|
1
|
Ma XY, Hao Y, Xie YH, Cao Q, Sun DF, Wang JL, Zhang YX, Cui Y, Zhang Y, Ding H, Sun TT, Tan J, Fu LN, Zou TH, Yu QX, Yu YN, Wu Q, Yang L, Zhang MX, Aiken A, Shu X, Sheng JQ, Wang YG, Tian ZB, Wang BM, Zhou CB, Chen YX, Fang JY. Risk Factors Analysis and Predictive Model Construction for Autoimmune Gastritis: A Nationwide Multicenter Case-Control Study in China. J Gastroenterol Hepatol 2025; 40:1202-1212. [PMID: 40040604 DOI: 10.1111/jgh.16912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 01/13/2025] [Accepted: 02/14/2025] [Indexed: 03/06/2025]
Abstract
OBJECTIVE Here, we ascertained the clinical characteristics of Chinese patients with autoimmune gastritis (AIG) and determined the correlation of dietary and lifestyle factors with AIG occurrence and development to establish a noninvasive predictive model for AIG. METHODS In this case-control study, we enrolled 479 patients from seven independent centers nationwide in China; of them, 279 had AIG, 112 had chronic atrophic gastritis mostly in the antrum, and 88 had chronic nonatrophic gastritis. Their clinical and lifestyle data were systematically collected and analyzed. Finally, a multivariate logistic regression disease prediction model was then established and validated. RESULTS Most of the 279 patients with AIG were middle-aged, older, and female. In the predictive model of AIG, the larger amount of cooking oil used per meal and comorbid autoimmune thyroid disease was considered risk factors, and a diet rich in vitamin B12 was considered a protective factor. We plotted a receiver operating characteristic (ROC) curve of the model in the discovery and validation cohorts, and the areas under the ROC curves were 0.72 and 0.74, respectively. In addition, dietary structure, eating habits, sleep quality, and smoking status were noted to be correlated with the occurrence of gastrointestinal symptoms and complications, as well as histopathological grades of AIG. CONCLUSION Dietary and lifestyle factors may predict AIG risk in Chinese populations and were related to AIG prognosis.
Collapse
Affiliation(s)
- Xin-Yue Ma
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yu Hao
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yuan-Hong Xie
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Qin Cao
- Health Management Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Dan-Feng Sun
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ji-Lin Wang
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Department of Gastroenterology, Kashgar Prefecture Second People's Hospital, Kashgar, Xinjiang Uygur Autonomous Region, China
| | - Ya-Xuan Zhang
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yun Cui
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yao Zhang
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Hui Ding
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Tian-Tian Sun
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Juan Tan
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Lin-Na Fu
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Tian-Hui Zou
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Qing-Xiang Yu
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Disease, Tianjin Key Laboratory of Digestive Diseases, Tianjin Medical University General Hospital, Tianjin, China
| | - Ya-Nan Yu
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Qiong Wu
- Department of Gastroenterology, Shanghai Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Lang Yang
- Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital; Senior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Mei-Xia Zhang
- Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Aikepaer Aiken
- Department of Gastroenterology, Kashgar Prefecture Second People's Hospital, Kashgar, Xinjiang Uygur Autonomous Region, China
| | - Xu Shu
- Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Jian-Qiu Sheng
- Department of Gastroenterology, The Seventh Medical Center of Chinese PLA General Hospital; Senior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yu-Gang Wang
- Department of Gastroenterology, Shanghai Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zi-Bin Tian
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Bang-Mao Wang
- Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Disease, Tianjin Key Laboratory of Digestive Diseases, Tianjin Medical University General Hospital, Tianjin, China
| | - Cheng-Bei Zhou
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ying-Xuan Chen
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jing-Yuan Fang
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| |
Collapse
|
|
2
|
Chen F, Gonzalez RS. Evaluation of enterochromaffin-like cell hyperplasia can help categorize patients with Helicobacter-negative atrophic gastritis. Am J Clin Pathol 2025; 163:601-609. [PMID: 39724194 DOI: 10.1093/ajcp/aqae159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Accepted: 12/19/2024] [Indexed: 12/28/2024] Open
Abstract
OBJECTIVES Atrophic gastritis (AG) is characterized by atrophy of gastric glands-in particular, oxyntic glands-in the setting of chronic inflammation; it is often autoimmune. The diagnosis is confirmed by immunohistochemistry (IHC) for gastrin (to confirm biopsy site), and pathologists often use IHC for neuroendocrine markers to evaluate for enterochromaffin-like cell hyperplasia (ECL-H). The utility of neuroendocrine staining is unclear, and we undertook this study to determine whether ECL pattern provided any additional information in cases of Helicobacter-negative AG. METHODS We reviewed clinicopathologic findings in 184 cases from 184 patients with histologic AG and no evidence of Helicobacter infection. Using neuroendocrine IHC markers, cases were divided into 3 groups: Group 1 showed complete ECL-H (both qualitative and quantitative criteria met), group 2 showed focal ECL-H (qualitative but not quantitative criteria met), and group 3 showed no ECL-H (neither criteria met). RESULTS Group 1 patients were more likely to have positive autoantibody serologies (73%, P = .0007 vs group 2) and higher mean gastrin levels (700 pg/mL, P = .017 vs group 3), and only these patients developed gastric neuroendocrine tumors. Group 2 patients were more likely to take proton pump inhibitors (64%, P = .0002 vs group 1). Group 3 patients were more likely to be male (70%, P = .008 vs group 1) and to have microcytic anemia (44%, P = .022 vs group 2) and less likely to have intestinal metaplasia (50%, P = .044 vs group 1). CONCLUSIONS Stratification based on degree of ECL-H is not necessary for diagnosis of AG but does lead to statistically significant clinical and pathologic differences among groups.
