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Motta RV, Culver EL. IgG4 autoantibodies and autoantigens in the context of IgG4-autoimmune disease and IgG4-related disease. Front Immunol 2024; 15:1272084. [PMID: 38433835 PMCID: PMC10904653 DOI: 10.3389/fimmu.2024.1272084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 01/25/2024] [Indexed: 03/05/2024] Open
Abstract
Immunoglobulins are an essential part of the humoral immune response. IgG4 antibodies are the least prevalent subclass and have unique structural and functional properties. In this review, we discuss IgG4 class switch and B cell production. We review the importance of IgG4 antibodies in the context of allergic responses, helminth infections and malignancy. We discuss their anti-inflammatory and tolerogenic effects in allergen-specific immunotherapy, and ability to evade the immune system in parasitic infection and tumour cells. We then focus on the role of IgG4 autoantibodies and autoantigens in IgG4-autoimmune diseases and IgG4-related disease, highlighting important parallels and differences between them. In IgG4-autoimmune diseases, pathogenesis is based on a direct role of IgG4 antibodies binding to self-antigens and disturbing homeostasis. In IgG4-related disease, where affected organs are infiltrated with IgG4-expressing plasma cells, IgG4 antibodies may also directly target a number of self-antigens or be overexpressed as an epiphenomenon of the disease. These antigen-driven processes require critical T and B cell interaction. Lastly, we explore the current gaps in our knowledge and how these may be addressed.
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Affiliation(s)
- Rodrigo V. Motta
- Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Emma L. Culver
- Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
- Department of Gastroenterology and Hepatology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
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Murata Y, Haneda M, Miyakawa N, Nishida S, Kajihara N, Maeda S, Ono K, Hanatani S, Igata M, Takaki Y, Motoshima H, Kishikawa H, Araki E. Autoimmune Polyglandular Syndrome Type 3 Complicated with IgG4-related Disease. Intern Med 2024; 63:425-431. [PMID: 37344441 PMCID: PMC10901709 DOI: 10.2169/internalmedicine.1270-22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/23/2023] Open
Abstract
A 52-year-old Japanese woman developed type 1 diabetes mellitus (type 1 DM) at 41 years old. She became complicated with Hashimoto's disease and showed swelling of both submandibular glands, which was diagnosed as IgG4-related disease (IgG4-RD). This is a rare case of a Japanese patient with autoimmune polyglandular syndrome type 3A (APS-3A) coexisting with autoimmune thyroid disease (AITD) and type 1 DM complicated by IgG4-RD. Bilateral submandibular gland resection was successfully performed without steroid therapy. We discuss the possibility that the immunological pathogenic mechanisms of APS-3A and IgG4-RD are related.
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Affiliation(s)
- Yusuke Murata
- Department of Diabetes, Metabolism and Endocrinology, Kumamoto University Hospital, Japan
| | - Masaki Haneda
- Department of Diabetes, Metabolism and Endocrinology, Kumamoto University Hospital, Japan
| | - Nobukazu Miyakawa
- Department of Diabetes, Metabolism and Endocrinology, Kumamoto University Hospital, Japan
| | - Saiko Nishida
- Department of Diabetes, Metabolism and Endocrinology, Kumamoto University Hospital, Japan
| | - Nobuhiro Kajihara
- Department of Diabetes, Metabolism and Endocrinology, Kumamoto University Hospital, Japan
| | - Sarie Maeda
- Department of Diabetes, Metabolism and Endocrinology, Kumamoto University Hospital, Japan
| | - Kaoru Ono
- Department of Metabolic Medicine, Faculty of Life Science, Kumamoto University, Japan
| | - Satoko Hanatani
- Department of Metabolic Medicine, Faculty of Life Science, Kumamoto University, Japan
| | - Motoyuki Igata
- Department of Metabolic Medicine, Faculty of Life Science, Kumamoto University, Japan
| | | | | | | | - Eiichi Araki
- Department of Metabolic Medicine, Faculty of Life Science, Kumamoto University, Japan
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He JY, Li J, Zhang YY, He HB, He YM, Xu DX, Wang X, Wu HY, Zhang JH, Jahid H, Sadia A, Yu HF, Wang JZ, Zou K. Tormentic acid, a triterpenoid isolated from the fruits of Chaenomeles speciose, protected indomethacin-induced gastric mucosal lesion via modulating miR-139 and the CXCR4/CXCL12/PLC/PKC/Rho a/MLC pathway. PHARMACEUTICAL BIOLOGY 2023; 61:1343-1363. [PMID: 37623313 PMCID: PMC10461523 DOI: 10.1080/13880209.2023.2249526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Revised: 07/31/2023] [Accepted: 08/14/2023] [Indexed: 08/26/2023]
Abstract
CONTEXT Tormentic acid (TA), an effective triterpenoid isolated from Chaenomeles speciosa (Sweet) Nakai (Rosaceae) fruits, exerts an effective treatment for gastric damage. OBJECTIVE To investigate the gastroprotective effect of TA on indomethacin (IND) damaged GES-1 cells and rats, and explore potential mechanisms. MATERIALS AND METHODS TA concentrations of 1.563-25 µM were used. Cell proliferation, apoptosis and migration were performed using MTT, colony formation, wound healing, migration, Hoechst staining assays. SD rats were divided into control, IND, TA (1, 2 and 4 mg/kg) + IND groups, once a day for 21 continuous days. Twenty-four hours after the last administration, all groups except the control group were given IND (100 mg/kg) by gavage. Gastric juice parameters, gastric ulcer, gastric blood flow (GBF), blood biochemical parameters and cytokine analysis and gastric mucosal histopathology were detected for 2 h and 6 h after IND oral administration. The mRNA and protein expression of miR-139 and the CXCR4/CXCL12/PLC/PKC/Rho A/MLC pathway were analyzed in the IND-damaged GES-1 cells and gastric tissue of rats. RESULTS TA might ameliorate the gastric mucosal injury by accelerating the IND-damaged GES-1 cell proliferation and migration, ameliorating GBF, ulcer area and pathologic changes, the redox system and cytokine levels, the gastric juice parameters, elevating the gastric pH in IND damaged rats; suppressed miR-139 mRNA expression, elevated CXCR4 and CXCL12 mRNA and protein expression, p-PLC, p-PKC, Rho A, MLCK and p-MLC protein expression. DISCUSSION AND CONCLUSIONS TA may have potential use as a clinical drug candidate for gastric mucosal lesion treatment.
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Affiliation(s)
- Jun-Yu He
- Department of Clinical Medicine, College of Basic Medical Science, China Three Gorges University, Yichang, P.R. China
| | - Jie Li
- Yichang Key Laboratory of Development and Utilization of Health Products with Drug Food Homology & Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang, P.R. China
| | - Yuan-Yuan Zhang
- Yichang Key Laboratory of Development and Utilization of Health Products with Drug Food Homology & Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang, P.R. China
| | - Hai-Bo He
- Yichang Key Laboratory of Development and Utilization of Health Products with Drug Food Homology & Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang, P.R. China
- Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Shiyan, P.R. China
| | - Yu-Min He
- Department of Clinical Medicine, College of Basic Medical Science, China Three Gorges University, Yichang, P.R. China
| | - Dao-Xiang Xu
- Department of Gastroenterology, Seventh People’s Hospital of Wenzhou, Wenzhou, P.R. China
| | - Xiao Wang
- Yichang Key Laboratory of Development and Utilization of Health Products with Drug Food Homology & Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang, P.R. China
| | - Hao-Yang Wu
- Department of Clinical Medicine, College of Basic Medical Science, China Three Gorges University, Yichang, P.R. China
| | - Ji-Hong Zhang
- Department of Gastroenterology, Chinese Medicine Clinical Medical College & Hubei Clinical Research Center for Functional Digestive Diseases of Traditional Chinese Medicine, China Three Gorges University, Yichang, P.R. China
| | - Hasan Jahid
- Yichang Key Laboratory of Development and Utilization of Health Products with Drug Food Homology & Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang, P.R. China
| | - Akter Sadia
- Yichang Key Laboratory of Development and Utilization of Health Products with Drug Food Homology & Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang, P.R. China
| | - Hui-Fan Yu
- Hubei Key Laboratory of Wudang Local Chinese Medicine Research, Shiyan, P.R. China
| | - Jun-Zhi Wang
- Yichang Key Laboratory of Development and Utilization of Health Products with Drug Food Homology & Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang, P.R. China
| | - Kun Zou
- Yichang Key Laboratory of Development and Utilization of Health Products with Drug Food Homology & Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University, Yichang, P.R. China
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Landry RL, Embers ME. The Probable Infectious Origin of Multiple Sclerosis. NEUROSCI 2023; 4:211-234. [PMID: 39483197 PMCID: PMC11523707 DOI: 10.3390/neurosci4030019] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 08/17/2023] [Accepted: 08/25/2023] [Indexed: 11/03/2024] Open
Abstract
Multiple sclerosis (MS) is an immune inflammatory disease that causes demyelination of the white matter of the central nervous system. It is generally accepted that the etiology of MS is multifactorial and believed to be a complex interplay between genetic susceptibility, environmental factors, and infectious agents. While the exact cause of MS is still unknown, increasing evidence suggests that disease development is the result of interactions between genetically susceptible individuals and the environment that lead to immune dysregulation and CNS inflammation. Genetic factors are not sufficient on their own to cause MS, and environmental factors such as viral infections, smoking, and vitamin D deficiency also play important roles in disease development. Several pathogens have been implicated in the etiology of MS, including Epstein-Barr virus, human herpesvirus 6, varicella-zoster virus, cytomegalovirus, Helicobacter pylori, Chlamydia pneumoniae, and Borrelia burgdorferi. Although vastly different, viruses and bacteria can manipulate host gene expression, causing immune dysregulation, myelin destruction, and neuroinflammation. This review emphasizes the pathogenic triggers that should be considered in MS progression.
