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Marjani A, Alavian SM, Nassiri Toosi M, Alavian SH, Abazari MF, Khamseh A, Jazayeri SM. Hepatitis B virus infection after immunization: How serious it is? An updated review. Clin Exp Med 2025; 25:113. [PMID: 40210771 PMCID: PMC11985588 DOI: 10.1007/s10238-025-01645-8] [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: 01/03/2025] [Accepted: 03/19/2025] [Indexed: 04/12/2025]
Abstract
Infection with hepatitis B virus (HBV) is one of the significant challenges worldwide. Despite the availability of antiviral drugs against this virus, the most critical strategy to prevent HBV infection is HB vaccination. Basically, despite widespread conventional HB vaccination, due to various reasons, including waning of hepatitis B surface antibody (HBsAb) titer after vaccination, the emergence of vaccine-escape mutants, failure to respond to the vaccine due to viral and host factors, levels of response in high-risk individuals and non-responders to conventional HB vaccination remains a major, unsolved and severe concern. This review focuses on the underlying reasons for conventional hepatitis B vaccination failures. It also suggests solutions to overcome these failures by highlighting significant advances in vaccination, including hepatitis B third-generation vaccines and adjuvanted hepatitis B vaccines as efficient alternatives to second-generation vaccines. Potentially, these new strategies will compensate for the shortcomings caused by second-generation vaccines. Adherence to these denouements has a significant role in preventing the circulation of HBV among individuals and reducing the global burden of HBV-related diseases.
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Affiliation(s)
- Arezoo Marjani
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mohssen Nassiri Toosi
- Liver Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Mohammad Foad Abazari
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
- Division of Medical Sciences, Island Medical Program, University of British Columbia, Victoria, BC, Canada
| | - Azam Khamseh
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Science, Shiraz, Iran
| | - Seyed Mohammad Jazayeri
- Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran.
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Asri N, Mohammadi S, Jahdkaran M, Rostami-Nejad M, Rezaei-Tavirani M, Mohebbi SR. Viral infections in celiac disease: what should be considered for better management. Clin Exp Med 2024; 25:25. [PMID: 39731690 DOI: 10.1007/s10238-024-01542-6] [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: 11/26/2024] [Accepted: 12/20/2024] [Indexed: 12/30/2024]
Abstract
Following a gluten-free diet (GFD) is known as the main effective therapy available for celiac disease (CD) patients, which in some cases is not enough to heal all patients presentations completely. Accordingly, emerging researchers have focused on finding novel therapeutic/preventive strategies for this disorder. Moreover, previous studies have shown that celiac patients, especially untreated subjects, are at increased risk of developing viral and bacterial infections, which can become a challenge for the clinician. Viruses, such as Rotavirus, Reovirus, Adenovirus, Enterovirus, Rhinovirus, Astrovirus, Hepatitis virus, COVID-19, Norovirus, and Herpesvirus, have been related to CD pathogenesis. Therefore, clinicians need to pay more attention to evaluate CD patients' viral infection history (especially nonresponders to the GFD), to look for effective preventive strategies and educate patients about important risk factors. In addition, there are still viruses whose role in CD pathogenesis has not been fully studied. In this review, current information on the association between CD and various viral infections was gathered to improve knowledge in this subject area and draw researchers'/clinicians' attention to unstudied/less studied viruses in CD pathogenesis, which might guide future prevention approaches.
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Affiliation(s)
- Nastaran Asri
- Celiac Disease and Gluten Related Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahnaz Mohammadi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahtab Jahdkaran
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Rostami-Nejad
- Celiac Disease and Gluten Related Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Mostafa Rezaei-Tavirani
- Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Reza Mohebbi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Scarmozzino R, Zanoni G, Arcolaci A, Ciccocioppo R. Vaccine Efficacy and Safety in Patients with Celiac Disease. Vaccines (Basel) 2024; 12:1328. [PMID: 39771990 PMCID: PMC11679483 DOI: 10.3390/vaccines12121328] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Revised: 10/18/2024] [Accepted: 10/29/2024] [Indexed: 01/04/2025] Open
Abstract
Celiac disease (CD) is an autoimmune disorder caused by gluten intake in genetically predisposed individuals. This article provides an overview of the available data on the risks of infectious diseases and the mechanisms involved in CD, including a detailed analysis of vaccine efficacy, immunogenicity, and safety. The published articles were retrieved from the PubMed database using the terms "celiac disease", "efficacy", "hyposplenism", "immune response", "infections", "immunization", "immunogenicity", "safety", "vaccination", and "vaccine". CD can be associated with several autoimmune diseases, including selective immunoglobulin A deficiency (SIgAD), altered mucosal permeability, and hyposplenism. These conditions entail an increased risk of infections, which can be prevented by targeted vaccinations, although specific recommendations on immunization practices for subjects with CD have not been released. Regarding vaccinations, the immune response to the Hepatitis B virus (HBV) vaccine can be impaired in patients with CD; therefore, proposed strategies to elicit and maintain protective specific antibody titers are summarized. For patients with conditions that put them at risk of infections, vaccinations against Pneumococcus and other encapsulated bacteria should be recommended. Based on the available evidence, the Rotavirus vaccine offered to children could be useful in preventing CD in at-risk subjects. Overall, except for the HBV vaccine, vaccine efficacy in patients with CD is comparable to that in the general population, and no safety concerns have arisen.
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Affiliation(s)
- Rocco Scarmozzino
- Immunology Unit, Azienda Ospedaliera Universitaria Integrata Policlinico G.B. Rossi & University of Verona, 37134 Verona, Italy;
| | - Giovanna Zanoni
- Immunology Unit, Azienda Ospedaliera Universitaria Integrata Policlinico G.B. Rossi & University of Verona, 37134 Verona, Italy;
| | - Alessandra Arcolaci
- Immunology Unit, Azienda Ospedaliera Universitaria Integrata Policlinico G.B. Rossi & University of Verona, 37134 Verona, Italy;
| | - Rachele Ciccocioppo
- Gastroenterology Unit, Department of Medicine, Azienda Ospedaliera Universitaria Integrata Policlinico G.B. Rossi & University of Verona, 37134 Verona, Italy;
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Narciso-Schiavon JL, Schiavon LDL. Hepatitis B and Celiac Disease: a cause for concern? REVISTA COLOMBIANA DE GASTROENTEROLOGÍA 2023; 38:479-485. [DOI: 10.22516/25007440.1016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/11/2025]
Abstract
Some theories suggest that the development of the immune response to clear hepatitis B triggers the intestinal tissue damage seen in celiac disease in genetically predisposed individuals. Although the role of hepatitis B virus infection in the development of autoimmune diseases has been widely discussed in the literature, it remains a controversial topic. Our objective is to review whether there is an association between hepatitis B and celiac disease and the particularities of vaccination against hepatitis B in celiac patients.
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Ulrich JA, Habash NW, Ismail YA, Tremaine WJ, Weaver AL, Murray JA, Loftus EV, Absah I. Effectiveness of Hepatitis B Vaccination for Patients With Inflammatory Bowel and Celiac Disease. Clin Gastroenterol Hepatol 2023; 21:2901-2907.e2. [PMID: 37004970 PMCID: PMC10523860 DOI: 10.1016/j.cgh.2023.03.025] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 03/08/2023] [Accepted: 03/20/2023] [Indexed: 04/04/2023]
Abstract
BACKGROUND & AIMS Guidelines recommend measuring antibody (Ab) titers to hepatitis B virus (HBV) after vaccination for patients with inflammatory bowel disease (IBD) or celiac disease (CD) ("patients with IBD/CD") and revaccinating when titers are low. Few data, however, support this recommendation. We aimed to compare effectiveness of HBV vaccination (immunity and infection rates) for patients with IBD/CD vs matched referents. METHODS Using the Rochester Epidemiology Project, we performed a retrospective cohort study of patients first diagnosed with IBD/CD (index date) while residing in Olmsted County, Minnesota, from January 1, 2000, through December 31, 2019. HBV screening results were obtained from health records. RESULTS In 1264 incident cases of IBD/CD, only 6 HBV infections were diagnosed before the index date. A total of 351 IBD/CD cases had documented receipt of 2 or more HBV vaccines before their index date and had hepatitis B surface antigen Ab (anti-HBs) titers measured after their index date. The proportion of patients with HBV-protective titers (≥10 mIU/mL) decreased with time before plateauing, with protective titer rates of 45% at 5 up to 10 years and 41% at 15 up to 20 years after the last HBV vaccination. The proportion of referents with protective titers also decreased with time and was consistently higher than the levels of patients with IBD/CD within 15 years after the last HBV vaccination. However, no new HBV infection developed in any of 1258 patients with IBD/CD during a median follow-up of 9.4 years (interquartile range, 5.0-14.1 years). CONCLUSIONS Routine testing of anti-HBs titers may not be indicated for fully vaccinated patients with IBD/CD. Additional studies are needed to confirm these findings in other settings and populations.
