 PMCID: PMC4994745 DOI: 10.1080/21645515.2016.1164362] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Objective: Patients with diabetes mellitus are at increased risk for hepatitis B virus (HBV) infection and its complications. HBV vaccination is recommended for adults with diabetes in the United States and other countries. However, few studies have assessed safety and immunogenicity of hepatitis B vaccine in such patients. We assessed the safety and immunogenicity of recombinant hepatitis B vaccine in subjects with and without diabetes mellitus. Methods: Prospective, multi-country controlled study in 21 centers (www.clinicaltrials.gov NCT01627340). Four hundred and sixteen participants with Type-2 diabetes and 258 controls matched for age and body mass index (BMI) (2:1 ratio) received 3-doses of HBV vaccine (Engerix-B™, GSK Vaccines, Belgium) according to a 0, 1, 6 months schedule. Antibodies were measured against HBV surface antigen and expressed as seroprotection rates (anti-HBs ≥10mIU/mL) and geometric mean concentration (GMC). Results: The median age and BMI in patients with diabetes and controls (according-to-protocol cohort) were 54 y and 32.1 kg/m2, and 53 y and 30.8 kg/m2, respectively. Seroprotection rates (GMCs) one month post-dose-3 were 75.4% (147.6 mIU/mL) and 82.0% (384.2 mIU/mL) in patients with diabetes and controls, respectively. Age-stratified seroprotection rates for patients with diabetes were 88.5% (20–39 years), 81.2% (40–49 years), 83.2% (50–59 years), and 58.2% (≥60 years). The overall safety profile of hepatitis B vaccine was similar between groups. Conclusions: Hepatitis B vaccine is immunogenic in patients with diabetes and has a similar safety profile to vaccination in healthy controls. Because increasing age was generally associated with a reduction in seroprotection rates, hepatitis B vaccine should be administered as soon as possible after the diagnosis of diabetes.
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Affiliation(s)
- Olivier Van Der Meeren
- a Eastern Clinical Research Unit, Department of Medicine , Monash University, and Eastern Health , Box Hill, Victoria , Australia
| | | | - Marc Dionne
- c Centre Hospitalier Universitaire , Quebec , Canada
| | - Richard Beasley
- d Medical Research Institute of New Zealand , Wellington , New Zealand
| | - Peter R Ebeling
- e Department of Medicine, School for Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences , Monash University , Victoria , Australia
| | | | - Michael D Nissen
- g Queensland Paediatric Infectious Diseases Laboratory, Queensland Children's Medical Research Institute , University of Queensland , Herston , Queensland , Australia.,h GSK Vaccines , Singapore
| | | | - Richard W Simpson
- j Eastern Clinical Research Unit, Department of Medicine , Monash University, and Eastern Health , Box Hill , Victoria , Australia
| | - Marc De Ridder
- a Eastern Clinical Research Unit, Department of Medicine , Monash University, and Eastern Health , Box Hill, Victoria , Australia.,k Faculté de Pharmacie , Université Libre de Bruxelles , Bruxelles , Belgium
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14
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Salehi M, Haghighat A, Salehi H, Taleban R, Salehi M, Kalbasi N, Moafi M, Salehi MM. Effect of tetanus-diphtheria (Td) vaccine on immune response to hepatitis B vaccine in healthy individuals with insufficient immune response. JOURNAL OF RESEARCH IN MEDICAL SCIENCES 2016; 20:958-62. [PMID: 26929760 PMCID: PMC4746869 DOI: 10.4103/1735-1995.172784] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Background: Hepatitis B virus (HBV) fails to produce appropriate immune responses in some healthy individuals; thus, different strategies have been adopted to promote immune responses. The current study aimed at evaluating the efficacy of HBV vaccine coadministered with tetanus-diphtheria (Td) vaccine compared with HBV vaccine in healthy individuals through measuring hepatitis B surface antibody (HBsAb) levels. Materials and Methods: This was a randomized controlled clinical trial, which was implemented in Isfahan, Isfahan Province (Iran) in 2013. One hundred and forty healthy individuals, whose HBsAb titers were less than 10 IU/L were recruited. The subjects were randomly assigned to either in intervention or control trials. The control group received 40 μg of recombinant HBV vaccines intramuscularly injected at 0, 1, and 6 months; however, the intervention group was simultaneously vaccinated by Td with the first dose of HBV vaccine. HBV antibody levels (titer) were measured before the vaccination and 6 months after the last vaccination. Results: Antibody titers of the subjects in the intervention and control groups increased from 5.07 ± 2.9 IU/L to 744.45 ± 353.07 IU/L and from 4.45 ± 3.4 IU/L to 589.94 ± 353 IU/L, respectively (both P < 0.001). Also, the mean difference of antibody titer was significantly different between the two groups (P = 0.011). Conclusion: Td vaccination can be applied as a feasible approach to promote efficient and persistent immunity in healthy individuals with insufficient HBsAb titers.