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Affiliation(s)
- Remi L Landry
- Department of Tropical Medicine, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA;
- Division of Immunology, Tulane National Primate Research Center, Tulane University Health Sciences, Covington, LA 70433, USA
| | - Monica E Embers
- Department of Tropical Medicine, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA;
- Division of Immunology, Tulane National Primate Research Center, Tulane University Health Sciences, Covington, LA 70433, USA
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Kountouras J, Papaefthymiou A, Polyzos SA, Doulberis M. Potential Impact of Helicobacter pylori Infection on Pancreatic Cancer Pathophysiology. J Gastrointest Cancer 2023; 54:1014-1015. [PMID: 36471196 DOI: 10.1007/s12029-022-00897-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/28/2022] [Indexed: 12/12/2022]
Affiliation(s)
- Jannis Kountouras
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 54642, Thessaloniki, Macedonia, Greece.
| | - Apostolis Papaefthymiou
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 54642, Thessaloniki, Macedonia, Greece
- First Department of Pharmacology, Aristotle University of Thessaloniki, 54642, Thessaloniki, Macedonia, Greece
- Pancreaticobiliary Medicine Unit, University College London Hospitals (UCLH), London, UK
| | - Stergios A Polyzos
- First Department of Pharmacology, Aristotle University of Thessaloniki, 54642, Thessaloniki, Macedonia, Greece
| | - Michael Doulberis
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, 54642, Thessaloniki, Macedonia, Greece
- First Department of Pharmacology, Aristotle University of Thessaloniki, 54642, Thessaloniki, Macedonia, Greece
- Department of Gastroenterology and Hepatology, University of Zurich, 8091, Zurich, Switzerland
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Arjmandi D, Abdollahi A, Ardekani A, Razavian I, Razavian E, Sartip B, Mahjour S, Parsa H, Kyvanani NA, Marhoommirzabak E, Kountouras J, Rostami A. Helicobacter pylori infection and risk of multiple sclerosis: An updated meta-analysis. Helicobacter 2022; 27:e12927. [PMID: 36046943 DOI: 10.1111/hel.12927] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 08/14/2022] [Accepted: 08/19/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND There is considerable controversy around the question as to whether Helicobacter pylori (H. pylori) infection has a protective or causative role in the development of multiple sclerosis (MS). This study evaluated published information to assess the association between H. pylori infection and MS. METHODS We conducted a comprehensive systematic review of relevant observational studies in international databases. A random-effects model was used to calculate pooled odds ratio (OR) and 95% confidence interval (CI). I2 statistic was used to assess the between-study heterogeneity. Subgroup and meta-regression analyses were applied to identify the source of heterogeneity. RESULTS In total, 22 studies (25 datasets) were eligible for the meta-analysis: 17 datasets had prevalence data and eight datasets had data on the mean titer of anti-H. pylori IgG. The pooled prevalence of H. pylori was 44.1% (908/2606) in the MS patients and 46.1% (1016/2200) in the controls, indicating a non-significant protective effect of H. pylori on MS (OR, 0.82; 95%CI, 0.58-1.17). In the subgroup analysis, studies that used ELISA yielded a significant protective association (OR, 0.59; 95%CI, 0.46-0.77), while a positive non-significant association (OR, 1.33; 95%CI, 0.83-2.15) was found from studies that used other serological methods; interestingly, a significant positive association (OR, 6.64; 95%CI, 2.40-13.76) was found from studies that used histological methods to detect H. pylori infection. CONCLUSIONS Our findings do not support the hypothesis that H. pylori infection represents a protective factor against the development of MS; however, the results varied depending on the diagnostic method(s). Particularly, a significant positive association was identified when studies introduced results based on histological examination, suggesting that active H. pylori infection might be a risk factor for development of MS. Thus, further studies are needed utilizing accurate diagnostic methods to elucidate the association between active H. pylori infection and MS.
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Affiliation(s)
- Delaram Arjmandi
- Immunoregulation Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Ali Abdollahi
- Department of Surgery, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Ali Ardekani
- School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Iman Razavian
- Department of Neurosurgery, Functional Neurosurgery Research Center, Shohada Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Elnaz Razavian
- Department of Neurology, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Behnam Sartip
- Department of Internal Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Sanaz Mahjour
- Department of Psychiatry and Behavioral Sciences, Northwestern Feinberg School of Medicine, Chicago, Illinois, USA
| | - Hamid Parsa
- Department of Neurology, University of Visayas, Gullas College of Medicine, Cebu City, Philippines
| | - Nastaran Azizi Kyvanani
- Independent Researcher in the Field of Microbiology and Infectious Diseases, Erfurt, Germany
| | - Elika Marhoommirzabak
- Department of Neurology, University of Visayas, Gullas College of Medicine, Cebu City, Philippines
| | - Jannis Kountouras
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Ali Rostami
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
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Etchegaray-Morales I, Jiménez-Herrera EA, Mendoza-Pinto C, Rojas-Villarraga A, Macías-Díaz S, Osorio-Peña ÁD, Munguía-Realpozo P, García-Carrasco M. Helicobacter pylori and its association with autoimmune diseases: systemic lupus erythematosus, rheumatoid arthritis and Sjögren syndrome. J Transl Autoimmun 2021; 4:100135. [PMID: 34825158 PMCID: PMC8605081 DOI: 10.1016/j.jtauto.2021.100135] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2021] [Accepted: 11/12/2021] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a gram-negative bacterium that adapts to the gastric mucosa and provokes symptoms associated with gastritis. Chronic H. pylori infection in patients with a genetic predisposition can trigger autoimmune diseases due to the immune interaction of cellular and humoral responses. Infections are a triggering factor for systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren syndrome (SS), although the association between H. pylori and these diseases is unclear. Therefore, we reviewed this interaction and its clinical importance.
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Affiliation(s)
- Ivet Etchegaray-Morales
- Department of Rheumatology, Medicine School, Meritorious Autonomous University of Puebla, 13 Sur 2702, 72420, Puebla, Mexico
| | | | - Claudia Mendoza-Pinto
- Department of Rheumatology, Medicine School, Meritorious Autonomous University of Puebla, 13 Sur 2702, 72420, Puebla, Mexico
- Systemic Autoimmune Diseases Research, Unit of Specialties, Hospital UMAE, Mexican Social Security Institute, 2 Norte 2004, 72000, Puebla, Mexico
| | - Adriana Rojas-Villarraga
- Research Institute, Fundación Universitaria De Ciencias De La Salud, University of Health Sciences, Cra. 19 N 8a-32, Bogota, Colombia
| | - Salvador Macías-Díaz
- Internal Medicine Service, Hospital General de Zona N°1, Instituto Mexicano del Seguro Social, Avenida Francisco I. Madero 407, 42070, Hidalgo, Mexico
- Department of Medical Oncology. Medicine School. Meritorious Autonomous University of Puebla, 13 Sur 2702, 72420, Puebla, Mexico
| | - Ángel David Osorio-Peña
- Department of Rheumatology, Medicine School, Meritorious Autonomous University of Puebla, 13 Sur 2702, 72420, Puebla, Mexico
| | - Pamela Munguía-Realpozo
- Department of Rheumatology, Medicine School, Meritorious Autonomous University of Puebla, 13 Sur 2702, 72420, Puebla, Mexico
| | - Mario García-Carrasco
- Department of Rheumatology, Medicine School, Meritorious Autonomous University of Puebla, 13 Sur 2702, 72420, Puebla, Mexico
- Corresponding author.
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8
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Kunovsky L, Dite P, Jabandziev P, Dolina J, Vaculova J, Blaho M, Bojkova M, Dvorackova J, Uvirova M, Kala Z, Trna J. Helicobacter pylori infection and other bacteria in pancreatic cancer and autoimmune pancreatitis. World J Gastrointest Oncol 2021; 13:835-844. [PMID: 34457189 PMCID: PMC8371525 DOI: 10.4251/wjgo.v13.i8.835] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Revised: 03/24/2021] [Accepted: 07/05/2021] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is an infectious agent influencing as much as 50% of the world’s population. It is the causative agent for several diseases, most especially gastric and duodenal peptic ulcer, gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma of the stomach. A number of other, extragastric manifestations also are associated with H. pylori infection. These include neurological disorders, such as Alzheimer’s disease, demyelinating multiple sclerosis and Parkinson’s disease. There is also evidence for a relationship between H. pylori infection and such dermatological diseases as psoriasis and rosacea as well as a connection with infection and open-angle glaucoma. Generally little is known about the relationship between H. pylori infection and diseases of the pancreas. Most evidence about H. pylori and its potential role in the development of pancreatic diseases concerns pancreatic adenocarcinoma and autoimmune forms of chronic pancreatitis. There is data (albeit not fully consistent) indicating modestly increased pancreatic cancer risk in H. pylori-positive patients. The pathogenetic mechanism of this increase is not yet fully elucidated, but several theories have been proposed. Reduction of antral D-cells in H. pylori-positive patients causes a suppression of somatostatin secretion that, in turn, stimulates increased secretin secretion. That stimulates pancreatic growth and thus increases the risk of carcinogenesis. Alternatively, H. pylori, as a part of microbiome dysbiosis and the so-called oncobiome, is proven to be associated with pancreatic adenocarcinoma development via the promotion of cellular proliferation. The role of H. pylori in the inflammation characteristic of autoimmune pancreatitis seems to be explained by a mechanism of molecular mimicry among several proteins (mostly enzymes) of H. pylori and pancreatic tissue. Patients with autoimmune pancreatitis often show positivity for antibodies against H. pylori proteins. H. pylori, as a part of microbiome dysbiosis, also is viewed as a potential trigger of autoimmune inflammation of the pancreas. It is precisely these relationships (and associated equivocal conclusions) that constitute a center of attention among pancreatologists, immunologists and pathologists. In order to obtain clear and valid results, more studies on sufficiently large cohorts of patients are needed. The topic is itself sufficiently significant to draw the interest of clinicians and inspire further systematic research. Next-generation sequencing could play an important role in investigating the microbiome as a potential diagnostic and prognostic biomarker for pancreatic cancer.
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Affiliation(s)
- Lumir Kunovsky
- Department of Surgery, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic
- Department of Gastroenterology and Internal Medicine, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic
| | - Petr Dite
- Department of Gastroenterology and Internal Medicine, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic
- Department of Gastroenterology and Internal Medicine, University Hospital Ostrava, Ostrava 70800, Czech Republic
- Faculty of Medicine, University of Ostrava, Ostrava 70300, Czech Republic
| | - Petr Jabandziev
- Department of Pediatrics, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno 61300, Czech Republic
- Central European Institute of Technology, Masaryk University, Brno 62500, Czech Republic
| | - Jiri Dolina
- Department of Gastroenterology and Internal Medicine, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic
| | - Jitka Vaculova
- Department of Gastroenterology and Internal Medicine, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic
| | - Martin Blaho
- Department of Gastroenterology and Internal Medicine, University Hospital Ostrava, Ostrava 70800, Czech Republic
- Faculty of Medicine, University of Ostrava, Ostrava 70300, Czech Republic
| | - Martina Bojkova
- Department of Gastroenterology and Internal Medicine, University Hospital Ostrava, Ostrava 70800, Czech Republic
- Faculty of Medicine, University of Ostrava, Ostrava 70300, Czech Republic
| | - Jana Dvorackova
- Department of Intensive Medicine, Emergency Medicine and Forensic Studies, University Hospital Ostrava, Ostrava 70800, Czech Republic
- Faculty of Medicine, University of Ostrava, Ostrava 70300, Czech Republic
| | | | - Zdenek Kala
- Department of Surgery, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic
| | - Jan Trna
- Department of Gastroenterology and Internal Medicine, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno 62500, Czech Republic
- Department of Gastroenterology and Digestive Endoscopy, Masaryk Memorial Cancer Institute, Brno 65653, Czech Republic
- Department of Internal Medicine, Hospital Boskovice, Boskovice 68001, Czech Republic
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9
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Youssefi M, Tafaghodi M, Farsiani H, Ghazvini K, Keikha M. Helicobacter pylori infection and autoimmune diseases; Is there an association with systemic lupus erythematosus, rheumatoid arthritis, autoimmune atrophy gastritis and autoimmune pancreatitis? A systematic review and meta-analysis study. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2021; 54:359-369. [PMID: 32891538 DOI: 10.1016/j.jmii.2020.08.011] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Revised: 07/07/2020] [Accepted: 08/16/2020] [Indexed: 02/05/2023]
Affiliation(s)
- Masoud Youssefi
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohsen Tafaghodi
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hadi Farsiani
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Kiarash Ghazvini
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Masoud Keikha
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.