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Affiliation(s)
- Jessica A Ulrich
- Division of Pediatric Gastroenterology and Hepatology, Mayo Clinic School of Graduate Medical Education, Mayo Clinic College of Medicine and Science, Rochester, Minnesota
| | - Nawras W Habash
- Division of Pediatric Gastroenterology and Hepatology, Mayo Clinic School of Graduate Medical Education, Mayo Clinic College of Medicine and Science, Rochester, Minnesota
| | - Yasmine A Ismail
- Division of Pediatric Gastroenterology and Hepatology, Mayo Clinic School of Graduate Medical Education, Mayo Clinic College of Medicine and Science, Rochester, Minnesota
| | - William J Tremaine
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Amy L Weaver
- Division of Clinical Trials and Biostatistics, Mayo Clinic, Rochester, Minnesota
| | - Joseph A Murray
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Imad Absah
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota; Division of Pediatric Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota.
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ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease. J Pediatr Gastroenterol Nutr 2022; 75:369-386. [PMID: 35758521 DOI: 10.1097/mpg.0000000000003540] [Citation(s) in RCA: 75] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To gather the current evidence and to offer recommendations for follow-up and management. METHODS The Special Interest Group on Celiac Diseases of the European Society of Paediatric Gastroenterology Hepatology and Nutrition formulated ten questions considered to be essential for follow-up care. A literature search (January 2010-March 2020) was performed in PubMed or Medline. Relevant publications were identified and potentially eligible studies were assessed. Statements and recommendations were developed and discussed by all coauthors. Recommendations were voted upon: joint agreement was set as at least 85%. RESULTS Publications (n = 2775) were identified and 164 were included. Using evidence or expert opinion, 37 recommendations were formulated on: The need to perform follow-up, its frequency and what should be assessed, how to assess adherence to the gluten-free diet, when to expect catch-up growth, how to treat anemia, how to approach persistent high serum levels of antibodies against tissue-transglutaminase, the indication to perform biopsies, assessment of quality of life, management of children with unclear diagnosis for which a gluten-challenge is indicated, children with associated type 1 diabetes or IgA deficiency, cases of potential celiac disease, which professionals should perform follow-up, how to improve the communication to patients and their parents/caregivers and transition from pediatric to adult health care. CONCLUSIONS We offer recommendations to improve follow-up of children and adolescents with celiac disease and highlight gaps that should be investigated to further improve management.
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Catassi C, Verdu EF, Bai JC, Lionetti E. Coeliac disease. Lancet 2022; 399:2413-2426. [PMID: 35691302 DOI: 10.1016/s0140-6736(22)00794-2] [Citation(s) in RCA: 212] [Impact Index Per Article: 70.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 04/05/2022] [Accepted: 04/13/2022] [Indexed: 12/14/2022]
Abstract
Coeliac disease is an autoimmune disorder that primarily affects the small intestine, and is caused by the ingestion of gluten in genetically susceptible individuals. Prevalence in the general population ranges from 0·5% to 2%, with an average of about 1%. The development of the coeliac enteropathy depends on a complex immune response to gluten proteins, including both adaptive and innate mechanisms. Clinical presentation of coeliac disease is highly variable and includes classical and non-classical gastrointestinal symptoms, extraintestinal manifestations, and subclinical cases. The disease is associated with a risk of complications, such as osteoporosis and intestinal lymphoma. Diagnosis of coeliac disease requires a positive serology (IgA anti-transglutaminase 2 and anti-endomysial antibodies) and villous atrophy on small-intestinal biopsy. Treatment involves a gluten-free diet; however, owing to the high psychosocial burden of such a diet, research into alternative pharmacological treatments is currently very active.
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Affiliation(s)
- Carlo Catassi
- Department of Specialized Clinical Sciences and Odontostomatology, Polytechnic University of Marche, Ancona, Italy; Celiac Center and Mucosal Immunology and Biology Research, MassGeneral Hospital for Children-Harvard Medical School, Boston, MA, USA.
| | - Elena F Verdu
- Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Julio Cesar Bai
- Department of Medicine, Dr C Bonorino Udaondo Gastroenterology Hospital, Buenos Aires, Argentina; Research Institutes, Universidad del Salvador, Buenos Aires, Argentina
| | - Elena Lionetti
- Department of Specialized Clinical Sciences and Odontostomatology, Polytechnic University of Marche, Ancona, Italy
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Abstract
OBJECTIVE The aim of our study was to assess the response to hepatitis B virus (HBV) vaccination and the risk of HBV infection in patients with celiac disease (CD). PATIENTS AND METHODS We performed a cross-sectional study using the National Health and Nutrition Examination Survey (NHANES) database (2009-2014) to assess the rate of HBV vaccination, immune response, and HBV infection risk in patients with and without CD. We also determined the rate of HBV infection via retrospective analysis of two cohorts: patients seen at Mayo Clinic (1998-2021), and a stable longitudinally observed cohort, the Rochester Epidemiology Project (REP; 2010-2020). RESULTS Based on the NHANES data, the rate of HBV infection in the United States was 0.33% (95% confidence interval 0.25-0.41). Of 93 patients with CD, 46 (49%) were vaccinated for HBV and of the remaining 19,422 without CD, 10,228 (53%) were vaccinated. Twenty-two (48%) vaccinated patients with CD had HBV immunity and 4405 (43.07%) vaccinated patients without CD had HBV immunity, which was not statistically different. In NHANES data, there were no cases of HBV infection in patients with CD. During the study period, 3568 patients with CD were seen at Mayo Clinic and 3918 patients with CD were identified using the REP database. Of those patients with CD, only four (0.11%) at Mayo Clinic and nine (0.23%) of the REP patients had HBV infection. CONCLUSION The rate of HBV vaccination and immunity was similar in individuals with and without CD. Predictably, no increased risk of HBV infection was detected in CD patients. These results do not support screening and revaccination practice for HBV immunity in patients with CD within the United States.
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Aneja A, Lal SB, Sharma AK, Rawat A, Singh S. Clinical Characteristics of Children With Celiac Disease Not Responding to Hepatitis B Vaccination in India. JPGN REPORTS 2021; 2:e046. [PMID: 37206938 PMCID: PMC10191543 DOI: 10.1097/pg9.0000000000000046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 12/15/2020] [Indexed: 05/21/2023]
Abstract
The immunological response to hepatitis B virus (HBV) vaccine may be suboptimal in children with celiac disease (CD), but the reasons for this are not well defined. Objectives This study was undertaken to assess the immune response to HBV vaccine in CD children and to explore the possible factors affecting the immune response. Methods The study population consisted of 3 groups-50 newly diagnosed CD children (group 1), 50 previously diagnosed CD children who were on gluten free diet (GFD) >3 months (group 2), and 100 age and gender matched healthy controls (group 3). The patient characteristics were recorded, and the blood samples were analyzed for HBsAg and anti-HBs titers. The nonresponders were given a booster dose of HBV vaccine and reevaluated after 6 weeks. Results Positive anti-HBs response was found in 46% in newly diagnosed CD children, 60% in CD children on GFD, and 83% in healthy controls (P < 0.001). The immune response to HBV vaccine in CD children was inferior to that in healthy children (53% vs 83%, P < 0.001). The immune response was found to be significantly affected by age at diagnosis, delay in diagnosis, type of presentation, and compliance to GFD. 44 out of 45 (97.77%) nonresponders from CD group seroconverted after a single booster dose. Conclusion Early diagnosis and good compliance to GFD may improve the immune response to HBV vaccine in CD children. Single additional booster dose is sufficient to attain optimal immune response.
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Affiliation(s)
- Aradhana Aneja
- From the Division of Paediatric Gastroenterology, Hepatology & Nutrition
| | - Sadhna B. Lal
- From the Division of Paediatric Gastroenterology, Hepatology & Nutrition
| | | | - Amit Rawat
- Division of Paediatric Immunology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
| | - Surjit Singh
- Division of Paediatric Immunology, Post Graduate Institute of Medical Education & Research, Chandigarh, India
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Association between Elevated TGA-IgA Titers and Older Age at Diagnosis with Absence of HBV Seroconversion in Celiac Children. Vaccines (Basel) 2021; 9:vaccines9020101. [PMID: 33525661 PMCID: PMC7912643 DOI: 10.3390/vaccines9020101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 01/24/2021] [Accepted: 01/25/2021] [Indexed: 11/17/2022] Open
Abstract
Patients with celiac disease can have a low rate of protective hepatitis B (HBV) antibody titers after vaccination. We aimed to evaluate the HBV seroconversion in celiac disease (CD) children at the time of diagnosis as well as to identify the presence of possible predictive factors. Celiac disease children were prospectively enrolled and tested for antibodies against the S protein of HBV (HBsAg) at time of diagnosis between January 2009 and February 2020. Based on the serologic response to the vaccine, “responders” and “non-responders” were identified. Statistical analysis has been performed through R statistical software (3.5.1 version, R core Team) Of 96 CD children evaluated, 41.7% (n = 40) showed non-protective or absent antibody titers against HBV. Elevated IgA-antibodies against transglutaminase 2 (TGA-IgA) values and older age at diagnosis were associated with an absent seroconversion to HBV vaccine, while presenting symptoms were not significant. An elevated prevalence of absent seroconversion to HBV vaccine exists in this cohort of CD patients at the time of disease diagnosis. Elevated TGA-IgA titers and older age at diagnosis seem to negatively predict seroconversion. Further studies are needed to identify the real profile of “non-responders”, aiming to organize surveillance and eventual revaccination strategy.