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Affiliation(s)
- Maryam Salehi
- Student Research Committee, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Abbas Haghighat
- Department of Oral Surgery, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Hassan Salehi
- Infectious Diseases and Tropical Medicine Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Roya Taleban
- Department of Community Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Marzieh Salehi
- Student Research Committee, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Nader Kalbasi
- Department of Pathology, School of Dentistry, Islamic Azad University (Khorasgan Branch), Isfahan, Iran
| | - Mohammad Moafi
- Acquired Immunodeficiency Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Mahdi Salehi
- Student Research Committee, School of Dentistry, Isfahan University of Medical Sciences, Isfahan, Iran
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15
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Wu Z, Qin W, Zeng J, Huang C, Lu Y, Li S. Association Between IL-4 Polymorphisms and Risk of Liver Disease: An Updated Meta-Analysis. Medicine (Baltimore) 2015; 94:e1435. [PMID: 26334904 PMCID: PMC4616498 DOI: 10.1097/md.0000000000001435] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Interleukin-4 (IL-4) polymorphisms have been reported to influence an individual's susceptibility to liver disease as it is a central anti-inflammatory Th2 cytokine; however, these results remain controversial.A comprehensive meta-analysis of the relevant literature was thus performed to better estimate the relationship between IL-4 polymorphisms and liver disease.Systematic searches of various databases (PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure) for studies published before July 5, 2015 were performed. Odds ratios (ORs) with 95% confidence intervals (CIs) calculated in fixed or random-effects models were used to estimate the strength of the association. Subgroup analyses, meta-regression, Galbraith plots, and sensitivity analyses were also performed.A total of 16 case-control studies, of which 15 involved the -590C/T polymorphism and 3 involved the -33T/C polymorphism, were included in the study. With respect to the -590C/T polymorphism, a significantly increased risk of liver diseases was found in the overall population (TT + CT vs CC: OR = 1.25, 95% CI = 1.06-1.49, P = 0.009 and CT vs CC: OR = 1.22, 95% CI = 1.00-1.48, P = 0.048) and the Asian population (TT + CT vs CC: OR = 1.28, 95% CI = 1.04-1.57, P = 0.020). Further subgroup analyses also showed significant associations between the -590C > T polymorphism and the risk of hepatitis C infection and hepatocellular carcinoma. However, no association was found between the -33T/C polymorphism and risk of liver diseases in all comparison models.This meta-analysis suggested that the IL-4 -590C > T polymorphism is associated with an increased risk of hepatitis C infection and hepatocellular carcinoma, especially among the Asian population.
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Affiliation(s)
- Zhitong Wu
- From the Department of Clinical Laboratory, Guigang People's Hospital, Guigang, Guangxi, China (ZW, WQ); Department of Clinical Laboratory, Liuzhou City People's Hospital, Liuzhou, Guangxi, China (JZ); and Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China (CH, YL, SL)
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16
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Correlation of an interleukin-4 gene polymorphism with susceptibility to severe enterovirus 71 infection in Chinese children. Arch Virol 2015; 160:1035-42. [PMID: 25666199 DOI: 10.1007/s00705-015-2356-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2014] [Accepted: 01/29/2015] [Indexed: 10/24/2022]
Abstract
Enterovirus 71 (EV71) has caused many outbreaks of diseases among children worldwide since it was first reported in 1974, but its mechanism of pathogenesis remains unclear. This study was designed to investigate the possible association of the IL-4 -589C/T gene polymorphism with severity of EV71 infection in Chinese children. The IL-4 -589C/T gene polymorphism was detected in EV71-infected subjects (n = 185), including those with mild cases (n = 102) and severe cases (n = 83) as well as healthy controls (n = 234), using an improved multiplex ligation detection reaction (iMLDR) technique. The plasma levels of IL-4 and IFN-γ were determined by enzyme-linked immunosorbent assays. The presence of the CC genotype (p = 0.022) and the C allele (OR, 2.1; 95 % CI, 1.3-3.6; p = 0.004) was significantly higher in severe cases. Furthermore, the CC genotype and C allele were also more frequently found in cases of EV71 encephalitis (p < 0.05). The plasma levels of IL-4 of the CC (7.9 ± 1.3 pg/mL, p < 0.001) and CT genotype (6.8 ± 2.1 pg/mL, p < 0.01) were significantly elevated compared to those of the TT genotype, but the plasma levels of IFN-γ and the IFN-γ/IL-4 ratio were significantly lower for the CC and CT genotypes than for the TT genotype (p < 0.05). These findings suggest that the IL-4 -589C allele could be a susceptibility factor in the development of EV71 disease in Chinese children.