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10
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Review of Diagnostic Biomarkers in Autoimmune Pancreatitis: Where Are We Now? Diagnostics (Basel) 2021; 11:diagnostics11050770. [PMID: 33923064 PMCID: PMC8146865 DOI: 10.3390/diagnostics11050770] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 04/22/2021] [Accepted: 04/23/2021] [Indexed: 12/16/2022] Open
Abstract
Autoimmune pancreatitis (AIP) is a pancreatic manifestation of an IgG4-related disease (IgG4-RD). AIP lacks disease-specific biomarkers, and therefore, it is difficult to distinguish AIP from malignancies, especially pancreatic cancer. In this review, we have summarized the latest findings on potential diagnostic biomarkers for AIP. Many investigations have been conducted, but no specific biomarkers for AIP are identified. Therefore, further studies are required to identify accurate diagnostic biomarkers for AIP.
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11
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Floreani A, Okazaki K, Uchida K, Gershwin ME. IgG4-related disease: Changing epidemiology and new thoughts on a multisystem disease. J Transl Autoimmun 2020; 4:100074. [PMID: 33490938 PMCID: PMC7806798 DOI: 10.1016/j.jtauto.2020.100074] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 11/19/2020] [Accepted: 12/10/2020] [Indexed: 02/07/2023] Open
Abstract
IgG4-related disease (IgG4-RD) represents an immune-mediated fibroinflammatory condition with peculiar histopathologic changes that can affect various organs. In 2012 its unified nomenclature was published, which allows to abandon other synonymous names. Up to now, only little is known about its epidemiology around the world. However, although it is generally considered a rare condition, the number of patients with IgG4-RD is increasing enormously. Likewise, the annual number of publications on this subject has increased progressively. The spectrum of clinical manifestations in IgG4-RD is highly variable, depending on the severity of the disease as well as the presence of organ(s) involvement. This review gives an overview on changing epidemiology of IgG4-RD focusing the attention on the large cohorts of patients published in the literature.
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Affiliation(s)
- Annarosa Floreani
- Scientific Consultant IRCCS Negrar, Verona, Italy
- Senior Scholar, University of Padova, Italy
| | - Kazuichi Okazaki
- Department of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan
| | - Kazushige Uchida
- Department of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan
| | - M. Eric Gershwin
- Division of Rheumatology Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA, USA
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Kountouras J, Papaefthymiou A, Gavalas E, Polyzos SA, Boziki M, Kyriakou P, Katsinelos P, Zavos C, Liatsos C, Tzivras D, Tzitiridou-Chatzopoulou M, Dardiotis E, Deretzi G, Vardaka E, Doulberis M. Helicobacter pylori infection as a potential risk factor for multiple sclerosis. Med Hypotheses 2020; 143:110135. [DOI: 10.1016/j.mehy.2020.110135] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 06/28/2020] [Accepted: 07/22/2020] [Indexed: 02/07/2023]
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Kountouras J, Papaefthymiou A, Polyzos SA, Zavos C, Doulberis M. Letter to the editor re: Li et al. (2020), ‘The potential role of bacteria in pancreatic cancer: A systematic review’. Carcinogenesis 2020; 41:539-540. [DOI: 10.1093/carcin/bgaa042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2020] [Revised: 03/25/2020] [Accepted: 05/09/2020] [Indexed: 11/14/2022] Open
Affiliation(s)
- Jannis Kountouras
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Apostolis Papaefthymiou
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Stergios A Polyzos
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
- First Department of Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Macedonia, Greece
| | - Christos Zavos
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
| | - Michael Doulberis
- Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
- Department of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland
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Association between Active Helicobacter pylori Infection and Glaucoma: A Systematic Review and Meta-Analysis. Microorganisms 2020; 8:microorganisms8060894. [PMID: 32545826 PMCID: PMC7355761 DOI: 10.3390/microorganisms8060894] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 06/11/2020] [Accepted: 06/12/2020] [Indexed: 12/12/2022] Open
Abstract
Background: Glaucoma is the second most common cause of blindness worldwide affecting almost 70 million individuals. Helicobacter pylori (H. pylori) is a widespread pathogen with systematic pathogenicity. This meta-analysis aimed to estimate the contradictory data regarding a potential association between active H. pylori infection and glaucoma. Materials and Methods: A research in MEDLINE/PubMed and Google Scholar was conducted and original studies investigating the relationship between H. pylori infection and glaucoma were included. Analysis was performed with random effects model. The main outcome was the odds ratio (OR) with 95% confidence intervals (CI) of H. pylori infection as a risk factor for glaucoma. A parallel analysis studied the role of active infection as indicated by histology and the titer of anti-H. pylori antibodies. For the anti-H. pylori antibody titers, weighted mean differences (WMD) were estimated between patients and controls. Results: Fifteen studies were included, with 2664 participants (872 patients with glaucoma and 1792 controls), divided into primary open-angle glaucoma (POAG), normal tension glaucoma (NTG) and pseudo-exfoliation glaucoma (PEG). The association between H. pylori infection and overall glaucoma was significant (OR = 2.08, CI 95% 1.48–2.93) with moderate heterogeneity (I2 = 61.54%). After stratification by glaucoma subtype, heterogeneity was eliminated in the NTG subgroup. Studies with healthy controls, and controls with anemia yielded very low or no heterogeneity, respectively. Gastric biopsy to document active H. pylori infection yielded the highest OR (5.4, CI: 3.17–9.2, p < 0.001) and null heterogeneity. For anti-H. pylori antibody titers, there was a significant difference in WMD between patients and controls (WMD 15.98 IU/mL; 95% CI: 4.09–27.87; p = 0.008); values were greater in glaucoma patients, with high heterogeneity (I2: 93.8%). Meta-regression analysis showed that mean age had a significant impact on glaucoma (p = 0.037). Conclusions: Active H. pylori infection may be associated with glaucoma with null heterogeneity, as, beyond histology, quantified by anti-H. pylori titers and increases with age.
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Palanisamy S, Vinosha M, Manikandakrishnan M, Anjali R, Rajasekar P, Marudhupandi T, Manikandan R, Vaseeharan B, Prabhu NM. Investigation of antioxidant and anticancer potential of fucoidan from Sargassum polycystum. Int J Biol Macromol 2018; 116:151-161. [PMID: 29729339 DOI: 10.1016/j.ijbiomac.2018.04.163] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Revised: 04/02/2018] [Accepted: 04/29/2018] [Indexed: 01/10/2023]
Abstract
The present study was aimed to evaluate the antioxidant and anticancer potential of fucoidan isolated from Sargassum polycystum. The isolated fucoidan was successfully purified by DEAE cellulose-ion exchange chromatography and dialysis. Totally four active fractions (F1-F4) were collected and explored its chemical constitution by calorimetric assays. Among them, fraction 2 (F2) showed the higher yield percentage, fucose and sulphate content. Further, monosaccharide composition, structural and functional properties of the F2 was analyzed by HPLC, FTIR and NMR. F2 shows highest DPPH radical scavenging activity (55.94 ± 0.69%), reducing power (0.33 absorbance rate), hydrogen peroxide scavenging activity (71.76 ± 2.14%) and nitric oxide radical scavenging activity (51.81 ± 1.04%) at 1000 μg/ml. The cell viability of MCF-7 and HCT-15 cell lines was proportionate to the concentration of F2 with an estimated IC50 was 20 and 50 μg/ml respectively. The fluorescence and confocal laser scanning microscopic analysis demonstrated the apoptotic morphological changes and cell mediated death in F2 treated cancer cells. Higher amount of LDH release was found in the F2 treated cancer cells than the control group. Thus, the present finding proved that the isolated F2 encompasses significant antioxidant and anticancer property.
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Affiliation(s)
- Subramanian Palanisamy
- Disease control and Prevention Lab, Department of Animal Health and Management, Alagappa University, Karaikudi 630 004, Tamil Nadu, India
| | - Manoharan Vinosha
- Disease control and Prevention Lab, Department of Animal Health and Management, Alagappa University, Karaikudi 630 004, Tamil Nadu, India
| | - Muthushanmugam Manikandakrishnan
- Disease control and Prevention Lab, Department of Animal Health and Management, Alagappa University, Karaikudi 630 004, Tamil Nadu, India
| | - Ravichandran Anjali
- Disease control and Prevention Lab, Department of Animal Health and Management, Alagappa University, Karaikudi 630 004, Tamil Nadu, India
| | - Periyannan Rajasekar
- Disease control and Prevention Lab, Department of Animal Health and Management, Alagappa University, Karaikudi 630 004, Tamil Nadu, India
| | - Thangapandi Marudhupandi
- Biomaterials and Biotechnology in Animal Health Lab, Department of Animal Health and Management, Alagappa University, Karaikudi 630 004, Tamil Nadu, India
| | - Ramar Manikandan
- Department of Zoology, University of Madras, Guindy Campus, Chennai 600 025, Tamil Nadu, India
| | - Baskaralingam Vaseeharan
- Biomaterials and Biotechnology in Animal Health Lab, Department of Animal Health and Management, Alagappa University, Karaikudi 630 004, Tamil Nadu, India
| | - Narayanasamy Marimuthu Prabhu
- Disease control and Prevention Lab, Department of Animal Health and Management, Alagappa University, Karaikudi 630 004, Tamil Nadu, India.
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Detlefsen S, de Vos JD, Tanassi JT, Heegaard NHH, Fristrup C, Schaffalitzky de Muckadell OB. Value of anti-plasminogen binding peptide, anti-carbonic anhydrase II, immunoglobulin G4, and other serological markers for the differentiation of autoimmune pancreatitis and pancreatic cancer. Medicine (Baltimore) 2018; 97:e11641. [PMID: 30075546 PMCID: PMC6081052 DOI: 10.1097/md.0000000000011641] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The diagnosis of autoimmune pancreatitis (AIP) and its differential diagnosis from pancreatic cancer (PC) can be challenging. In this retrospective study, we aimed to evaluate the value of anti-plasminogen binding peptide (a-PBP), immunoglobulin G4 (IgG4), and anti-carbonic anhydrase-II (a-CA-II), together with other serological markers whose value is not fully elucidated.The serum levels of a-PBP, IgG4, IgG, anti-nuclear antibodies (ANA), anti-lactoferrin (a-LF), a-CA-II, and rheumatoid factor (RF) were evaluated in patients with AIP (n = 29), PC (n = 17), pancreatic neuroendocrine neoplasm (P-NEN, n = 12), and alcoholic chronic pancreatitis (ACP, n = 41). ANCA were measured in the AIP patients.There was no statistically significant difference in mean a-PBP values in AIP compared with PC. A ROC curve showed that, when using a cut-off of 38.3 U, low values of a-PBP had a sensitivity and specificity of 45% and 71% for differentiating AIP from PC. The sensitivity and specificity of IgG4 (cut-off 1.4 g/L) for differentiating AIP from PC was 45% and 88%, but rose to 52% and 88% when using a cut-off of 1.09 g/L. When using this cut-off, the sensitivity and specificity for differentiating type 1 AIP from PC was 68% and 88%. None of the other markers were significantly changed in AIP versus PC. For differentiation of type 1 and type 2 AIP, the only significant differences were IgG4 in type 1 AIP (P < .01), with a sensitivity of 68% and a specificity of 80%, and c-ANCA elevations found in some type 2 AIP patients (P < .05).The only serological marker for which we found a statistically significant difference in mean values between AIP and PC was IgG4. However, the value of IgG4 for the distinction of AIP from PC was limited, probably in part due to the relatively high number of type 2 AIP patients in our study. In accord with recent publications, our data do not support a role of increased serum a-PBP for the diagnosis of AIP.