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Yanny B, Grewal JK, Vaswani VK. Celiac Disease and the Liver. DIAGNOSIS AND MANAGEMENT OF GLUTEN-ASSOCIATED DISORDERS 2021:27-40. [DOI: 10.1007/978-3-030-56722-4_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Passanisi S, Dipasquale V, Romano C. Vaccinations and Immune Response in Celiac Disease. Vaccines (Basel) 2020; 8:278. [PMID: 32517026 PMCID: PMC7349995 DOI: 10.3390/vaccines8020278] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 05/31/2020] [Accepted: 06/02/2020] [Indexed: 12/16/2022] Open
Abstract
Immune response to vaccinations in celiac patients is of growing scientific interest. However, some aspects of the relationship between celiac disease (CD) and vaccines are still unclear. A comprehensive search of published literature using the PubMed database was carried out using the following key terms: "adaptive immunity", "celiac disease", "humoral immune response", "immunization", and "vaccination". To date, there is no evidence showing any causative association between vaccines and CD development. Therefore, vaccinations may be administered according to the modalities and timing of the National Immunization Schedule for each country. The rotavirus vaccine is currently recommended for the general population, and according to some data, it appears to reduce the risk for the development of CD autoimmunity in the early years of life. Regarding the hepatitis B virus, a booster dose of the vaccine is often required due to the low or the lost immune response rate in CD. Furthermore, determination of hepatitis B antibody titers could be useful in newly diagnosed CD subjects regardless of age at diagnosis. Finally, pneumococcal vaccines may be administered in patients with advancing age at diagnosis and concomitant risk factors. Future clinical practice guidelines for vaccination and monitoring programs in celiac patients could be recommended.
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Affiliation(s)
| | | | - Claudio Romano
- Paediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, University of Messina, 98124 Messina, Italy; (S.P.); (V.D.)
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Hayden CA, Landrock D, Hung CY, Ostroff G, Fake GM, Walker JH, Kier A, Howard JA. Co-Administration of Injected and Oral Vaccine Candidates Elicits Improved Immune Responses over Either Route Alone. Vaccines (Basel) 2020; 8:E37. [PMID: 31973150 PMCID: PMC7157212 DOI: 10.3390/vaccines8010037] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 01/15/2020] [Accepted: 01/16/2020] [Indexed: 12/22/2022] Open
Abstract
Infectious diseases continue to be a significant cause of morbidity and mortality, and although efficacious vaccines are available for many diseases, some parenteral vaccines elicit little or no mucosal antibodies which can be a significant problem since mucosal tissue is the point of entry for 90% of pathogens. In order to provide protection for both serum and mucosal areas, we have tested a combinatorial approach of both parenteral and oral administration of antigens for diseases caused by a viral pathogen, Hepatitis B, and a fungal pathogen, Coccidioides. We demonstrate that co-administration by the parenteral and oral routes is a useful tool to increase the overall immune response. This can include achieving an immune response in tissues that are not elicited when using only one route of administration, providing a higher level of response that can lead to fewer required doses or possibly providing a better response for individuals that are considered poor or non-responders.
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Affiliation(s)
- Celine A. Hayden
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, USA; (C.A.H.); (G.M.F.)
| | - Danilo Landrock
- Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A & M University, College Station, TX 77843, USA; (D.L.); (A.K.)
| | - Chiung Yu Hung
- Department of Biology, University of Texas San Antonio, One UTSA Circle, San Antonio, TX 78249, USA;
| | - Gary Ostroff
- Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation St. Biotech 2, Suite 113, Worcester, MA 01605, USA;
| | - Gina M. Fake
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, USA; (C.A.H.); (G.M.F.)
| | - John H. Walker
- Department of Statistics, California Polytechnic State University, San Luis Obispo, CA 93407, USA;
| | - Ann Kier
- Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A & M University, College Station, TX 77843, USA; (D.L.); (A.K.)
| | - John A. Howard
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, USA; (C.A.H.); (G.M.F.)
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Sparks B, Salman S, Shull M, Trout A, Kiel A, Hill I, Ediger T, Boyle B. A Celiac Care Index Improves Care of Pediatric Patients Newly Diagnosed with Celiac Disease. J Pediatr 2020; 216:32-36.e2. [PMID: 31706635 DOI: 10.1016/j.jpeds.2019.09.071] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Revised: 09/12/2019] [Accepted: 09/25/2019] [Indexed: 10/25/2022]
Abstract
OBJECTIVES To describe quality improvement efforts to reduce variability in the care of children diagnosed with celiac disease through use of an institutional patient registry and a chronic care index. STUDY DESIGN An institutional patient registry tracked rates of follow-up visits and repeat serologic testing. A Celiac Care Index that included anthropometrics, biopsy expectations, dietician consultation, and baseline laboratory evaluation was developed to standardize evaluation at diagnosis. Provider education sessions communicated expectations for this standard of care and order sets within the electronic medical record simplified test collection. Data was recorded and reviewed weekly and structured communications with providers were provided biweekly. RESULTS Adherence with follow-up expectations (77%-89% P = .03) and repeat serologic testing (50%-90% P < .0001) significantly increased during the study period. Adherence with completion of the Celiac Care Index resulted in significant improvement in obtaining complete blood count (80%-98% P < .0001), iron (25%-78% P < .0001), ferritin (34%-80% P < .0001), alanine aminotransferase/aspartate aminotransferase (74%-96% P < .0001), thyroid-stimulating hormone (64%-90% P < .0001), vitamin D (36%-83% P < .0001), and hepatitis B immune status (30%-80% P < .0001). Iron deficiency demonstrated by low ferritin levels was common (41%) and a high rate of nonimmunity to hepatitis B (70%) was detected. CONCLUSIONS The Celiac Care Index improved adherence with published care recommendations and reduced variability in baseline evaluation at diagnosis. Laboratory test results indicate further studies are needed to evaluate these recommendations.
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Affiliation(s)
- Brandon Sparks
- Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Riley Hospital for Children at IU Health, Indianapolis, IN.
| | - Salman Salman
- Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Nationwide Children's Hospital, Columbus, OH
| | - Mary Shull
- Digestive Health Institute, Children's Hospital Colorado, Denver, CO
| | - Anne Trout
- Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Nationwide Children's Hospital, Columbus, OH
| | - Ashley Kiel
- Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Nationwide Children's Hospital, Columbus, OH
| | - Ivor Hill
- Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Nationwide Children's Hospital, Columbus, OH
| | - Tracy Ediger
- Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Nationwide Children's Hospital, Columbus, OH
| | - Brendan Boyle
- Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Nationwide Children's Hospital, Columbus, OH
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15
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Abstract
There is substantial variation between individuals in the immune response to vaccination. In this review, we provide an overview of the plethora of studies that have investigated factors that influence humoral and cellular vaccine responses in humans. These include intrinsic host factors (such as age, sex, genetics, and comorbidities), perinatal factors (such as gestational age, birth weight, feeding method, and maternal factors), and extrinsic factors (such as preexisting immunity, microbiota, infections, and antibiotics). Further, environmental factors (such as geographic location, season, family size, and toxins), behavioral factors (such as smoking, alcohol consumption, exercise, and sleep), and nutritional factors (such as body mass index, micronutrients, and enteropathy) also influence how individuals respond to vaccines. Moreover, vaccine factors (such as vaccine type, product, adjuvant, and dose) and administration factors (schedule, site, route, time of vaccination, and coadministered vaccines and other drugs) are also important. An understanding of all these factors and their impacts in the design of vaccine studies and decisions on vaccination schedules offers ways to improve vaccine immunogenicity and efficacy.
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16
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Manti S, Cuppari C, Parisi GF, Tardino L, Salpietro C, Leonardi S. HMGB1 values and response to HBV vaccine in children with celiac disease. Nutrition 2017; 42:20-22. [PMID: 28870474 DOI: 10.1016/j.nut.2017.05.012] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2017] [Revised: 04/30/2017] [Accepted: 05/15/2017] [Indexed: 12/17/2022]
Abstract
OBJECTIVES In addition to its wide clinical variability, celiac disease (CD) can also cause a lower response to the hepatitis B virus (HBV) than healthy individuals. The aim of this study was to examine high mobility group box 1 (HMGB1) as a new potential marker of an inadequate response to HBV vaccine in children with CD at diagnosis before starting a gluten-free diet. METHODS We recruited 49 children with CD who were tested at admission for immunization against HBV. Serum HMGB1 levels were measured by an enzyme-linked immunosorbent assay test. RESULTS Serum HMGB1 levels were significantly higher in nonresponders than in responders (P < 0.05). In the responders group in particular, with reference to the titer of vaccine response, we found a significantly higher serum HMGB1 level in the low responders (P < 0.001). We detected statistically significant higher values of HMGB1 in the typical form of disease presentation than in the atypical or silent form (P < 0.05). In the typical form, we showed even significantly higher HMGB1 values in low responders than in high responders (P < 0.001). With regard to the HLA haplotype and serum HMGB1 levels, any statistically significant difference was detected (P > 0.05). CONCLUSIONS In patients with CD, HMGB1 could represent a new marker that is able to reflect the immune impairment that results in failure of the HBV vaccination.