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17
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Newport MJ. The genetic regulation of infant immune responses to vaccination. Front Immunol 2015; 6:18. [PMID: 25699041 PMCID: PMC4313718 DOI: 10.3389/fimmu.2015.00018] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2014] [Accepted: 01/09/2015] [Indexed: 12/16/2022] Open
Abstract
A number of factors are recognized to influence immune responses to vaccinations including age, gender, the dose, and quality of the antigen used, the number of doses given, the route of administration, and the nutritional status of the recipient. Additionally, several immunogenetic studies have identified associations between polymorphisms in genes encoding immune response proteins, both innate and adaptive, and variation in responses to vaccines. Variants in the genes encoding Toll-like receptors, HLA molecules, cytokines, and cytokine receptors have associated with heterogeneity of responses to a wide range of vaccines including measles, hepatitis B, influenza A, BCG, Haemophilus influenzae type b, and certain Neisseria meningitidis serotypes, amongst others. However, the vast majority of these studies have been conducted in older children and adults and there are very few data available from studies conducted in infants. This paper reviews the evidence to date that host genes influencing vaccines responses in these older population and identifies a large gap in our understanding of the genetic regulation of responses in early life. Given the high mortality from infection in early life and the challenges of developing vaccines that generate effective immune responses in the context of the developing immune system further research on infant populations is required.
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Affiliation(s)
- Melanie J. Newport
- Division of Clinical Medicine, Brighton and Sussex Medical School, Brighton, UK
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18
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Trevisan A, Nicolli A, Chiara F. Hepatitis B: prevention, protection and occupational risk. Future Virol 2015. [DOI: 10.2217/fvl.14.90] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
ABSTRACT Since 1992, the inclusion of HBV vaccination has been recommended by the WHO for all immunization programs implemented by nations. In Europe, the introduction of HBV vaccination has markedly reduced the incidence of acute HBV, and before the introduction of HBV vaccine, healthcare workers (HCW) were at considerable risk of infection. The present review discusses the main problems regarding three fundamental issues in hospital settings: prevention of HBV in HCW, protection induced by vaccination (problems regarding nonresponders) and risk for HCW exposed to blood-borne pathogens (occupational risk). The screening of HBV markers plays a decisive role in evaluating the degree of immune coverage in subjects exposed to biological risk and permits an increase in immune coverage through vaccine implementation.
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Affiliation(s)
- Andrea Trevisan
- Department of Cardiologic, Thoracic & Vascular Sciences, University of Padova, Via Giustiniani 2, I-35128 Padova, Italy
| | - Annamaria Nicolli
- Department of Cardiologic, Thoracic & Vascular Sciences, University of Padova, Via Giustiniani 2, I-35128 Padova, Italy
| | - Federica Chiara
- Department of Cardiologic, Thoracic & Vascular Sciences, University of Padova, Via Giustiniani 2, I-35128 Padova, Italy
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19
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Egli A, Santer DM, O'Shea D, Barakat K, Syedbasha M, Vollmer M, Baluch A, Bhat R, Groenendyk J, Joyce MA, Lisboa LF, Thomas BS, Battegay M, Khanna N, Mueller T, Tyrrell DLJ, Houghton M, Humar A, Kumar D. IL-28B is a key regulator of B- and T-cell vaccine responses against influenza. PLoS Pathog 2014; 10:e1004556. [PMID: 25503988 PMCID: PMC4263767 DOI: 10.1371/journal.ppat.1004556] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2014] [Accepted: 11/05/2014] [Indexed: 12/11/2022] Open
Abstract
Influenza is a major cause of morbidity and mortality in immunosuppressed persons, and vaccination often confers insufficient protection. IL-28B, a member of the interferon (IFN)-λ family, has variable expression due to single nucleotide polymorphisms (SNPs). While type-I IFNs are well known to modulate adaptive immunity, the impact of IL-28B on B- and T-cell vaccine responses is unclear. Here we demonstrate that the presence of the IL-28B TG/GG genotype (rs8099917, minor-allele) was associated with increased seroconversion following influenza vaccination (OR 1.99 p = 0.038). Also, influenza A (H1N1)-stimulated T- and B-cells from minor-allele carriers showed increased IL-4 production (4-fold) and HLA-DR expression, respectively. In vitro, recombinant IL-28B increased Th1-cytokines (e.g. IFN-γ), and suppressed Th2-cytokines (e.g. IL-4, IL-5, and IL-13), H1N1-stimulated B-cell proliferation (reduced 70%), and IgG-production (reduced>70%). Since IL-28B inhibited B-cell responses, we designed antagonistic peptides to block the IL-28 receptor α-subunit (IL28RA). In vitro, these peptides significantly suppressed binding of IFN-λs to IL28RA, increased H1N1-stimulated B-cell activation and IgG-production in samples from healthy volunteers (2-fold) and from transplant patients previously unresponsive to vaccination (1.4-fold). Together, these findings identify IL-28B as a key regulator of the Th1/Th2 balance during influenza vaccination. Blockade of IL28RA offers a novel strategy to augment vaccine responses.