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Affiliation(s)
- Sönke Detlefsen
- Department of Pathology
- Odense Pancreas Center (OPAC), Odense University Hospital
- Institute of Clinical Research, University of Southern Denmark
| | - Jesper D. de Vos
- Institute of Clinical Research, University of Southern Denmark
- Department of Medical Gastroenterology, Odense University Hospital, Odense
| | - Julia T. Tanassi
- Department of Autoimmunology and Biomarkers, Statens Serum Institute, Copenhagen
| | - Niels H. H. Heegaard
- Department of Autoimmunology and Biomarkers, Statens Serum Institute, Copenhagen
- Department of Clinical Biochemistry and Pharmacology
| | - Claus Fristrup
- Odense Pancreas Center (OPAC), Odense University Hospital
- Department of Surgery, Odense University Hospital, Odense, Denmark
| | - Ove B. Schaffalitzky de Muckadell
- Institute of Clinical Research, University of Southern Denmark
- Department of Medical Gastroenterology, Odense University Hospital, Odense
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Meng C, Bai C, Brown TD, Hood LE, Tian Q. Human Gut Microbiota and Gastrointestinal Cancer. GENOMICS PROTEOMICS & BIOINFORMATICS 2018. [PMID: 29474889 DOI: 10.1016/j.gpb.2017.06.002.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
Human gut microbiota play an essential role in both healthy and diseased states of humans. In the past decade, the interactions between microorganisms and tumors have attracted much attention in the efforts to understand various features of the complex microbial communities, as well as the possible mechanisms through which the microbiota are involved in cancer prevention, carcinogenesis, and anti-cancer therapy. A large number of studies have indicated that microbial dysbiosis contributes to cancer susceptibility via multiple pathways. Further studies have suggested that the microbiota and their associated metabolites are not only closely related to carcinogenesis by inducing inflammation and immune dysregulation, which lead to genetic instability, but also interfere with the pharmacodynamics of anticancer agents. In this article, we mainly reviewed the influence of gut microbiota on cancers in the gastrointestinal (GI) tract (including esophageal, gastric, colorectal, liver, and pancreatic cancers) and the regulation of microbiota by diet, prebiotics, probiotics, synbiotics, antibiotics, or the Traditional Chinese Medicine. We also proposed some new strategies in the prevention and treatment of GI cancers that could be explored in the future. We hope that this review could provide a comprehensive overview of the studies on the interactions between the gut microbiota and GI cancers, which are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, diagnosis, and treatment.
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Affiliation(s)
- Changting Meng
- Institute for Systems Biology, Seattle, WA 98109, USA; Department of Oncology, Peking Union Medical College Hospital, Beijing 100730, China
| | - Chunmei Bai
- Department of Oncology, Peking Union Medical College Hospital, Beijing 100730, China
| | | | - Leroy E Hood
- Institute for Systems Biology, Seattle, WA 98109, USA; Swedish Cancer Institute, Seattle, WA 98104, USA
| | - Qiang Tian
- Institute for Systems Biology, Seattle, WA 98109, USA; P4 Medicine Institute, Seattle, WA 98109, USA.
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Meng C, Bai C, Brown TD, Hood LE, Tian Q. Human Gut Microbiota and Gastrointestinal Cancer. GENOMICS, PROTEOMICS & BIOINFORMATICS 2018; 16:33-49. [PMID: 29474889 PMCID: PMC6000254 DOI: 10.1016/j.gpb.2017.06.002] [Citation(s) in RCA: 260] [Impact Index Per Article: 37.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/08/2017] [Revised: 06/08/2017] [Accepted: 07/04/2017] [Indexed: 02/06/2023]
Abstract
Human gut microbiota play an essential role in both healthy and diseased states of humans. In the past decade, the interactions between microorganisms and tumors have attracted much attention in the efforts to understand various features of the complex microbial communities, as well as the possible mechanisms through which the microbiota are involved in cancer prevention, carcinogenesis, and anti-cancer therapy. A large number of studies have indicated that microbial dysbiosis contributes to cancer susceptibility via multiple pathways. Further studies have suggested that the microbiota and their associated metabolites are not only closely related to carcinogenesis by inducing inflammation and immune dysregulation, which lead to genetic instability, but also interfere with the pharmacodynamics of anticancer agents. In this article, we mainly reviewed the influence of gut microbiota on cancers in the gastrointestinal (GI) tract (including esophageal, gastric, colorectal, liver, and pancreatic cancers) and the regulation of microbiota by diet, prebiotics, probiotics, synbiotics, antibiotics, or the Traditional Chinese Medicine. We also proposed some new strategies in the prevention and treatment of GI cancers that could be explored in the future. We hope that this review could provide a comprehensive overview of the studies on the interactions between the gut microbiota and GI cancers, which are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, diagnosis, and treatment.
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Affiliation(s)
- Changting Meng
- Institute for Systems Biology, Seattle, WA 98109, USA; Department of Oncology, Peking Union Medical College Hospital, Beijing 100730, China
| | - Chunmei Bai
- Department of Oncology, Peking Union Medical College Hospital, Beijing 100730, China
| | | | - Leroy E Hood
- Institute for Systems Biology, Seattle, WA 98109, USA; Swedish Cancer Institute, Seattle, WA 98104, USA
| | - Qiang Tian
- Institute for Systems Biology, Seattle, WA 98109, USA; P4 Medicine Institute, Seattle, WA 98109, USA.
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OKAZAKI K, UCHIDA K. Current perspectives on autoimmune pancreatitis and IgG4-related disease. PROCEEDINGS OF THE JAPAN ACADEMY. SERIES B, PHYSICAL AND BIOLOGICAL SCIENCES 2018; 94:412-427. [PMID: 30541967 PMCID: PMC6374139 DOI: 10.2183/pjab.94.027] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/12/2023]
Abstract
IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder recognized as a novel clinical entity with either synchronous or metachronous multi-organ involvement. Patients with IgG4-RD show diffuse or focal organ enlargement and mass-forming or nodular/thickened lesions with abundant infiltration of IgG4-positive plasmacytes and fibrosis, and such patients respond well to steroid treatment. It should be differentiated from mimics by a combination of serum IgG4 level, imaging features, and histopathological findings. The current first-line drug is corticosteroids, or rituximab in high-risk patients for steroid intolerance. Although relapse rates are high, standardized protocols for relapsed cases have not been approved yet. Based on genetic factors, disease-specific or -related antigens, abnormal innate and adaptive immunity may be involved, although the precise pathogenic mechanism and long-term outcome still remain unclear.
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Affiliation(s)
- Kazuichi OKAZAKI
- Department of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan
- Correspondence should be addressed: K. Okazaki, Department of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan (e-mail: )
| | - Kazushige UCHIDA
- Department of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan
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Culver EL, Smit WL, Evans C, Sadler R, Cargill T, Makuch M, Wang LM, Ferry B, Klenerman P, Barnes E. No evidence to support a role for Helicobacter pylori infection and plasminogen binding protein in autoimmune pancreatitis and IgG4-related disease in a UK cohort. Pancreatology 2017; 17:395-402. [PMID: 28412148 PMCID: PMC5459459 DOI: 10.1016/j.pan.2017.04.002] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Revised: 04/02/2017] [Accepted: 04/04/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND OBJECTIVES Helicobacter pylori (H.pylori) plasminogen binding protein (PBP) has been proposed as an antigen triggering autoimmune pancreatitis (AIP), the pancreatic manifestation of IgG4-related disease (IgG4-RD). We investigated exposure to H. pylori infection, cytokine response and immunological memory to H. pylori PBP in a prospective IgG4-RD cohort in the UK. METHODS Clinical and endoscopic evidence of peptic ulceration, serological H. pylori exposure and serum IgG4 levels were obtained in 55 IgG4-RD patients and 52 disease controls (DC) with autoimmune or inflammatory conditions with an elevated serum IgG4. Gastric and duodenal tissues were assessed for H. pylori and immunostained for IgG4. B and T cell ELISpot and cytokine luminex assays were used to detect immune responses to H. pylori PBP. RESULTS 85% of IgG4-RD patients had pancreatic and/or biliary disease, 89% had extra-pancreatic manifestations, and 84% had an increased serum IgG4. Clinical dyspepsia (35.2%), gastritis (58%), peptic ulceration (7.4%) and H. pylori colonisation (24%) in IgG4-RD was similar to DC. In IgG4-RD, gastric tissue contained a chronic inflammatory infiltrate with a low IgG4+ plasma-cell count (<10/HPF; range 1-4/HPF), and duodenal specimens had an increased IgG4 count (>10/HPF; range 7-54) compared with DC (p < 0.01). Th1 and Th2 cytokine response and immunological B-cell memory to H. pylori PBP did not differ between IgG4-RD and DC. CONCLUSIONS In a prospective UK cohort, the prevalence of gastric ulceration, exposure to H. pylori, cytokine response and immunological memory to H. pylori PBP did not differ in IgG4-RD patients compared with DC. This study does not support a role for H. pylori PBP as a microbial antigen in IgG4-RD. KEYWORDS FOR ABSTRACT Peptic ulceration, Antigens, B cells, T cells, Interleukins, Helicobacter pylori.
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Affiliation(s)
- Emma L Culver
- Peter Medawar Building, Nuffield Department Medicine, Oxford University, UK; Translational Gastroenterology Unit and NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK.
| | - Wouter L Smit
- Translational Gastroenterology Unit and NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK; Academic Medical Centre, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands
| | - Caroline Evans
- Clinical Immunology Department, Churchill Hospital, Oxford, UK
| | - Ross Sadler
- Clinical Immunology Department, Churchill Hospital, Oxford, UK
| | - Tamsin Cargill
- Peter Medawar Building, Nuffield Department Medicine, Oxford University, UK; Translational Gastroenterology Unit and NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK
| | - Mateusz Makuch
- Peter Medawar Building, Nuffield Department Medicine, Oxford University, UK
| | - Lai-Mun Wang
- Department of Cellular Pathology, John Radcliffe Hospital, Oxford, UK
| | - Berne Ferry
- Clinical Immunology Department, Churchill Hospital, Oxford, UK
| | - Paul Klenerman
- Peter Medawar Building, Nuffield Department Medicine, Oxford University, UK; Translational Gastroenterology Unit and NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK
| | - Eleanor Barnes
- Peter Medawar Building, Nuffield Department Medicine, Oxford University, UK; Translational Gastroenterology Unit and NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK
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Overview of IgG4 - Related Disease. J Med Life 2017; 10:203-207. [PMID: 29362594 PMCID: PMC5771249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Rationale (hypothesis): IgG4-related disease (IgG4-RD) is a pathological entity recently recognized by the medical world that can affect any organ or system. However, there is insufficient data about this disease in medical literature. Aim (objective): A more extensive clarification of the IgG4 molecule, the diversified aspects of IgG4-related disease, and the response of this disease to treatment, will provide a crucial understanding of the immune system and other diseases now known to be associated with IgG4. METHODS AND RESULTS The MEDLINE online medical database was used, and, after a comprehensive review of medical articles regarding IgG4-RD, published after 2003, using the search words "IgG4- related disease" and "IgG4 molecule", we have described the clinical, pathological and therapeutic features of IgG4-RD, as well as the presence of the IgG4 molecule in the evolution, diagnosis and management of this syndrome. We characterized the potential disease mechanisms and discussed early observations related to treatment. DISCUSSION Given the response to immunosuppressive therapy, it is hypothesized that IgG4-related disease is most likely an autoimmune disease. Therefore, IgG4-related disease is a fibro-inflammatory condition that can affect any organ and can lead to the formation of pseudotumoral lesions requiring differential diagnosis with various malignancies. Positive diagnostic criteria are histopathological and require at least two features out of the following three: dense limphoplasmocitary infiltrate, storiform fibrosis, obliterative phlebitis.