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Affiliation(s)
- Sara Manti
- Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy
| | - Caterina Cuppari
- Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy
| | - Giuseppe F Parisi
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Lucia Tardino
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Carmelo Salpietro
- Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy
| | - Salvatore Leonardi
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
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17
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Anania C, Olivero F, Spagnolo A, Chiesa C, Pacifico L. Immune response to vaccines in children with celiac disease. World J Gastroenterol 2017; 23:3205-3213. [PMID: 28566880 PMCID: PMC5434426 DOI: 10.3748/wjg.v23.i18.3205] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Revised: 03/07/2017] [Accepted: 04/12/2017] [Indexed: 02/07/2023] Open
Abstract
Celiac disease (CD) is an immune-mediated systemic condition evoked by ingestion of gluten and related prolamines in genetically susceptible subjects. The disease is featured by a variable combination of clinical signs, specific antibodies, HLA-DQ2 and HLA-DQ8 haplotypes, and enteropathy. Vaccination is the most potent intervention for infectious disease prevention. Several factors including age, gender, ethnicity, quality and quantity of vaccine antigen, doses, and route of administration can influence immune response to vaccination, although the main cause of variation in the responsiveness among vaccine recipients is host genetic variability. The HLA system has a fundamental role in identifying the antigens introduced into the host with the vaccines and in the development of specific antibodies, and some HLA phenotypes have been associated with a less effective immunological response. The available literature indicates that the immunological response to vaccines in CD children does not differ markedly from that of general population and antibody titres are high enough to provide long-term protection, except for hepatitis B virus vaccine. In this article, we review and discuss the scarce literature in this field in order to provide clinical practice guidelines to achieve the most efficient monitoring of the response to vaccines in pediatric CD patients.
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18
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Abstract
AIM To evaluate hepatitis B virus (HBV) vaccine response and correlation with human leukocyte antigens (HLA) and/or gluten intake in celiac patients at diagnosis. METHODS Fifty-one patients affected by celiac disease, diagnosed at the Department of Pediatrics of the University of Catania (Italy), were recruited. All patients were tested at admission for immunization against HBV, according to findings from analysis of quantitative HBV surface antibody (anti-HBs). The anti-HBs titer was measured by enzyme-linked immunosorbent assay. Following the international standards, subjects with antibody titer < 10 IU/L were defined as non-responders. The prevalence of responders and non-responders among celiac subjects and the distribution of immunization for age were examined. In addition, the prevalence of responders and non-responders was assessed for correlation to HLA and clinical features at diagnosis of celiac disease. RESULTS The entire study population was divided into three groups according to age: 24 patients aged between 0 to 5.5 years (48.9%, group A); 16 aged between 5.5 and 9.5 years (30.61%, group B); 9 aged between 9.5 and 17 years (18.75%, group C). Comparison of the percentage of responders and non-responders between the youngest and the oldest age group showed no significant difference between the two groups (P > 0.05). With regard to the HLA haplotype, comparison of the distribution of vaccination response showed no statistically significant difference between the different genotypes (homozygosity for the HLADQ2 haplotype compared with HLADQ2/DQ8 heterozygosity or other haplotypes; P > 0.05). Moreover, distribution of the responders according to clinical features of celiac disease showed no statistically significant differences (P > 0.05). CONCLUSION This prospective study confirmed the lower percentage of response to HBV vaccine in celiac subjects. However, the underlying mechanism remains unclear and further studies are needed.
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19
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Filippelli M, Garozzo MT, Capizzi A, Spina M, Manti S, Tardino L, Salpietro C, Leonardi S. Immune response to hepatitis B virus vaccine in celiac subjects at diagnosis. World J Hepatol 2016; 8:1105-1109. [PMID: 27660678 PMCID: PMC5026993 DOI: 10.4254/wjh.v8.i26.1105] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Revised: 07/14/2016] [Accepted: 07/29/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate hepatitis B virus (HBV) vaccine response and correlation with human leukocyte antigens (HLA) and/or gluten intake in celiac patients at diagnosis. METHODS Fifty-one patients affected by celiac disease, diagnosed at the Department of Pediatrics of the University of Catania (Italy), were recruited. All patients were tested at admission for immunization against HBV, according to findings from analysis of quantitative HBV surface antibody (anti-HBs). The anti-HBs titer was measured by enzyme-linked immunosorbent assay. Following the international standards, subjects with antibody titer < 10 IU/L were defined as non-responders. The prevalence of responders and non-responders among celiac subjects and the distribution of immunization for age were examined. In addition, the prevalence of responders and non-responders was assessed for correlation to HLA and clinical features at diagnosis of celiac disease. RESULTS The entire study population was divided into three groups according to age: 24 patients aged between 0 to 5.5 years (48.9%, group A); 16 aged between 5.5 and 9.5 years (30.61%, group B); 9 aged between 9.5 and 17 years (18.75%, group C). Comparison of the percentage of responders and non-responders between the youngest and the oldest age group showed no significant difference between the two groups (P > 0.05). With regard to the HLA haplotype, comparison of the distribution of vaccination response showed no statistically significant difference between the different genotypes (homozygosity for the HLADQ2 haplotype compared with HLADQ2/DQ8 heterozygosity or other haplotypes; P > 0.05). Moreover, distribution of the responders according to clinical features of celiac disease showed no statistically significant differences (P > 0.05). CONCLUSION This prospective study confirmed the lower percentage of response to HBV vaccine in celiac subjects. However, the underlying mechanism remains unclear and further studies are needed.
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Affiliation(s)
- Martina Filippelli
- Martina Filippelli, Maria Teresa Garozzo, Antonino Capizzi, Massimo Spina, Lucia Tardino, Salvatore Leonardi, Department of Medical and Pediatric Sciences, University of Catania, 95100 Catania, Italy
| | - Maria Teresa Garozzo
- Martina Filippelli, Maria Teresa Garozzo, Antonino Capizzi, Massimo Spina, Lucia Tardino, Salvatore Leonardi, Department of Medical and Pediatric Sciences, University of Catania, 95100 Catania, Italy
| | - Antonino Capizzi
- Martina Filippelli, Maria Teresa Garozzo, Antonino Capizzi, Massimo Spina, Lucia Tardino, Salvatore Leonardi, Department of Medical and Pediatric Sciences, University of Catania, 95100 Catania, Italy
| | - Massimo Spina
- Martina Filippelli, Maria Teresa Garozzo, Antonino Capizzi, Massimo Spina, Lucia Tardino, Salvatore Leonardi, Department of Medical and Pediatric Sciences, University of Catania, 95100 Catania, Italy
| | - Sara Manti
- Martina Filippelli, Maria Teresa Garozzo, Antonino Capizzi, Massimo Spina, Lucia Tardino, Salvatore Leonardi, Department of Medical and Pediatric Sciences, University of Catania, 95100 Catania, Italy
| | - Lucia Tardino
- Martina Filippelli, Maria Teresa Garozzo, Antonino Capizzi, Massimo Spina, Lucia Tardino, Salvatore Leonardi, Department of Medical and Pediatric Sciences, University of Catania, 95100 Catania, Italy
| | - Carmelo Salpietro
- Martina Filippelli, Maria Teresa Garozzo, Antonino Capizzi, Massimo Spina, Lucia Tardino, Salvatore Leonardi, Department of Medical and Pediatric Sciences, University of Catania, 95100 Catania, Italy
| | - Salvatore Leonardi
- Martina Filippelli, Maria Teresa Garozzo, Antonino Capizzi, Massimo Spina, Lucia Tardino, Salvatore Leonardi, Department of Medical and Pediatric Sciences, University of Catania, 95100 Catania, Italy
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20
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Snyder J, Butzner JD, DeFelice AR, Fasano A, Guandalini S, Liu E, Newton KP. Evidence-Informed Expert Recommendations for the Management of Celiac Disease in Children. Pediatrics 2016; 138:peds.2015-3147. [PMID: 27565547 DOI: 10.1542/peds.2015-3147] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/23/2016] [Indexed: 12/11/2022] Open
Abstract
Although the need for effective long-term follow-up for patients with celiac disease (CD) has been recognized by many expert groups, published practice guidelines have not provided a clear approach for the optimal management of these patients. In an attempt to provide a thoughtful and practical approach for managing these patients, a group of experts in pediatric CD performed a critical review of the available literature in 6 categories associated with CD to develop a set of best practices by using evidence-based data and expert opinion. The 6 categories included the following: bone health, hematologic issues, endocrine problems, liver disease, nutritional issues, and testing. Evidence was assessed by using standardized criteria for evaluating the quality of the data, grade of evidence, and strength of conclusions. Over 600 publications were reviewed, and 172 were chosen for inclusion. The thorough review of the results demonstrated that the quality of the data available was often insufficient to provide unequivocal best practices. However, using the available data and the clinical experience of the panel, a practical framework for the management of children with CD was created. These recommendations were developed by our expert panel and do not necessarily reflect the policy of the American Academy of Pediatrics. The potential usefulness of these best practices is underscored by the fact that consensus, measured by the outcome of anonymous voting, was reached by the panel for 24 of the 25 questions. We hope that these best practices may be useful to the pediatric gastroenterology and larger general pediatric communities.