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Affiliation(s)
- Adrian Egli
- Infection Biology, Department of Biomedicine, University of Basel, Basel, Switzerland
- Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada
| | - Deanna M. Santer
- Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada
| | - Daire O'Shea
- Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada
- Division of Infectious Diseases, University of Alberta, Edmonton, Alberta, Canada
| | - Khaled Barakat
- Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada
- Faculty of Pharmacy, University of Alberta, Canada
| | | | - Madeleine Vollmer
- Infection Biology, Department of Biomedicine, University of Basel, Basel, Switzerland
| | - Aliyah Baluch
- Division of Infectious Diseases, Moffitt Cancer Center, Tampa, Florida, United States of America
| | - Rakesh Bhat
- Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada
| | - Jody Groenendyk
- Department of Biochemistry, School of Translational Medicine, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada
| | - Michael A. Joyce
- Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada
| | - Luiz F. Lisboa
- Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada
| | - Brad S. Thomas
- Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada
| | - Manuel Battegay
- Infection Biology, Department of Biomedicine, University of Basel, Basel, Switzerland
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Basel, Switzerland
| | - Nina Khanna
- Infection Biology, Department of Biomedicine, University of Basel, Basel, Switzerland
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Basel, Switzerland
| | - Thomas Mueller
- Division of Nephrology, University Hospital of Zurich, Zurich, Switzerland
| | - D. Lorne J. Tyrrell
- Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada
| | - Michael Houghton
- Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta, Canada
| | - Atul Humar
- Department of Medicine and Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
| | - Deepali Kumar
- Department of Medicine and Multi-Organ Transplant Program, University Health Network, Toronto, Ontario, Canada
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20
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Lu Y, Wu Z, Peng Q, Ma L, Zhang X, Zhao J, Qin X, Li S. Role of IL-4 gene polymorphisms in HBV-related hepatocellular carcinoma in a Chinese population. PLoS One 2014; 9:e110061. [PMID: 25295591 PMCID: PMC4190355 DOI: 10.1371/journal.pone.0110061] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2014] [Accepted: 09/08/2014] [Indexed: 12/16/2022] Open
Abstract
Background Interleukin-4 (IL-4) is best known as an important mediator and modulator of immune and inflammatory responses. Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer, and genetic variations in the IL-4 gene may be associated with the risk of hepatitis B virus (HBV)-related HCC. However, few studies have been conducted on their association. Objectives To clarify the effects of IL-4 gene polymorphisms on the risk of HBV-related HCC, two common variants, −590C/T (rs2243250) and −33C/T (rs2070874), and their relationship with HBV-related disease risk were investigated in a Chinese population. Methods IL-4 −590C/T and −33C/T polymorphisms were examined in 154 patients with HBV-related HCC, 62 patients with HBV-induced liver cirrhosis (LC), 129 patients with chronic hepatitis B (CHB), and 94 healthy controls, using the polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing. Results Overall, no significant differences were observed regarding the IL-4 −590C/T and −33C/T polymorphism genotypes, alleles, or haplotypes between the patient groups and the healthy controls. However, the CC genotypes of IL-4 −590C/T and −33C/T polymorphisms were observed to be significantly associated with CHB in subgroup analysis in males [CC versus TT (OR: 4.193, 95% CI: 1.094–16.071, P = 0.037; and OR: 3.438, 95% CI: 1.032–11.458, P = 0.044) and CC versus TT+CT (OR: 4.09, 95% CI: 1.08–15.49, P = 0.038; and OR: 3.43, 95% CI: 1.04–11.28, P = 0.042)]. Conclusions These findings suggest that genetic variants in IL-4 −590C/T and −33C/T polymorphisms may be a risk factor for CHB in Chinese males but not for HBV-related LC or HCC.
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Affiliation(s)
- Yu Lu
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Zhitong Wu
- Department of Clinical Laboratory, Guigang People’s Hospital, Guigang, Guangxi, China
| | - Qiliu Peng
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Liping Ma
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Xiaolian Zhang
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Jiangyang Zhao
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
| | - Xue Qin
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- * E-mail: (XQ); (SL)
| | - Shan Li
- Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China
- * E-mail: (XQ); (SL)
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