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Testing for Anti-PBP Antibody Is Not Useful in Diagnosing Autoimmune Pancreatitis. Am J Gastroenterol 2016; 111:1650-1654. [PMID: 27325222 DOI: 10.1038/ajg.2016.241] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Accepted: 05/11/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis, clinically mimicking pancreatic cancer. In 2009, a serological diagnostic test detecting antibodies against plasminogen-binding protein (PBP) of Helicobacter pylori was reported with outstanding test performances (NEJM 361:135). We aimed to validate these findings. METHODS Between March 2007 and May 2011, sera were collected from consecutive patients presenting with type 1 AIP, pancreatic ductal adenocarcinoma (PDAC), chronic pancreatitis (CP), primary sclerosing cholangitis (PSC), and healthy controls (HC) with or without antibodies against H. pylori. Serum antibody binding to synthetic PBP peptide was quantified by enzyme-linked immunosorbent assay (ELISA), using standard curves of custom-made PBP rabbit polyclonal antibodies. A synthetic Flag peptide (DYKDDDK), to which no antibodies are found in human serum, was included as negative control. RESULTS High sensitivity of PBP peptide recognition was demonstrated by selective binding of PBP peptide over Flag peptide by PBP-immunized rabbit serum. Competition assays with PBP peptide validated the selectivity for antibodies recognizing this antigen. A total of 114 patients were subsequently tested: 34 AIP, 29 PDAC, 17 CP, 16 PSC, and 18 HCs (9 positive and 9 negative for H. pylori). No significant differences in detection of antibodies against the PBP peptide were found between different the patient groups and healthy controls. CONCLUSIONS Using a sensitive and selective ELISA-based assay, we did not find increased serum antibodies against PBP peptide in AIP patients. PBP serum antibodies are therefore not a useful diagnostic tool to diagnose AIP.
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Abstract
IgG4-related hepatobiliary diseases are part of a multiorgan fibroinflammatory condition termed IgG4-related disease, and include IgG4-related sclerosing cholangitis (IgG4-SC) and IgG4-related hepatopathy. These diseases can present with biliary strictures and/or mass lesions, making them difficult to differentiate from primary sclerosing cholangitis (PSC) or other hepatobiliary malignancies. Diagnosis is based on a combination of clinical, biochemical, radiological and histological findings. However, a gold standard diagnostic test is lacking, warranting the identification of more specific disease markers. Novel assays - such as the serum IgG4:IgG1 ratio and IgG4:IgG RNA ratio (which distinguish IgG4-SC from PSC with high serum IgG4 levels), and plasmablast expansion to recognize IgG4-SC with normal serum IgG4 levels - require further validation. Steroids and other immunosuppressive therapies can lead to clinical and radiological improvement when given in the inflammatory phase of the disease, but evidence for the efficacy of treatment regimens is limited. Progressive fibrosclerotic disease, liver cirrhosis and an increased risk of malignancy are now recognized outcomes. Insights into the genetic and immunological features of the disease have increased over the past decade, with an emphasis on HLAs, T cells, circulating memory B cells and plasmablasts, chemokine-mediated trafficking, as well as the role of the innate immune system.
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Cheng C, Li CP. Influence of Helicobacter pylori infection on extra-gastric diseases. Shijie Huaren Xiaohua Zazhi 2016; 24:2010-2018. [DOI: 10.11569/wcjd.v24.i13.2010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The discovery of Helicobacter pylori (H. pylori) colonization of the stomach and its pathogenic effects is a crucial landmark in modern gastroenterology. There have been many studies reporting that the natural history of many disorders of the upper gastrointestinal tract, such as chronic gastritis, peptic ulcer disease, gastric cancer and MALT lymphoma are linked with the presence of this bacterium. Moreover, H. pylori is often involved in the pathogenic processes of a variety of extra-gastric diseases, especially those characterized by persistent and low grade systemic inflammation. The proposed mechanisms ranging from the induction of a low grade inflammatory state to the occurrence of molecular mimicry mechanisms. This paper will review the results of the most important studies on the association of H. pylori infection with extra-gastric diseases, such as autoimmune, neoplastic, cardiovascular and other related disorders, as well as possible mechanisms implicated in the pathogenesis of these extra-gastric diseases.
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Smit WL, Culver EL, Chapman RW. New Thoughts on Immunoglobulin G4-Related Sclerosing Cholangitis. Clin Liver Dis 2016; 20:47-65. [PMID: 26593290 DOI: 10.1016/j.cld.2015.08.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Immunoglobulin G4 (IgG4)-related sclerosing cholangitis (IgG4-SC) is the biliary manifestation of the multisystem IgG4-related disease. IgG4-SC presents with biliary strictures and/or masses that can bear a striking similarity to other malignant and inflammatory diseases. Diagnosis is based on a combination of clinical, biochemical, radiological, and histologic findings with careful exclusion of malignant disease. Corticosteroids are the mainstay of treatment with good clinical, biochemical, and radiological responses. This review provides a comprehensive overview of the current knowledge of the prevalence, clinical features, radiology and histology findings, diagnosis, treatment, natural history, and pathophysiology of IgG4-SC.
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Affiliation(s)
- Wouter L Smit
- Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Amsterdam 1105 AZ, The Netherlands; Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK
| | - Emma L Culver
- Translational Gastroenterology Unit, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK; Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK
| | - Roger W Chapman
- Translational Gastroenterology Unit, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK; Nuffield Department of Medicine, University of Oxford, Old Road Campus, Oxford OX3 7BN, UK.
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Abstract
Helicobacter pylori (H. pylori) is confirmed to be associated with many diseases such as gastric cancer, peptic ulcer, gastritis and mucosa-associated lymphoid tissue lymphoma. Recent studies found that H. pylori is associated with many extra-gastric diseases. The underlying mechanism involves autoimmunity, inflammation and oxidative stress. Here we review the association between H. pylori and extra-gastric diseases.
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Nasrat RM, Nasrat MM, Nasrat AM, Nasrat SA. Improvement of Idiopathic Cardiomyopathy After Colon Clear. Cardiol Res 2015; 6:249-254. [PMID: 28197234 PMCID: PMC5295537 DOI: 10.14740/cr398e] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/08/2015] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND The study aimed to illustrate the effect of colon clear on idiopathic myocardial dysfunction. Helicobacter pylori colonized the stomach since an immemorial time, as if both the stomach and the bacterium used to live together in peace harmless to each other. H. pylori could migrate or get forced to migrate to the colon; antibiotics are seldom effective against extra-gastric H. pylori strains. The association of H. pylori and some cardiovascular diseases like myocarditis and cardiomyopaty has been sufficiently mentioned in literature. The role played by the increased mucosal production of inflammatory mediators (cytokines) induced by H. pylori among patients with ischemic heart diseases has been also clearly illustrated. The clinical association of gastritis and carditis is controversial. Active lymphocytic myocarditis manifested by intractable ventricular tachycardia, non-specific intra-ventricular block, and myocardial dysfunction has been described in a young woman infected with H. pylori; an immune influence has been emphasized in that patient as a possible etiology behind the development of autoimmune myocarditis. It has been reported also in literature that a possible role of autoimmunity induced by H. pylori in cardiomyopathy cannot be excluded. METHODS Three female patients with frank history of H. pylori dyspepsia and an age range of 41 - 47 years have developed myocaditis complicated with cardiomyopathy as confirmed by echocardiography (ECG) and magnetic resonance imaging (MRI). Existence of H. pylori in the colon was confirmed by H. pylori fecal antigen. Colon clear was done for them. RESULTS Symptomatic improvement and clinical recovery to sinus rhythm with minimal supra-ventricular extra-systoles occurred for all patients after colon clear. Patients continued improvement to normal cardiac tracing and normal left ventricular ejection function within further 3 - 4 weeks. CONCLUSION Colon clear could be a simple and safe measure to improve changes in cardiac rhythm, heart rate and myocardial function developing in association with H. pylori due to inflammatory, toxic or immune reasons.
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Affiliation(s)
- Randa M Nasrat
- Department of Internal Medicine, Helwan Gen Hosp, Cairo, Egypt
| | | | | | - Salwa A Nasrat
- Department of Physiotherapy, Cardiac Surgery Academy, Cairo, Egypt
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Mitsuyama T, Uchida K, Sumimoto K, Fukui Y, Ikeura T, Fukui T, Nishio A, Shikata N, Uemura Y, Satoi S, Mizuno N, Notohara K, Shimosegawa T, Zamboni G, Frulloni L, Okazaki K. Comparison of neutrophil infiltration between type 1 and type 2 autoimmune pancreatitis. Pancreatology 2015; 15:271-80. [PMID: 25818196 DOI: 10.1016/j.pan.2015.03.005] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2014] [Revised: 03/02/2015] [Accepted: 03/06/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Characteristics of type 2 autoimmune pancreatitis (AIP) is granulocyte epithelial lesions, called idiopathic duct-centric pancreatitis (IDCP). To clarify pathogenesis of IDCP, we investigated mechanism of neutrophil infiltration in type 1 AIP, called lymphoplasmacytic sclerosing pancreatitis (LPSP) and IDCP. METHOD This study was performed on resected pancreata from patients with alcoholic chronic pancreatitis (ACP, n = 10), LPSP (n = 10) and IDCP (n = 12). The number of neutrophils around the pancreatic ducts was counted. The expression of neutrophils chemoattractants granulocyte chemotactic protein-2 (GCP-2) and interleukin-8 (IL-8) in the pancreatic duct epithelia was examined using immunohistochemistry. The cell staining intensity is scored as negative (0), weak (1), moderate (2) or strong (3). RESULTS The median number of neutrophils around the interlobular pancreatic ducts was significantly higher in IDCP (15.16; interquartile range [IQR]: 9.74-18.41) than in ACP (2.66; IQR: 1.33-4.33) (P < 0.05) and LPSP (3.16; IQR: 2.74-4.57) (P < 0.01). There was no significant difference in the median number of neutrophils around the intralobular pancreatic ducts among ACP (1.16; IQR: 0.33-3.41), LPSP (3.16; IQR: 0.74-5.5) and IDCP (3.00; IQR: 1.08-7.91). The median score of GCP-2 in the interlobular pancreatic duct epithelia was significantly higher in IDCP (1.5; IQR: 0.25-2) than in ACP (0; IQR: 0-0.75) (P < 0.05) and LPSP (0; IQR: 0-0.75) (P < 0.05). There was no significant difference in the median score of IL-8 in the interlobular pancreatic duct epithelia among ACP (0; IQR: 0-0.75), LPSP (1; IQR: 0-1.75) and IDCP (0.5; IQR: 0-1). CONCLUSIONS Significantly increased neutrophil infiltration around the interlobular pancreatic duct in IDCP may depend on GCP-2.