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Affiliation(s)
- John Snyder
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Children's National Health Systems, Washington, District of Columbia;
| | - J Decker Butzner
- Division of Paediatric Gastroenterology, Hepatology and Nutrition, University of Calgary, Calgary, Alberta, Canada
| | - Amy R DeFelice
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, New York-Presbyterian Hospital, Columbia University, New York, New York
| | - Alessio Fasano
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Massachusetts General Hospital for Children, Boston, Massachusetts
| | - Stefano Guandalini
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Chicago Medical Center, Chicago, Illinois
| | - Edwin Liu
- Digestive Health Institute, Children's Hospital Colorado, Aurora, Colorado; and
| | - Kimberly P Newton
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, Rady Children's Hospital and University of California San Diego School of Medicine, San Diego, California
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21
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Onal Z, Ersen A, Bayramoglu E, Yaroglu Kazancı S, Onal H, Adal E. Seroprotection status of hepatitis B and measles vaccines in children with type 1 diabetes mellitus. J Pediatr Endocrinol Metab 2016; 29:1013-7. [PMID: 27658137 DOI: 10.1515/jpem-2015-0211] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2016] [Accepted: 07/18/2016] [Indexed: 01/05/2023]
Abstract
BACKGROUND Type 1 diabetes mellitus (T1DM) is speculated to have an impaired immunological response to vaccines. This paper aimed to investigate the presence of specific antibodies against hepatitis B virus (HBV) and measles in diabetic children who had been immunized according to the standard national calendar of immunization. METHODS Two hundred and one diabetic children and 140 healthy controls were prospectively evaluated. Antibodies against hepatitis B (anti-HBs) and measles were detected in all individuals who completed the vaccination schedule. We noted onset of T1DM, duration of the disease, diabetes-related autoantibodies and mean HbA1c levels. RESULTS Some 72.6% of diabetics and 82.1% of controls had anti-HBs (+) (p=0.04). We found a reduced efficacy of measles vaccination in anti-HBs (-) diabetic children (p=0.009), even though there was no significant difference between the study and control groups. Onset of the disease was earlier in anti-HBs (-) diabetics than in controls (p=0.038). No difference with respect to other parameters was found. CONCLUSIONS Our data showed a reduced seroprotection rate for HBV vaccination in diabetic children and for measles with anti-HBs (-) diabetics. Larger studies should be encouraged to confirm the vaccine efficacy in diabetic children and to elucidate possible pathogenic mechanisms.
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22
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Marciano F, Savoia M, Vajro P. Celiac disease-related hepatic injury: Insights into associated conditions and underlying pathomechanisms. Dig Liver Dis 2016; 48:112-119. [PMID: 26711682 DOI: 10.1016/j.dld.2015.11.013] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/01/2015] [Revised: 11/11/2015] [Accepted: 11/17/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Celiac disease (CD) is the most common autoimmune enteropathy. Clinical manifestations may range from a typical malabsorption syndrome to several apparently unrelated extra-intestinal symptoms. AIM Here we specifically focus on the spectrum of CD-related liver disorders and the underlying pathomechanisms. METHODS A computer-based search up to August 2015 was completed using appropriate keywords. References from selected papers were also reviewed and used if relevant. RESULTS An unexplained hypertransaminasemia with nonspecific histologic hepatic changes is the most common hepatic presentation. CD however can coexist with a number of liver disorders such as Autoimmune Hepatitis, Autoimmune Cholangitis, Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis requiring a specific treatment in addition to gluten-free diet. CD has also been associated with Viral Hepatitis, Fatty Liver, Non-Alcoholic Steatohepatitis and some severe cryptogenic hepatopaties in the liver transplantation list. Pathomechanisms underlying hepatic injury in CD are multiple, appear still not completely defined and may probably co-occur. CONCLUSIONS An ever-increasing number of CD-related liver injuries exist, probably representing a continuum of a same disorder where genetic predisposition, timing, and duration of previous gluten exposure might influence the reversibility of liver damage. Evidences, although not conclusive, support therefore testing for CD also in cryptogenic hepatobiliary conditions where the relationship with CD has not yet been fully investigated.
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MESH Headings
- Autoimmune Diseases/epidemiology
- Autoimmune Diseases/immunology
- Celiac Disease/epidemiology
- Celiac Disease/immunology
- Cholangitis/epidemiology
- Cholangitis/immunology
- Cholangitis, Sclerosing/epidemiology
- Cholangitis, Sclerosing/immunology
- Comorbidity
- Hepatitis, Autoimmune/epidemiology
- Hepatitis, Autoimmune/immunology
- Hepatitis, Viral, Human/epidemiology
- Hepatitis, Viral, Human/immunology
- Humans
- Liver Cirrhosis, Biliary/epidemiology
- Liver Cirrhosis, Biliary/immunology
- Liver Diseases/enzymology
- Liver Diseases/epidemiology
- Liver Diseases/immunology
- Non-alcoholic Fatty Liver Disease/epidemiology
- Non-alcoholic Fatty Liver Disease/immunology
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Affiliation(s)
- Francesca Marciano
- Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Naples, Italy.
| | - Marcella Savoia
- Department of Molecular Medicine and Medical Biotechnology, University of Naples "Federico II", Naples, Italy.
| | - Pietro Vajro
- Department of Medicine and Surgery, Pediatrics Section, University of Salerno, Baronissi, Italy; ELFID, University of Naples "Federico II", Naples, Italy.
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23
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Leonardi S, Filippelli M, Manti S, Cuppari C, Salpietro C. Extending the Debate on Poor Response to Hepatitis B Virus Vaccination in Children With Celiac Disease: Which Question Remains? HEPATITIS MONTHLY 2015; 15:e30888. [PMID: 26587037 PMCID: PMC4644565 DOI: 10.5812/hepatmon.30888] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/19/2015] [Accepted: 07/29/2015] [Indexed: 12/11/2022]
Affiliation(s)
- Salvatore Leonardi
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Martina Filippelli
- Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
| | - Sara Manti
- Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy
| | - Caterina Cuppari
- Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy
| | - Carmelo Salpietro
- Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy
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24
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Opri R, Veneri D, Mengoli C, Zanoni G. Immune response to Hepatitis B vaccine in patients with celiac disease: A systematic review and meta-analysis. Hum Vaccin Immunother 2015; 11:2800-5. [PMID: 26378476 DOI: 10.1080/21645515.2015.1069448] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
It is debated whether patients with celiac disease (CD) have non-protective antibody responses to HBV vaccination more frequently than non-affected subjects. To perform a literature review and meta-analysis on protective response to HBV vaccination in CD patients. RCTs and observational controlled studies were eligible. Outcome of interest was an anti-HBs (HBsAb) titer ≥ 10 IU/L after last vaccine dose. Comparative index was rate ratio (RR). Heterogeneity between studies was addressed and funnel plots were analyzed. Meta-regression models were applied to investigate effect size due to study-specific variables. Twelve retrospective studies on a total of 1,447 participants and 4 prospective studies on 184 subjects were selected. The RR was 0.732 (95% C.I.: 0.664-0.808) and 0.777 (95% C.I.: 0.629-0.960) in the prospective and retrospective studies, respectively. The I(2), indicating heterogeneity, was 51.1% in retrospective, 39.8% in prospective studies. Non-protective antibody responses occurred more frequently in patients than controls. Due to limitations in the available studies, additional trials to evaluate post-vaccination HBsAb titer in CD patients are needed.
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Affiliation(s)
- R Opri
- a Department of Pathology and Diagnostics ; Section of Immunology; University of Verona ; Verona , Italy
| | - D Veneri
- b Department of Medicine ; Section of Hematology; University of Verona ; Verona , Italy
| | - C Mengoli
- c Infectious Diseases; University of Padua ; Padua , Italy
| | - G Zanoni
- a Department of Pathology and Diagnostics ; Section of Immunology; University of Verona ; Verona , Italy
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25
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Filippelli M, Lionetti E, Pulvirenti A, Gennaro A, Lanzafame A, Marseglia GL, Salpietro C, Rosa ML, Leonardi S. New approaches in hepatitis B vaccination for celiac disease. Immunotherapy 2015; 6:945-52. [PMID: 25313572 DOI: 10.2217/imt.14.64] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Celiac disease (CD) is a gluten-induced immune-mediated disorder that has been associated with a defective response to the hepatitis B virus (HBV) vaccination. This unresponsiveness could lead to a world health problem, because non-responder patients could represent a reservoir of HBV-susceptible people that will persist as healthy carriers, leading to the diffusion of the disease. This article presents a literature review of both intramuscular (IM) and intradermal (ID) routes for boosters in celiac patients. We used PubMed database and generated the odds ratio (OR) of the response on the basis of electronic searches of clinical trials. Although our results confirm the positive response of celiac patients to IM vaccination, the ID route seems to be better than the conventional one, since it could provide a saving in cost and a greater immunogenicity.
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Affiliation(s)
- Martina Filippelli
- Department of Medical & Pediatric Science, University of Catania, Catania, Italy
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26
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Walkiewicz-Jedrzejczak D, Egberg M, Nelson C, Eickoff J. Evaluation of the response to vaccination with hepatitis B vaccine in pediatric patients diagnosed with celiac disease. SAGE Open Med 2014; 2:2050312114563346. [PMID: 26770758 PMCID: PMC4607240 DOI: 10.1177/2050312114563346] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2014] [Accepted: 11/11/2014] [Indexed: 12/28/2022] Open
Abstract
Background: A gap exists in the literature on celiac disease populations and the response to hepatitis B vaccination. Objective: To identify pediatric patients with celiac disease who received the primary hepatitis B vaccination and investigate their response to vaccine. Design/Methods: Patients underwent blood draw for hepatitis B surface antibody titers. Patients with undetectable or non-protective HBsAb titers were contacted. Study outcome measures and patient characteristics variables were summarized by means, standard deviations, medians, and ranges. A two-sample t-test was used to compare normally distributed continuous variables between responders and non-responders. Results: In all, 58% of patients did not meet the threshold for “protective” antibody titers. The mean time between completion of hepatitis B vaccination and diagnosis of celiac disease was 8.1 years for responders versus 10.5 years for non-responders. In a multivariate analysis, time between completion of vaccine and diagnosis of celiac disease was statistically significant predictor of response with an adjusted odds ratio of 0.69 (95% confidence interval: 0.50–0.95; p = 0.021). Conclusion: Our celiac disease population shows a high hepatitis B vaccine failure. The time between completion of vaccine series and diagnosis of celiac disease is an independent predictor for response.
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Affiliation(s)
| | - Matthew Egberg
- Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Catherine Nelson
- Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
| | - Jens Eickoff
- Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
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27
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Filippelli M, Lionetti E, Gennaro A, Lanzafame A, Arrigo T, Salpietro C, La Rosa M, Leonardi S. Hepatitis B vaccine by intradermal route in non responder patients: An update. World J Gastroenterol 2014; 20:10383-10394. [PMID: 25132754 PMCID: PMC4130845 DOI: 10.3748/wjg.v20.i30.10383] [Citation(s) in RCA: 64] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2013] [Revised: 03/12/2014] [Accepted: 04/29/2014] [Indexed: 02/06/2023] Open
Abstract
Vaccination is the main prophylactic measure to reduce the mortality caused by hepatitis B virus (HBV) infection in healthy subjects since the immune response to hepatitis B recombinant vaccination occurs in over 90% of general population. Individuals who develop an anti-HBs titer less than 10 mIU/mL after primary vaccination cycle are defined “no responders”. Many factors could cause a non response to the HBV vaccination, such as administration of the vaccine in buttocks, impaired vaccine storage conditions, drug abuse, smoking, infections and obesity. Moreover there are some diseases, like chronic kidney disease, human immunodeficiency virus infection, chronic liver disease, celiac disease, thalassaemia, type I diabetes mellitus, down’s syndrome and other forms of mental retardation that are characterized by a poorer response to HBV vaccination than healthy subjects. To date it is still unclear how to treat this group of patients at high risk of hepatitis B infection. Recent studies seem to indicate that the administration of HBV recombinant vaccine by the intradermal route is very effective and could represent a more useful strategy than intramuscular route. This review focuses on the use of anti hepatitis B vaccine by intradermal route as alternative to conventional intramuscular vaccine in all non responder patients. A comprehensive review of the literature using PubMed database, with appropriate terms, was undertaken for articles in English published since 1983. The literature search was undertaken in September 2013.
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28
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Hayden CA, Smith EM, Turner DD, Keener TK, Wong JC, Walker JH, Tizard IR, Jimenez-Flores R, Howard JA. Supercritical fluid extraction provides an enhancement to the immune response for orally-delivered hepatitis B surface antigen. Vaccine 2014; 32:1240-6. [PMID: 24486361 DOI: 10.1016/j.vaccine.2014.01.037] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2013] [Revised: 12/27/2013] [Accepted: 01/14/2014] [Indexed: 01/27/2023]
Abstract
The hepatitis B virus continues to be a major pathogen worldwide despite the availability of an effective parenteral vaccine for over 20 years. Orally-delivered subunit vaccines produced in maize may help to alleviate the disease burden by providing a low-cost, heat-stable alternative to the parenteral vaccine. Oral subunit vaccination has been an elusive goal due to the large amounts of antigen required to induce an immunologic response when administered through the digestive tract. Here we show that high levels of HBsAg were obtained in maize grain, the grain was formed into edible wafers, and wafers were fed to mice at a concentration of approximately 300 μg/g. When these wafers were made with supercritical fluid extraction (SFE)-treated maize material, robust IgG and IgA responses in sera were observed that were comparable to the injected commercial vaccine (Recombivax(®)). In addition, all mice administered SFE wafers showed high secretory IgA titers in fecal material whereas Recombivax(®) treated mice showed no detectable titer. Increased salivary IgA titers were also detected in SFE-fed mice but not in Recombivax(®) treated mice. Wafers made from hexane-treated or full fat maize material induced immunologic responses, but fecal titers were attenuated relative to those produced by SFE-treated wafers. These responses demonstrate the feasibility of using a two-dose oral vaccine booster in the absence of an adjuvant to induce immunologic responses in both sera and at mucosal surfaces, and highlight the potential limitations of using an exclusively parenteral dosing regime.
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Affiliation(s)
- Celine A Hayden
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, USA
| | - Emily M Smith
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, USA
| | - Debra D Turner
- Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA
| | - Todd K Keener
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, USA
| | - Jeffrey C Wong
- Horticulture and Crop Science Department, California Polytechnic State University, San Luis Obispo, CA 93407, USA
| | - John H Walker
- Department of Statistics, California Polytechnic State University, San Luis Obispo, CA 93407, USA
| | - Ian R Tizard
- Department of Veterinary Pathobiology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843, USA
| | - Rafael Jimenez-Flores
- Dairy Product Technology Center, California Polytechnic State University, San Luis Obispo, CA 93407, USA
| | - John A Howard
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, USA.
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Sokal EM, Paganelli M, Wirth S, Socha P, Vajro P, Lacaille F, Kelly D, Mieli-Vergani G. Management of chronic hepatitis B in childhood: ESPGHAN clinical practice guidelines: consensus of an expert panel on behalf of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition. J Hepatol 2013; 59:814-29. [PMID: 23707367 DOI: 10.1016/j.jhep.2013.05.016] [Citation(s) in RCA: 139] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2012] [Revised: 05/09/2013] [Accepted: 05/13/2013] [Indexed: 02/06/2023]
Affiliation(s)
- Etienne M Sokal
- Pediatric Gastroenterology & Hepatology, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain and Cliniques Universitaires Saint Luc, Brussels, Belgium.
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Genome-wide characterization of transcriptional patterns in high and low antibody responders to rubella vaccination. PLoS One 2013; 8:e62149. [PMID: 23658707 PMCID: PMC3641062 DOI: 10.1371/journal.pone.0062149] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2012] [Accepted: 03/18/2013] [Indexed: 12/16/2022] Open
Abstract
Immune responses to current rubella vaccines demonstrate significant inter-individual variability. We performed mRNA-Seq profiling on PBMCs from high and low antibody responders to rubella vaccination to delineate transcriptional differences upon viral stimulation. Generalized linear models were used to assess the per gene fold change (FC) for stimulated versus unstimulated samples or the interaction between outcome and stimulation. Model results were evaluated by both FC and p-value. Pathway analysis and self-contained gene set tests were performed for assessment of gene group effects. Of 17,566 detected genes, we identified 1,080 highly significant differentially expressed genes upon viral stimulation (p<1.00E−15, FDR<1.00E−14), including various immune function and inflammation-related genes, genes involved in cell signaling, cell regulation and transcription, and genes with unknown function. Analysis by immune outcome and stimulation status identified 27 genes (p≤0.0006 and FDR≤0.30) that responded differently to viral stimulation in high vs. low antibody responders, including major histocompatibility complex (MHC) class I genes (HLA-A, HLA-B and B2M with p = 0.0001, p = 0.0005 and p = 0.0002, respectively), and two genes related to innate immunity and inflammation (EMR3 and MEFV with p = 1.46E−08 and p = 0.0004, respectively). Pathway and gene set analysis also revealed transcriptional differences in antigen presentation and innate/inflammatory gene sets and pathways between high and low responders. Using mRNA-Seq genome-wide transcriptional profiling, we identified antigen presentation and innate/inflammatory genes that may assist in explaining rubella vaccine-induced immune response variations. Such information may provide new scientific insights into vaccine-induced immunity useful in rational vaccine development and immune response monitoring.
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Zingone F, Capone P, Tortora R, Rispo A, Morisco F, Caporaso N, Imperatore N, De Stefano G, Iovino P, Ciacci C. Role of gluten intake at the time of hepatitis B virus vaccination in the immune response of celiac patients. CLINICAL AND VACCINE IMMUNOLOGY : CVI 2013; 20:660-662. [PMID: 23446217 PMCID: PMC3647759 DOI: 10.1128/cvi.00729-12] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/13/2012] [Accepted: 02/19/2013] [Indexed: 02/07/2023]
Abstract
Some reports have demonstrated an inadequate response to hepatitis B vaccination in patients affected by celiac disease. The aim of our study was to evaluate hepatitis B vaccination response in relation to gluten exposure status in patients with celiac disease. To measure the gluten exposure status at the time of vaccination, we considered three groups: group A (exposed to gluten), including patients vaccinated as 12-year-old adolescents (the celiac disease diagnosis was established after vaccination); group B (not exposed to gluten), including patients vaccinated as 12-year-old adolescents on a gluten-free diet at the time of vaccination; and group C (infants), including patients vaccinated at birth. The response of celiac patients to hepatitis B vaccination was compared to that of healthy subjects, i.e., those in the control group (group D). This study included 163 celiac patients (group A, 57 patients; group B, 46 patients; and group C, 60 patients) and 48 controls (group D). An inadequate response to hepatitis B immunization was present in 43.9% of patients in group A, 34.8% of patients in group B, 58.3% of patients in group C, and 8.3% of patients in group D (group A versus group D, P < 0.001; group B versus group D, P = 0.002; group C versus group D, P = 0.001) (no significant difference for group A versus group B and group A versus group C was evident). Our data suggest that gluten exposure does not influence the response to hepatitis B immunization and that the human leukocyte antigen probably plays the main immunological role in poor responses to hepatitis B-vaccinated celiac patients.