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Affiliation(s)
- Toshiyuki Mitsuyama
- Department of Gastroenterology and Hepatology, Kansai Medical University, Japan
| | - Kazushige Uchida
- Department of Gastroenterology and Hepatology, Kansai Medical University, Japan
| | - Kimi Sumimoto
- Department of Gastroenterology and Hepatology, Kansai Medical University, Japan
| | - Yuri Fukui
- Department of Gastroenterology and Hepatology, Kansai Medical University, Japan
| | - Tsukasa Ikeura
- Department of Gastroenterology and Hepatology, Kansai Medical University, Japan
| | - Toshiro Fukui
- Department of Gastroenterology and Hepatology, Kansai Medical University, Japan
| | - Akiyoshi Nishio
- Department of Gastroenterology and Hepatology, Kansai Medical University, Japan
| | | | - Yoshiko Uemura
- Department of Pathology, Kansai Medical University, Japan
| | - Sohei Satoi
- Department of Surgery, Kansai Medical University, Japan
| | - Nobumasa Mizuno
- Department of Gastroenterology, Aichi Cancer Center Hospital, Japan
| | - Kenji Notohara
- Department of Pathology, Kurashiki Central Hospital, Japan
| | - Tooru Shimosegawa
- Department of Gastroenterology, Tohoku University Graduate School of Medicine, Japan
| | | | - Luca Frulloni
- Department of Medicine, Pancreas Center, University of Verona, Italy
| | - Kazuichi Okazaki
- Department of Gastroenterology and Hepatology, Kansai Medical University, Japan.
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Kleger A, Seufferlein T, Wagner M, Tannapfel A, Hoffmann TK, Mayerle J. IgG4-related autoimmune diseases: Polymorphous presentation complicates diagnosis and treatment. DEUTSCHES ARZTEBLATT INTERNATIONAL 2015; 112:128-35. [PMID: 25759979 PMCID: PMC4361802 DOI: 10.3238/arztebl.2015.0128] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Revised: 11/11/2014] [Accepted: 11/11/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND IgG4-associated autoimmune diseases are systemic diseases affecting multiple organs of the body. Autoimmune pancreatitis, with a prevalence of 2.2 per 100,000 people, is one such disease. Because these multi-organ diseases present in highly variable ways, they were long thought just to affect individual organ systems. This only underscores the importance of familiarity with these diseases for routine clinical practice. METHODS This review is based on pertinent articles retrieved by a selective search in PubMed, and on the published conclusions of international consensus conferences. RESULTS The current scientific understanding of this group of diseases is based largely on case reports and small case series; there have not been any randomized controlled trials (RCTs) to date. Any organ system can be affected, including (for example) the biliary pathways, salivary glands, kidneys, lymph nodes, thyroid gland, and blood vessels. Macroscopically, these diseases cause diffuse organ swelling and the formation of pseudotumorous masses. Histopathologically, they are characterized by a lymphoplasmacytic infiltrate with IgG4-positive plasma cells, which leads via an autoimmune mechanism to the typical histologic findings--storiform fibrosis ("storiform" = whorled, like a straw mat) and obliterative, i.e., vessel-occluding, phlebitis. A mixed Th1 and Th2 immune response seems to play an important role in pathogenesis, while the role of IgG4 antibodies, which are not pathogenic in themselves, is still unclear. Glucocorticoid treatment leads to remission in 98% of cases and is usually continued for 12 months as maintenance therapy. Most patients undergo remission even if untreated. Steroid-resistant disease can be treated with immune modulators. CONCLUSION IgG4-associated autoimmune diseases are becoming more common, but adequate, systematically obtained data are now available only from certain Asian countries. Interdisciplinary collaboration is a prerequisite to proper diagnosis and treatment. Treatment algorithms and RCTs are needed to point the way to organ-specific treatment in the future.
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Affiliation(s)
- Alexander Kleger
- Ulm University Medical Center, Department of Internal Medicine I
| | | | - Martin Wagner
- Ulm University Medical Center, Department of Internal Medicine I
| | | | - Thomas K Hoffmann
- Department of Oto-Rhino-Laryngology Head and Neck Surgery, Ulm University Medical Center
| | - Julia Mayerle
- University Medicine Greifswald Department of Internal Medicine A
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Joshi D, Webster GJM. Biliary and hepatic involvement in IgG4-related disease. Aliment Pharmacol Ther 2014; 40:1251-61. [PMID: 25312536 DOI: 10.1111/apt.12988] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2014] [Revised: 07/30/2014] [Accepted: 09/24/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND IgG4-related disease (IgG4-RD) is a multi-systemic disorder. IgG4-related sclerosing cholangitis (IgG4-SC) is the biliary manifestation of the disease, often in association with autoimmune pancreatitis (AIP). Hepatic manifestations of IgG4-RD are less well described within the literature. AIM To examine and present an overview of IgG4-RD with a focus on the biliary and hepatic manifestations. METHODS An electronic search using Medline was performed. Search items included 'IgG4 multi-system disease, IgG4 associated cholangitis, IgG4 associated liver disease and autoimmune pancreatitis (AIP)'. RESULTS IgG4-RD is characterised by an IgG4-positive lymphoplasmacytic tissue infiltrate, storiform fibrosis and an obliterative phlebitis. The HISORt criteria may be used to establish the diagnosis and incorporate a multi-disciplinary approach involving histology, radiology, serum IgG4 levels and response to steroid therapy. IgG4-SC is the commonest extrapancreatic manifestation of type-1 AIP, while the hepatic manifestations remain poorly defined. Important differential diagnoses include primary sclerosing cholangitis, secondary sclerosing cholangitis, cholangiocarcinoma and pancreatic carcinoma. Current treatment regimens remain ill defined although steroid therapy is used first line unless contraindicated. Patients with relapsing disease or multifocal disease should be considered for azathioprine. Available data would also suggest a role for rituximab. CONCLUSIONS IgG4-related sclerosing cholangitis is a common manifestation of IgG4-related disease which requires a multi-disciplinary approach to establish the diagnosis. Differentiating IgG4-related sclerosing cholangitis from other conditions, both benign and malignant, is challenging, but vital. Steroids remain the mainstay of treatment. Our understanding of the pathogenesis of the hepatic manifestations of IgG4-related disease continues to evolve.
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Affiliation(s)
- D Joshi
- Department of Gastroenterology, University College Hospital, London, UK
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Bulajic M, Panic N, Löhr JM. Helicobacter pylori and pancreatic diseases. World J Gastrointest Pathophysiol 2014; 5:380-383. [PMID: 25400980 PMCID: PMC4231501 DOI: 10.4291/wjgp.v5.i4.380] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2014] [Revised: 04/14/2014] [Accepted: 07/17/2014] [Indexed: 02/06/2023] Open
Abstract
A possible role for Helicobacter pylori (H. pylori) infection in pancreatic diseases remains controversial. H. pylori infection with antral predomination leading to an increase in pancreatic bicarbonate output and inducing ductal epithelial cell proliferation could contribute to the development of pancreatic cancer via complex interactions with the ABO genotype, dietary and smoking habits and N-nitrosamine exposure of the host. Although the individual study data available so far is inconsistent, several meta-analyses have reported an increased risk for pancreatic cancer among H. pylori seropositive individuals. It has been suggested that H. pylori causes autoimmune pancreatitis due to molecular mimicry between H. pyloriα-carbonic anhydrase (α-CA) and human CA type II, and between H. pylori plasminogen-binding protein and human ubiquitin-protein ligase E3 component n-recognin 2, enzymes that are highly expressed in the pancreatic ductal and acinar cells, respectively. Future studies involving large numbers of cases are needed in order to examine the role of H. pylori in autoimmune pancreatitis more fully. Considering the worldwide pancreatic cancer burden, as well as the association between autoimmune pancreatitis and other autoimmune conditions, a complete elucidation of the role played by H. pylori in the genesis of such conditions could have a substantial impact on healthcare.
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POLYZOS SA, NIKOLOPOULOS P, STOGIANNI A, ROMIOPOULOS I, KATSINELOS P, KOUNTOURAS J. EFFECT OF HELICOBACTER PYLORI ERADICATION ON HEPATIC STEATOSIS, NAFLD FIBROSIS SCORE AND HSENSI IN PATIENTS WITH NONALCOHOLIC STEATOHEPATITIS: a MR imaging-based pilot open-label study. ARQUIVOS DE GASTROENTEROLOGIA 2014; 51:261-8. [DOI: 10.1590/s0004-28032014000300017] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/03/2014] [Accepted: 04/30/2014] [Indexed: 12/15/2022]
Abstract
Context Limited clinical data suggest Helicobacter pylori (Hp) infection may contribute to nonalcoholic fatty liver disease (NAFLD) pathogenesis. Objectives The effect of Hp eradication on hepatic steatosis (magnetic resonance imaging), nonalcoholic fatty liver disease fibrosis score and HSENSI (Homocysteine, serum glutamic oxaloacetic transaminase, Erythrocyte sedimentation rate, nonalcoholic steatohepatitis Index) in nonalcoholic steatohepatitis patients. Methods Thirteen adult patients with biopsy-proven nonalcoholic steatohepatitis, asymptomatic for gastrointestinal disease, underwent 13C urea breath test; Hp positive patients received eradication therapy until repeat test become negative. Hepatic fat fraction, standard biochemical tests and calculation of nonalcoholic fatty liver disease fibrosis score and HSENSI were performed at baseline and month 12. Results Hepatic fat fraction was similar for between and within group comparisons. Nonalcoholic fatty liver disease fibrosis score showed a non-significant trend towards decrease in Hp(+) [-0.34 (-1.39-0.29) at baseline and -0.24 (-0.99-0.71) at month 12; P = 0.116], whereas increase in Hp(-) group [-0.38 (-1.72-0.11) and -0.56 (-1.43-0.46), respectively; P = 0.249]. HSENSI was significantly decreased only in Hp(+) group [1.0 (1.0-2.0) at baseline and 1.0 (0-1.0) at month 12; P = 0.048]. Conclusions Hp eradication had no long-term effect on hepatic steatosis, but showed a trend towards improvement in nonalcoholic fatty liver disease fibrosis score and HSENSI. These results warrant larger studies with paired biopsies.
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Okazaki K, Yanagawa M, Mitsuyama T, Uchida K. Recent advances in the concept and pathogenesis of IgG4-related disease in the hepato-bilio-pancreatic system. Gut Liver 2014; 8:462-70. [PMID: 25228969 PMCID: PMC4164252 DOI: 10.5009/gnl14107] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2014] [Accepted: 04/15/2014] [Indexed: 12/24/2022] Open
Abstract
Recent studies have proposed nomenclatures of type 1 autoimmune pancreatitis (AIP) (IgG4-related pancreatitis), IgG4-related sclerosing cholangitis (IgG4-SC), IgG4-related cholecystitis, and IgG4-related hepatopathy as IgG4-related disease (IgG4-RD) in the hepato-bilio-pancreatic system. In IgG4-related hepatopathy, a novel concept of IgG4-related autoimmune hepatitis (AIH) with the same histopathological features as AIH has been proposed. Among organs involved in IgG4-RD, associations with pancreatic and biliary lesions are most frequently observed, supporting the novel concept of “biliary diseases with pancreatic counterparts.” Targets of type 1 AIP and IgG4-SC may be periductal glands around the bile and pancreatic ducts. Based on genetic backgrounds, innate and acquired immunity, Th2-dominant immune status, regulatory T (Treg) or B cells, and complement activation via a classical pathway may be involved in the development of IgG4-RD. Although the role of IgG4 remains unclear in IgG4-RD, IgG4-production is upregulated by interleukin 10 from Treg cells and by B cell activating factor from monocytes/basophils with stimulation of toll-like receptors/nucleotide-binding oligomerization domain-like receptors. Based on these findings, we have proposed a hypothesis for the development of IgG4-RD in the hepato-bilio-pancreatic system. Further studies are necessary to clarify the pathogenic mechanism of IgG4-RD.