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Affiliation(s)
- F. Zingone
- Department of Medicine and Surgery, University of Salerno, Salerno, Italy
| | - P. Capone
- Department of Clinical and Experimental Medicine, Unit of Gastroenterology, University of Naples Federico II, Naples, Italy
| | - R. Tortora
- Department of Clinical and Experimental Medicine, Unit of Gastroenterology, University of Naples Federico II, Naples, Italy
| | - A. Rispo
- Department of Clinical and Experimental Medicine, Unit of Gastroenterology, University of Naples Federico II, Naples, Italy
| | - F. Morisco
- Department of Clinical and Experimental Medicine, Unit of Gastroenterology, University of Naples Federico II, Naples, Italy
| | - N. Caporaso
- Department of Clinical and Experimental Medicine, Unit of Gastroenterology, University of Naples Federico II, Naples, Italy
| | - N. Imperatore
- Department of Clinical and Experimental Medicine, Unit of Gastroenterology, University of Naples Federico II, Naples, Italy
| | - G. De Stefano
- Department of Clinical and Experimental Medicine, Unit of Gastroenterology, University of Naples Federico II, Naples, Italy
| | - P. Iovino
- Department of Medicine and Surgery, University of Salerno, Salerno, Italy
| | - C. Ciacci
- Department of Medicine and Surgery, University of Salerno, Salerno, Italy
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Vitaliti G, Praticò AD, Cimino C, Di Dio G, Lionetti E, La Rosa M, Leonardi S. Hepatitis B vaccine in celiac disease: Yesterday, today and tomorrow. World J Gastroenterol 2013; 19:838-45. [PMID: 23430309 PMCID: PMC3574880 DOI: 10.3748/wjg.v19.i6.838] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2012] [Revised: 10/12/2012] [Accepted: 10/16/2012] [Indexed: 02/06/2023] Open
Abstract
Some studies showed that in celiac patients the immunological response to vaccination is similar to that one found in general population except for vaccine against hepatitis B virus (HBV). The non-responsiveness to HBV vaccine has also been described in healthy people, nevertheless the number of non-responders has been demonstrated to be higher in celiac disease (CD) patients than in healthy controls. Several hypothesis explaining this higher rate of unresponsiveness to HBV vaccine in CD patients have been described, such as the genetic hypothesis, according with CD patients carrying the disease-specific haplotype HLA-B8, DR3, and DQ2, show a lower response to HBV vaccine both in clinical expressed CD patients and in healthy people carrying the same haplotype. On the other hand, it has been demonstrated that the gluten intake during the vaccination seems to influence the response to the same vaccine. Moreover, it has been demonstrated a possible genetic predisposition to hepatitis B vaccine non-responsiveness likely due to the presence of specific human leukocyte antigen haplotypes and specific single nucleotide polymorphism in genes of cytokine/cytokine receptors and toll like receptors, but the pathogenic mechanism responsible for this low responsiveness still remains unclear. The aim of this review is to focus on the possible pathogenic causes of unresponsiveness to HBV vaccine in CD patients and to propose an alternative vaccination schedule in order to improve the responsiveness to HBV vaccine in this at-risk patients.
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Leonardi S, Praticò AD, Lionetti E, Spina M, Vitaliti G, Rosa ML. Intramuscular vs intradermal route for hepatitis B booster vaccine in celiac children. World J Gastroenterol 2012; 18:5729-33. [PMID: 23155313 PMCID: PMC3484341 DOI: 10.3748/wjg.v18.i40.5729] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2012] [Revised: 07/16/2012] [Accepted: 08/14/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To compare intradermal (ID) and intramuscular (IM) booster doses, which have been used in healthy and high risk subjects, such as healthcare workers, haemodialysis patients, human immunodeficiency virus patients, and renal transplant recipients unresponsive to initial hepatitis B vaccination, in celiac individuals.
METHODS: We conducted our study on 58 celiac patients, vaccinated in the first year of life, whose blood analysis had showed the absence of protective hepatitis B virus (HBV) antibodies. All patients had received the last vaccine injection at least one year before study enrolment and they had been on a gluten free diet for at least 1 year. In all patients we randomly performed an HBV vaccine booster dose by ID or IM route. Thirty celiac patients were revaccinated with recombinant hepatitis B vaccine (Engerix B) 2 μg by the ID route, while 28 celiac patients were revaccinated with Engerix B 10 μg by the IM route. Four weeks after every booster dose, the anti-hepatitis B surface (HBs) antibody titer was measured by an enzyme-linked immune-adsorbent assay. We performed a maximum of three booster doses in patients with no anti-HBs antibodies after the first or the second vaccine dose. The cut off value for a negative anti-HBs antibody titer was 10 IU/L. Patients with values between 10 and 100 IU/L were considered "low responders" while patients with an antibody titer higher than 1000 IU/L were considered "high responders".
RESULTS: No significant difference in age, gender, duration of illness, and years of gluten intake was found between the two groups. We found a high percentage of "responders" after the first booster dose (ID = 76.7%, IM = 78.6%) and a greater increase after the third dose (ID = 90%, IM = 96.4%) of vaccine in both groups. Moreover we found a significantly higher number of high responders (with an anti-HBs antibody titer > 1000 IU/L) in the ID (40%) than in the IM (7.1%) group, and this difference was evident after the first booster dose of vaccination (P < 0.01). No side effects were recorded in performing delivery of the vaccine by either the ID or IM route.
CONCLUSION: Our study suggests that both ID and IM routes are effective and safe options to administer a booster dose of HBV vaccine in celiac patients. However the ID route seems to achieve a greater number of high responders and to have a better cost/benefit ratio.
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Hayden CA, Egelkrout EM, Moscoso AM, Enrique C, Keener TK, Jimenez-Flores R, Wong JC, Howard JA. Production of highly concentrated, heat-stable hepatitis B surface antigen in maize. PLANT BIOTECHNOLOGY JOURNAL 2012; 10:979-84. [PMID: 22816734 PMCID: PMC3517206 DOI: 10.1111/j.1467-7652.2012.00727.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/13/2023]
Abstract
Plant-based oral vaccines are a promising emergent technology that could help alleviate disease burden worldwide by providing a low-cost, heat-stable, oral alternative to parenterally administered commercial vaccines. Here, we describe high-level accumulation of the hepatitis B surface antigen (HBsAg) at a mean concentration of 0.51%TSP in maize T1 seeds using an improved version of the globulin1 promoter. This concentration is more than fourfold higher than any previously reported lines. HBsAg expressed in maize seeds was extremely heat stable, tolerating temperatures up to 55 °C for 1 month without degradation. Optimal heat stability was achieved after oil extraction of ground maize material, either by supercritical fluid extraction or hexane treatment. The contributions of this material towards the development of a practical oral vaccine delivery system are discussed.
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Affiliation(s)
- Celine A. Hayden
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407
| | - Erin M. Egelkrout
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407
| | - Alessa M. Moscoso
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407
| | - Cristina Enrique
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407
| | - Todd K. Keener
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407
| | - Rafael Jimenez-Flores
- Dairy Science Department, California Polytechnic State University, San Luis Obispo, CA 93407
| | - Jeffrey C. Wong
- Horticulture and Crop Science Department, California Polytechnic State University, San Luis Obispo, CA 93407
| | - John A. Howard
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407
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Mannam VKR, Santos M, Lewis RE, Cruse JM. Decreased humoral antibody episodes of acute renal allograft rejection in recipients expressing the HLA-DQβ1*0202 allele. Exp Mol Pathol 2012; 93:190-2. [PMID: 22609240 DOI: 10.1016/j.yexmp.2012.05.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2012] [Revised: 05/03/2012] [Accepted: 05/03/2012] [Indexed: 01/28/2023]
Abstract
The present investigation was designed to show the effect of human leukocyte antigen (HLA) class II molecular allelic specificities in the recipient on the induction of humoral antibody rejection, identified by C4d peritubular capillary staining, as well as specific antibody identified by Luminex technology. Major histocompatibility complex (MHC) class II molecules are expressed on dendritic cells, macrophages, and B lymphocytes and they present antigenic peptides to CD4 positive T lymphocytes. Human renal peritubular and glomerular capillaries express class II MHC molecules upon activation. Expression of class II molecules on renal microvascular endothelial cells exposes them to possible interaction with specific circulating antibodies. We hypothesize that HLA-DQβ1*0202 expression in recipients decreases the likelihood of antibody-mediated renal allograft rejection. We found that 80% (=25) of DQ2 positive haplotype recipients failed to induce humoral antibody renal allograft rejection and 20% (n=25) of DQ2 positive haplotype recipients induced humoral antibody renal allograft rejection (p=0.008). By contrast, 48% (n=46) of DQ2 negative haplotype recipients failed to induce a humoral antibody component of renal allograft rejection and 52% (n=46) of DQ2 negative haplotype recipients induced humoral antibody-mediated renal allograft rejection. Our results suggest that recipients who express the DQβ1*0202 allele are less likely to induce a humoral antibody component of acute renal allograft rejection than are those expressing DQ1, DQ3, or DQ4 alleles. DQβ1*0202 allele expression in recipients could possibly be protective against acute humoral allograft rejection and might serve as a future criterion in recipient selection and in appropriate therapy for acute renal rejection episodes.
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Affiliation(s)
- Venkat K R Mannam
- Department of Pathology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
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Fagundes GD, Tabalipa FDO, Silva JD. Antibody levels in children after 10 years of vaccination against hepatitis B: a brazilian community-based study. Rev Soc Bras Med Trop 2012; 45:260-2. [DOI: 10.1590/s0037-86822012000200024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2010] [Accepted: 07/28/2011] [Indexed: 01/05/2023] Open
Abstract
INTRODUCTION: It is known that the hepatitis B (HB) vaccine is effective, but it is alarming that sudden drops of antibody levels may coincide with the onset of adolescence. METHODS: Antibody levels against HB vaccine surface antigen (anti-HBs) and HB vaccine core antigen (anti-HBc) were measured on the blood samples of children with a mean age of 11.4 years. RESULTS: About 54.8% had protective levels of anti-HBs. Of those who were anti-HBc-positive (4.4%), an average of 218.4 anti-HBs mIU/mL was found. CONCLUSIONS: Immunological protection was found in the majority of children. However, more studies are needed to elucidate the heritability of nonresponders and establish strategies against such events.
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Affiliation(s)
| | | | - Jane da Silva
- Universidade do Sul de Santa Catarina; Universidade do Sul de Santa Catarina
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Hayden CA, Streatfield SJ, Lamphear BJ, Fake GM, Keener TK, Walker JH, Clements JD, Turner DD, Tizard IR, Howard JA. Bioencapsulation of the hepatitis B surface antigen and its use as an effective oral immunogen. Vaccine 2012; 30:2937-42. [PMID: 22406456 DOI: 10.1016/j.vaccine.2012.02.072] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2011] [Revised: 02/05/2012] [Accepted: 02/25/2012] [Indexed: 01/14/2023]
Abstract
Hepatitis B remains a major global health problem despite the availability of a safe and effective vaccine. Segments of the population lack access to or respond poorly to the parenteral vaccine, perpetuating the infection-transmission cycle. A low cost, orally delivered vaccine has the potential to alleviate many of these problems. Here we describe the expression of a bioencapsulated hepatitis B surface antigen (HBsAg) in maize and its immunogenicity, demonstrating for the first time a commercially feasible oral subunit vaccine production system for a major disease. This work surmounts previous barriers to plant-produced vaccines by expressing HBsAg at much higher levels and retaining antigen immunogenicity post-processing: factors which facilitated a robust immune response in mice without the need for an adjuvant. This method provides a practical solution to the delivery of a low-cost, stable oral vaccine.
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Affiliation(s)
- Celine A Hayden
- Applied Biotechnology Institute, Cal Poly Tech Park, San Luis Obispo, CA 93407, United States
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Leonardi S, Vitaliti G, Garozzo MT, Miraglia del Giudice M, Marseglia G, La Rosa M. Hepatitis B vaccination failure in children with diabetes mellitus? The debate continues. Hum Vaccin Immunother 2012; 8:448-52. [PMID: 22370513 DOI: 10.4161/hv.19107] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND The aim of our study was to evaluate the presence of specific antibodies against HBsAg in diabetic children (IDDM) previously vaccinated against hepatitis B virus. PATIENTS AND METHODS 110 diabetic children were retrospectively studied and 100 healthy controls were recruited. In all patients surface antigen, HBV core IgG, antibodies against HBV "e" antigen and quantitative HBV surface antibodies were detected. In 45 patients molecular typing of HLA alleles was performed. Metabolic control was evaluated as mean glycated hemoglobin (HbA1c) and all patients were compliant to insulin therapy. RESULTS 46 of 110 diabetic children (41.8%) and 16 of 100 healthy controls (16%) were found to have not anti-HBs antibodies (p < 0.0001). The mean antibody titer was found significantly-lower (p < 0.0001) in IDDM children than healthy controls. No correlation was found between antibody titer, age, duration of disease and HbA1c. We did not find any difference of gender, age, years of onset of the disease and metabolic control, between diabetics with anti-HBs antibodies and those without. CONCLUSIONS Our data confirm the reduced seroprotection rate for HBV vaccination in diabetics. However it remains poorly clarify the real clinical significance of this result. In our study no diabetic children showed markers of HBV infection.
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New Hepatitis B Vaccine Schedule for Children with Celiac Disease. HEPATITIS MONTHLY 2011. [DOI: 10.5812/kowsar.1735143x.1105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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Ertekin V, Tosun MS, Selimoglu MA. Is there need for a new hepatitıs B vaccine schedule for children with celiac disease? HEPATITIS MONTHLY 2011. [PMID: 22140387 DOI: 10.5812/kowsar.1735143x.1129] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
BACKGROUND Celiac disease (CD) is an autoimmune disease characterized by immunemediated inflammatory damage of the small intestinal mucosa, precipitated by the ingestion of gluten-containing foods. Since human leucocyte antigen DQ2 (HLA-DQ2) is a marker of nonresponsiveness to hepatits B virus (HBV) vaccine, CD may also be associated with this nonresponsiveness. OBJECTIVES The aim of this study was to compare the responses to HBV vaccine between children with CD and healthy children. We also investigated the relationship between the patients' responses to hepatitis B vaccine, the clinical presentation of CD, and dietary compliance in the patients. PATIENTS AND METHODS We recruited 52 children with CD and 20 age- and sex-matched healthy children who received HBV vaccination according to the standard immunization schedule. The production of specific antihepatitis B surface antigen (HBsAg) antibodies was evaluated in all patients and control participants. Subjects with less than 10 IU/L anti-HBs were consided nonresponders to the vaccination. RESULTS 31 of the 52 patients (59.6%) were female and 21 (40.4%) were male. The mean age of the CD patients was 10.7 ± 4 years (range, 4-18 years). Anti-HBs titers were positive in 32 (61.5%) patients and negative in 20 (38.5%) patients, while they were positive in 18 (90%) of the children in the control group (P < 0.05). We found statistically significant differences between negative anti-HBs titers, clinical presentation of CD, and dietary compliance in patients with CD (P < 0.05). CONCLUSIONS Nonresponsiveness to hepatitis B vaccination was more frequently found in children with CD than in the control group. Therefore, the response to HBV vaccination should be investigated in children with CD, and a different immunization schedule may need to be developed. Further, compliance to the prescribed gluten-free diet (GFD) may improve the immune response to HBV vaccination in children with CD.
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Affiliation(s)
- Vildan Ertekin
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Istanbul Faculty of Medical Sciences, Istanbul University, Istanbul, Turkey
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Leonardi S, Vitaliti G, Pratico’ A, Pecoraro R, Rosa ML. A Retrospective Study on Standard Regimen for Vaccination in Celiac Children. ACTA ACUST UNITED AC 2011. [DOI: 10.4236/wjv.2011.12006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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Zingone F, Morisco F, Zanetti A, Romanò L, Portella G, Capone P, Andreozzi P, Tortora R, Ciacci C. Long-term antibody persistence and immune memory to hepatitis B virus in adult celiac patients vaccinated as adolescents. Vaccine 2010; 29:1005-8. [PMID: 21129395 DOI: 10.1016/j.vaccine.2010.11.060] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2010] [Revised: 11/09/2010] [Accepted: 11/16/2010] [Indexed: 12/21/2022]
Abstract
Aim of this study was to investigate the anti-HBs antibody persistence and immune memory to hepatitis B virus in adult celiacs vaccinated as adolescents and the effect of a booster administration in non-protected individuals. Eleven years after primary vaccination, the proportion of vaccinees with titres ≥ 10 mIU/ml and antibody geometric mean concentrations (GMCs) were lower among celiac patients than among controls (68.6% vs 91.7%, p<0.01; GMCs 29.38 mIU/ml vs 250.6 mIU/ml, p<0.001). Participants with anti-HBs below 10 mIU/ml received a booster dose and were retested 2 weeks later to assess the anamnestic response. Post-booster anti-HBs levels were still <10 mIU/ml in 71.4% celiacs and 25% controls (p<0.01). Our findings indicate that the prevalence of seroprotective levels of anti-HBs detected eleven years after primary immunization as well as the frequency of response to a booster dose of vaccine are lower in celiac patients compared to healthy controls.
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Affiliation(s)
- F Zingone
- Department of Clinical and Experimental Medicine, Federico II University of Naples, Italy
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Hepatitis B vaccine administered by intradermal route in patients with celiac disease unresponsive to the intramuscular vaccination schedule: a pilot study. Am J Gastroenterol 2010; 105:2117-9. [PMID: 20818367 DOI: 10.1038/ajg.2010.195] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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