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Affiliation(s)
- Kazuichi Okazaki
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Masahito Yanagawa
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Toshiyuki Mitsuyama
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
| | - Kazushige Uchida
- Division of Gastroenterology and Hepatology, The Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan
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Hubers LM, Maillette de Buy Wenniger LJ, Doorenspleet ME, Klarenbeek PL, Verheij J, Rauws EA, van Gulik TM, Oude Elferink RPJ, van de Graaf SFJ, de Vries N, Beuers U. IgG4-Associated Cholangitis: A Comprehensive Review. Clin Rev Allergy Immunol 2014; 48:198-206. [PMID: 24958363 DOI: 10.1007/s12016-014-8430-2] [Citation(s) in RCA: 49] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Lowiek M Hubers
- Department of Gastroenterology and Hepatology and Tytgat Institute of Liver and Intestinal Research, Academic Medical Center, University of Amsterdam, Meibergdreef 9, room G4-216, 1105 AZ, Amsterdam, The Netherlands
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Okazaki K, Uchida K, Sumimoto K, Mitsuyama T, Ikeura T, Takaoka M. Autoimmune pancreatitis: pathogenesis, latest developments and clinical guidance. Ther Adv Chronic Dis 2014; 5:104-11. [PMID: 24790726 DOI: 10.1177/2040622314527120] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Recently, autoimmune pancreatitis has been classified into two subtypes. Type 1 is related to immunoglobulin G4 and type 2 is related to granulocytic epithelial lesions, but pathogenetic mechanisms in both still remain unclear. Apart from type 2 autoimmune pancreatitis, the pathological features of type 1 autoimmune pancreatitis with increased serum immunoglobulin G4/immunoglobulin E levels, abundant infiltration of immunoglobulin G4+plasmacytes and lymphocytes, fibrosis, and steroid responsiveness are suggestive of abnormal immunity such as allergy or autoimmunity. Although pathophysiological conditions seem to be different in each, both respond well to steroid drugs. After remission, the patients with type 1 autoimmune pancreatitis show high relapse rates (30-50% within 6-12 months), whereas those with type 2 autoimmune pancreatitis seldom relapse. After remission, the steroid maintenance therapy and therapeutic strategy for relapsing patients with type 1 is different among local expertise. In this paper, recent advances in pathogenesis and clinical guidance for therapy are discussed.
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Affiliation(s)
- Kazuichi Okazaki
- Third Department of Internal Medicine, Division of Gastroenterology and Hepatology, Kansai Medical University, Shinmachi, Hirakata, Osaka 573-1197, Japan
| | - Kazushige Uchida
- Department of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan
| | - Kimi Sumimoto
- Department of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan
| | - Toshiyuki Mitsuyama
- Department of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan
| | - Tsukasa Ikeura
- Department of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan
| | - Makoto Takaoka
- Department of Gastroenterology and Hepatology, Kansai Medical University, Osaka, Japan
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Immunoglobulin G4-related pancreatic and biliary diseases. CANADIAN JOURNAL OF GASTROENTEROLOGY = JOURNAL CANADIEN DE GASTROENTEROLOGIE 2014; 27:523-30. [PMID: 24078937 DOI: 10.1155/2013/180461] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND Autoimmune pancreatitis and autoimmune cholangitis are new clinical entities that are now recognized as the pancreatico-biliary manifestations of immunoglobulin (Ig) G4-related disease. OBJECTIVE To summarize important clinical aspects of IgG4-related pancreatic and biliary diseases, and to review the role of IgG4 in the diagnosis of autoimmune pancreatitis (AIP) and autoimmune cholangitis (AIC). METHODS A narrative review was performed using the PubMed database and the following keywords: "IgG4", "IgG4 related disease", "autoimmune pancreatitis", "sclerosing cholangitis" and "autoimmune cholangitis". A total of 955 articles were retrieved; of these, 381 contained relevant data regarding the IgG4 molecule, pathogenesis of IgG-related diseases, and diagnosis, management and long-term follow-up for patients with AIP and AIC. Of these 381 articles, 66 of the most pertinent were selected. RESULTS The selected studies demonstrated the increasing clinical importance of both AIP and AIC, which can mimic pancreatic cancer and cholangiocarcinoma, respectively. IgG4 titration in tissue or blood cannot be used alone to diagnose all IgG4-related diseases; however, it is often a useful adjunct to clinical, radiological and histological features. AIP and AIC respond to steroids; however, relapse is common and long-term maintenance treatment often required. CONCLUSIONS A review of the diagnosis and management of both AIC and AIP is timely and pertinent to clinical practice because the amount of information regarding these conditions has increased substantially in the past few years, resulting in significant impact on the clinical management of affected patients.
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Kountouras J, Zavos C, Polyzos SA, Michael S, Tsiaousi E, Vardaka E, Katsinelos P, Kouklakis G, Paikos D, Gavalas E, Deretzi G, Giartza-Taxidou E, Loli E. Relationship between Helicobacter pylori infection and autoimmune disorders. Clin Chem Lab Med 2014; 51:e73-4. [PMID: 23314537 DOI: 10.1515/cclm-2012-0753] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2012] [Accepted: 11/18/2012] [Indexed: 11/15/2022]
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Abstract
The discovery of Helicobacter pylori infection in the stomach could be considered as one of the most important events of modern gastroenterology. Understanding of the natural history of many disorders of the upper gastrointestinal tract, including chronic gastritis, peptic ulcer disease, gastric cancer and MALT lymphoma, was altered by this discovery. Interestingly, epidemiological studies have also revealed a correlation between H. pylori infection and some diseases localized outside the stomach, especially those characterized by persistent and low-grade systemic inflammation. Of note, H. pylori has an important role in iron deficiency anaemia, idiopathic thrombocytopenic purpura and vitamin B12 deficiency. Moreover, the association of this bacterial pathogen with many other diseases, including hepatobiliary, pancreatic, cardiovascular and neurodegenerative disorders is currently under investigation. In this Review, we summarize the results of the most important studies performed to date surrounding the association of H. pylori infection with extragastric diseases, as well as the strength of the evidence. We also provide information concerning bacterial-host interactions and the mechanisms implicated in the pathogenesis of each of these extragastric diseases.
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Mahajan VS, Mattoo H, Deshpande V, Pillai SS, Stone JH. IgG4-related disease. ANNUAL REVIEW OF PATHOLOGY 2014; 9:315-47. [PMID: 24111912 DOI: 10.1146/annurev-pathol-012513-104708] [Citation(s) in RCA: 248] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated condition that can affect almost any organ and is now being recognized with increasing frequency. IgG4-RD is characterized by a lymphoplasmacytic infiltrate composed of IgG4(+) plasma cells, storiform fibrosis, obliterative phlebitis, and mild to moderate eosinophilia. The diagnosis of IgG4-RD unifies many eponymous fibroinflammatory conditions that had previously been thought to be confined to single organs. IgG4-RD lesions are infiltrated by T helper cells, which likely cause progressive fibrosis and organ damage. IgG4 antibodies are generally regarded as noninflammatory. Although autoreactive IgG4 antibodies are observed in IgG4-RD, there is no evidence that they are directly pathogenic. Rituximab-induced B cell depletion in IgG4-RD leads to rapid clinical and histological improvement accompanied by swift declines in serum IgG4 concentrations. Although IgG autoantibodies against various exocrine gland antigens have been described in IgG4-RD, whether they are members of the IgG4 subclass is unknown. The contribution of autoantibodies to IgG4-RD remains unclear.
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Zhao JB, Liao DH, Nissen TD. Animal models of pancreatitis: Can it be translated to human pain study? World J Gastroenterol 2013; 19:7222-7230. [PMID: 24259952 PMCID: PMC3831203 DOI: 10.3748/wjg.v19.i42.7222] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2013] [Revised: 08/12/2013] [Accepted: 08/20/2013] [Indexed: 02/06/2023] Open
Abstract
Chronic pancreatitis affects many individuals around the world, and the study of the underlying mechanisms leading to better treatment possibilities are important tasks. Therefore, animal models are needed to illustrate the basic study of pancreatitis. Recently, animal models of acute and chronic pancreatitis have been thoroughly reviewed, but few reviews address the important aspect on the translation of animal studies to human studies. It is well known that pancreatitis is associated with epigastric pain, but the understanding regarding to mechanisms and appropriate treatment of this pain is still unclear. Using animal models to study pancreatitis associated visceral pain is difficult, however, these types of models are a unique way to reveal the mechanisms behind pancreatitis associated visceral pain. In this review, the animal models of acute, chronic and un-common pancreatitis are briefly outlined and animal models related to pancreatitis associated visceral pain are also addressed.
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A case of Epstein-Barr virus-related lymphadenopathy mimicking the clinical features of IgG4-related disease. Mod Rheumatol 2012; 23:597-603. [PMID: 22842848 DOI: 10.1007/s10165-012-0695-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2012] [Accepted: 05/30/2012] [Indexed: 10/28/2022]
Abstract
We report an intriguing case of Epstein-Barr virus (EBV)-related multiple lymphadenopathy that clinically mimics immunoglobulin G4-related disease (IgG4-RD). A 72-year-old woman presented with a history of asthma attacks, systemic lymphadenopathy, hypergammaglobulinemia, proteinuria, and an elevated level of serum IgG4, leading to a possible diagnosis of IgG4-RD based on current comprehensive diagnostic criteria. However, a percutaneous kidney biopsy specimen showed mild mesangial proliferative glomerulonephritis with focal membranous transformation, and there was no interstitial lesion or lymphocyte infiltration. Cervical lymph node biopsy demonstrated follicular hyperplasia associated with prominent lymphoplasmacytic infiltration in the interfollicular area. However, only a few IgG4-positive plasma cells were present. An in situ hybridization study demonstrated many EBV-infected lymphocytes in the germinal center as well as in the interfollicular area. This case illustrates the diversity of conditions associated with elevated levels of serum IgG4 and the necessity for tissue biopsy when diagnosing IgG4-RD.
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Helicobacter pylori and autoimmune diseases. Biomed Pharmacother 2012; 67:347-9. [PMID: 23583190 DOI: 10.1016/j.biopha.2011.09.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2011] [Accepted: 09/06/2011] [Indexed: 12/20/2022] Open
Abstract
It is now widely accepted that Helicobacter pylori may play a role in several extra-gastric diseases. In particular, H. pylori infection seems to be implicated in various autoimmune diseases. Many recent studies have shown a healing or an improvement in different autoimmune disorders after H. pylori eradication therapy in infected patients. The exact mechanisms behind this relationship remain under discussion, but molecular mimicry is a consistent hypothesis. This subject is particularly relevant taking into consideration the high prevalence of H. pylori infection, the existence of inexpensive and noninvasive diagnostic methods, as the urea breath test or the stool antigen test, and the low cost and toxicity of eradication treatment. If this connection becomes confirmed, it can change the diagnostic and therapeutic approach of some autoimmune diseases.
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Farrell JJ, Zhang L, Zhou H, Chia D, Elashoff D, Akin D, Paster BJ, Joshipura K, Wong DTW. Variations of oral microbiota are associated with pancreatic diseases including pancreatic cancer. Gut 2012; 61:582-8. [PMID: 21994333 PMCID: PMC3705763 DOI: 10.1136/gutjnl-2011-300784] [Citation(s) in RCA: 470] [Impact Index Per Article: 36.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE The associations between oral diseases and increased risk of pancreatic cancer have been reported in several prospective cohort studies. In this study, we measured variations of salivary microbiota and evaluated their potential associations with pancreatic cancer and chronic pancreatitis. METHODS This study was divided into three phases: (1) microbial profiling using the Human Oral Microbe Identification Microarray to investigate salivary microbiota variation between 10 resectable patients with pancreatic cancer and 10 matched healthy controls, (2) identification and verification of bacterial candidates by real-time quantitative PCR (qPCR) and (3) validation of bacterial candidates by qPCR on an independent cohort of 28 resectable pancreatic cancer, 28 matched healthy control and 27 chronic pancreatitis samples. RESULTS Comprehensive comparison of the salivary microbiota between patients with pancreatic cancer and healthy control subjects revealed a significant variation of salivary microflora. Thirty-one bacterial species/clusters were increased in the saliva of patients with pancreatic cancer (n=10) in comparison to those of the healthy controls (n=10), whereas 25 bacterial species/clusters were decreased. Two out of six bacterial candidates (Neisseria elongata and Streptococcus mitis) were validated using the independent samples, showing significant variation (p<0.05, qPCR) between patients with pancreatic cancer and controls (n=56). Additionally, two bacteria (Granulicatella adiacens and S mitis) showed significant variation (p<0.05, qPCR) between chronic pancreatitis samples and controls (n=55). The combination of two bacterial biomarkers (N elongata and S mitis) yielded a receiver operating characteristic plot area under the curve value of 0.90 (95% CI 0.78 to 0.96, p<0.0001) with a 96.4% sensitivity and 82.1% specificity in distinguishing patients with pancreatic cancer from healthy subjects. CONCLUSIONS The authors observed associations between variations of patients' salivary microbiota with pancreatic cancer and chronic pancreatitis. This report also provides proof of salivary microbiota as an informative source for discovering non-invasive biomarkers of systemic diseases.
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Affiliation(s)
- James J Farrell
- Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
| | - Lei Zhang
- UCLA School of Dentistry, Dental Research Institute, Los Angeles, California, USA
| | - Hui Zhou
- UCLA School of Dentistry, Dental Research Institute, Los Angeles, California, USA
| | - David Chia
- Department of Pathology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
| | - David Elashoff
- Department of Biostatistics, UCLA School of Public Health, Los Angeles, California, USA
| | - David Akin
- UCLA School of Dentistry, Dental Research Institute, Los Angeles, California, USA
| | - Bruce J Paster
- Department of Molecular Genetics, The Forsyth Institute, Boston, Massachusetts, USA
| | - Kaumudi Joshipura
- University of Puerto Rico, School of Dental Medicine, San Juan, Puerto Rico
| | - David T W Wong
- UCLA School of Dentistry, Dental Research Institute, Los Angeles, California, USA
,Jonsson Comprehensive Cancer Center, Los Angeles, California, USA
,Division of Head and Neck Surgery/Otolaryngology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
,Henry Samueli School of Engineering and Applied Science, David Geffen School of Medicine at UCLA, Los Angeles, California, USA
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Abstract
• AIP is a heterogeneous disease with two distinct subtypes, now called type 1 and type 2. The proportions of these subtypes vary in their distribution worldwide. • Pancreatic cancer is the leading differential diagnosis for AIP, although AIP can mimic any other major pancreatobiliary disease. • Cross-sectional abdominal imaging CT/MRI should form the cornerstone to the diagnosis of AIP. • Serum IgG4 provides collateral evidence for the diagnosis of AIP and should not be the sole basis for the diagnosis. False-positive elevation in serum IgG4 can be seen in up to 10% of patients with pancreatic cancer. • A steroid trial should be performed only in select situations after ruling out pancreatic cancer and by gastroenterologists experienced in treating AIP. • Disease recurrence can be seen in up to 40% of patients after initial steroid therapy.
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Updated assessment of the prevalence, spectrum and case definition of autoimmune disease. Autoimmun Rev 2012; 11:754-65. [PMID: 22387972 DOI: 10.1016/j.autrev.2012.02.001] [Citation(s) in RCA: 313] [Impact Index Per Article: 24.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2012] [Accepted: 01/31/2012] [Indexed: 12/13/2022]
Abstract
Autoimmune diseases are heterogeneous with regard to prevalence, manifestations, and pathogenesis. The classification of autoimmune diseases has varied over time. Here, we have compiled a comprehensive up-to-date list of the autoimmune diseases, and have reviewed published literature to estimate their prevalence. We identified 81 autoimmune diseases. The overall estimated prevalence is 4.5%, with 2.7% for males and 6.4% for females. For specific diseases, prevalence ranges from 1% to <1/10(6). Considering all diseases in the class, the most common mean age-of-onset was 40-50 years. This list of autoimmune diseases has also yielded information about autoantigens. Forty-five autoimmune diseases have been associated with well-defined autoantigens. Of the diseases with known autoantigens, 33.3% had highly repetitive sequences, 35.6% had coiled-coil arrangements and 57.8% were associated with cellular membranes, which means that based on these structural motifs alone, autoantigens do not appear to be a random sample of the human proteome. Finally, we identified 19 autoimmune diseases that phenocopy diseases arising from germline mutations in the corresponding autoantigen. Collectively, our findings lead to a tentative proposal for criteria for assigning autoimmune pathogenesis to a particular disease.
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Abstract
Recent studies suggested the existence of two subtypes of autoimmune pancreatitis (AIP): type 1 related with IgG4 (lymphoplasmacytic sclerosing pancreatitis; LPSP) and type 2 related with a granulocytic epithelial lesion (idiopathic duct-centric chronic pancreatitis; IDCP). Apart from type 2 AIP, the pathological features of type 1 AIP with increased serum IgG4/IgE levels, abundant infiltration of IgG4+ plasmacytes and lymphocytes, fibrosis, and steroid responsiveness are suggestive of abnormal immunity such as allergy or autoimmunity. Moreover, the patients with type 1 AIP often have extrapancreatic lesions such as sclerosing cholangitis, sclerosing sialadenitis, or retroperitoneal fibrosis showing similar pathological features. Based on these findings, many synonyms have been proposed for these conditions, such as "multifocal idiopathic fibrosclerosis", "IgG4-related autoimmune disease", "IgG4-related sclerosing disease", "IgG4-related plasmacytic disease", and "IgG4-related multiorgan lymphoproliferative syndrome", all of which may refer to the same conditions. Therefore, the Japanese Research Committee for "Systemic IgG4-related Sclerosing Disease" proposed a disease concept and clinical diagnostic criteria based on the concept of multifocal fibrosclerosis in 2009, in which the term "IgG4-related disease" was appointed as a minimal consensus on these conditions. Although the significance of IgG4 in the development of "IgG4-related disease" remains unclear, we have proposed a hypothesis for the development of type 1 AIP, one of the IgG4-related disease. The concept and diagnostic criteria of "IgG4-related disease" will be changed in accordance with future studies.
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Abstract
Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recently defined emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. IgG4-RSD usually affects middle aged and elderly patients, with a male predominance. It is associated with an elevated serum titer of IgG4, which acts as a marker for this recently characterized entity. The prototype is IgG4-related sclerosing pancreatitis or autoimmune pancreatitis (AIP). Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, however practically any organ can be involved, including upper aerodigestive tract, lung, aorta, mediastinum, retroperitoneum, soft tissue, skin, central nervous system, breast, kidney, and prostate. Fever or constitutional symptoms usually do not comprise part of the clinical picture. Laboratory findings detected include raised serum globulin, IgG and IgG4. An association with autoantibody detection (such as antinuclear antibodies and rheumatoid factor) is seen in some cases. Steroid therapy comprises the mainstay of treatment. Disease progression with involvement of multiple organ-sites may be encountered in a subset of cases and may follow a relapsing-remitting course. The principal histopathologic findings in several extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, along with atrophy and destruction of tissues. Immunohistochemical staining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). IgG4-RSD may potentially be rarely associated with the development of lymphoma and carcinoma. However, the nature and pathogenesis of IgG4-RSD are yet to be fully elucidated and provide immense scope for further studies.
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Affiliation(s)
- Mukul Divatia
- Department of Pathology, The Methodist Hospital, Weill Medical College of Cornell University, Houston, TX, USA
| | - Sun A Kim
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jae Y. Ro
- Department of Pathology, The Methodist Hospital, Weill Medical College of Cornell University, Houston, TX, USA
- Department of Pathology, Yonsei University College of Medicine, Seoul, Korea
- National Cancer Center, Goyang, Korea
- The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
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Campuzano-Maya G. Cure of alopecia areata after eradication of Helicobacter pylori: a new association? World J Gastroenterol 2011; 17:3165-70. [PMID: 21912461 PMCID: PMC3158418 DOI: 10.3748/wjg.v17.i26.3165] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2011] [Revised: 03/05/2011] [Accepted: 03/12/2011] [Indexed: 02/06/2023] Open
Abstract
Alopecia areata is a disease of the hair follicles, with strong evidence supporting autoimmune etiology. Alopecia areata is frequently associated with immune-mediated diseases with skin manifestations such as psoriasis and lichen planus, or without skin manifestations such as autoimmune thyroiditis and idiopathic thrombocytopenic purpura. Helicobacter pylori (H. pylori) infection is present in around 50% of the world's population and has been associated with a variety of immune-mediated extra-digestive disorders including autoimmune thyroiditis, idiopathic thrombocytopenic purpura, and psoriasis. A case of a 43-year old man with an 8-mo history of alopecia areata of the scalp and beard is presented. The patient was being treated by a dermatologist and had psychiatric support, without any improvement. He had a history of dyspepsia and the urea breath test confirmed H. pylori infection. The patient went into remission from alopecia areata after H. pylori eradication. If such an association is confirmed by epidemiological studies designed for this purpose, new therapeutic options could be available for these patients, especially in areas where infection with H. pylori is highly prevalent.
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Normalización de enzimas pancreáticas tras erradicación de Helicobacter pylori en un paciente de 7 años. An Pediatr (Barc) 2011; 75:77-8. [DOI: 10.1016/j.anpedi.2011.02.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2010] [Revised: 02/16/2011] [Accepted: 02/17/2011] [Indexed: 11/19/2022] Open
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Abstract
PURPOSE OF REVIEW IgG4-related systemic disease (ISD) is a recently recognized syndrome affecting multiple organs. Autoimmune pancreatitis (AIP) is the pancreatic manifestation of ISD and mimics pancreatic cancer. Current data show frequent association with serum IgG4 elevation and other serologic abnormalities. Here we explore the diagnostic and possible prognostic utility and pathogenetic implications of serologic abnormalities in ISD. RECENT FINDINGS Serum IgG4 elevations (>140 mg/dl) are seen in 70-80% of AIP patients and also in 5% of normal population and 10% of pancreatic cancer making it an unsuitable single marker for diagnosis. However, when combined with other features of AIP, it can be of great diagnostic value though its utility in monitoring of therapy or as a marker or predictor of relapse is limited. Several other antibodies have been identified in AIP against pancreas-specific antigens like trypsinogens I and II, pancreatic secretory trypsin inhibitor (PSTI) and plasminogen binding protein (PBP) and other nonpancreas-specific antigens. Anti-PBP antibodies appear to have potential diagnostic utility but require further validation. SUMMARY No single serologic marker is diagnostic of ISD. Serum IgG4 elevation has convincing diagnostic utility when combined with other disease features although its value in disease monitoring may be limited.
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