Collapse
Affiliation(s)
- Feidi Chen
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, US
| | - Raul S Gonzalez
- Department of Pathology and Laboratory Medicine, Emory University Hospital, Atlanta, GA, US
| |
Collapse
|
|
3
|
Kishikawa H, Nishida J. Gastric cancer in patients with Helicobacter pylori-negative autoimmune gastritis. World J Gastrointest Oncol 2025; 17:101661. [PMID: 40235879 PMCID: PMC11995347 DOI: 10.4251/wjgo.v17.i4.101661] [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] [Received: 09/23/2024] [Revised: 01/06/2025] [Accepted: 01/20/2025] [Indexed: 03/25/2025] Open
Abstract
Although Helicobacter pylori (H. pylori) is implicated in the development of most cases of gastric cancer with autoimmune gastritis, cases of gastric cancer have been reported in patients testing negative for H. pylori. Here, we aimed to outline the current research status of the factors involved in the development of gastric cancer in H. pylori-negative autoimmune gastritis. Predictive pathological conditions for the development of gastric cancer in H. pylori-negative autoimmune gastritis are postulated to be: (1) Severe atrophy; (2) Hypergastrinemia; (3) Bile reflux; and (4) Low acidity, which are directly related to the pathophysiology of autoimmune gastritis, as well as smoking and family history, which are not related to autoimmune gastritis. In autoimmune gastritis, where there is a possibility of spontaneous disappearance of H. pylori in advanced atrophy, it is difficult to assess H. pylori. Since H. pylori infection begins in the antrum and subsequently progresses to the proximal stomach, it is interpreted as H. pylori-negative autoimmune gastritis if histologically consistent with autoimmune gastritis in the body with spared antrum, and negative for other H. pylori tests. However, it is essential to examine whether the currently prevailing histological interpretation used to evaluate H. pylori infection status is appropriate.
Collapse
Affiliation(s)
- Hiroshi Kishikawa
- Department of Gastroenterology, Ichikawa General Hospital, Tokyo Dental College, Ichikawa 272-8513, Chiba, Japan
| | - Jiro Nishida
- Department of Gastroenterology, Ichikawa General Hospital, Tokyo Dental College, Ichikawa 272-8513, Chiba, Japan
| |
Collapse
|
|
4
|
Yarahmadi A, Afkhami H. Potential relationship between Helicobacter pylori infection and autoimmune disorders: A narrative review. Microb Pathog 2025; 205:107572. [PMID: 40220801 DOI: 10.1016/j.micpath.2025.107572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 04/06/2025] [Accepted: 04/09/2025] [Indexed: 04/14/2025]
Abstract
Helicobacter pylori (H. pylori) is a spiral-shaped, gram-negative, flagellated bacteria that causes gastritis symptoms. This bacterium, particularly in individuals with a genetic predisposition, has been implicated in the pathogenesis of several autoimmune diseases (AD) through complex mechanisms involving the interaction of cellular and humoral immune responses. This review article tells you about the link between H. pylori infection and several types of AD, including systemic lupus erythematosus (SLE), autoimmune pancreatitis (AIP), rheumatoid arthritis (RA), Sjögren syndrome (SjS), psoriasis, and antiphospholipid syndrome (APS). We conducted a comprehensive analysis of the current literature to elucidate the potential role of H. pylori as a triggering factor for these disorders. Our findings suggest a significant correlation between H. pylori infection and the onset or exacerbation of specific ADs. This relationship is common mechanisms, including molecular mimicry, chronic inflammation, epitope spreading, and cytokine dysregulation. While H. pylori is implicated in AD, other factors such as genetic predisposition, environmental triggers, and other microbial agents also play crucial roles. Other pathogens, such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), and bacteria like Mycobacterium tuberculosis and Chlamydia pneumoniae have been linked to ADs. These shared pathways highlight the potential role of H. pylori as a unifying factor in the pathogenesis of diverse ADs. Further research is necessary to fully understand the interactions between H. pylori and the immune system in the context of autoimmunity. This review aims to provide a detailed overview of the knowledge on this topic, highlighting the need for additional studies to clarify these complex relationships.
Collapse
Affiliation(s)
- Aref Yarahmadi
- Department of Biology, Khorramabad Branch, Islamic Azad University, Khorramabad, Iran
| | - Hamed Afkhami
- Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran; Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran; Department of Medical Microbiology, Faculty of Medicine, Shahed University, Tehran, Iran.
| |
Collapse
|
|
5
|
Ihara T, Kushima R, Haruma K. Enhanced activity of autoimmune gastritis following Helicobacter pylori eradication therapy. Clin J Gastroenterol 2025; 18:258-268. [PMID: 39806234 DOI: 10.1007/s12328-024-02092-w] [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] [Received: 09/23/2024] [Accepted: 12/23/2024] [Indexed: 01/16/2025]
Abstract
The relationship between autoimmune gastritis (AIG) and Helicobacter pylori (H. pylori) gastritis remains unclear, particularly whether there is any interaction. Herein, we report a case of early-stage AIG diagnosed in an elderly patient with highly active H. pylori gastritis, who subsequently underwent eradication therapy. We were able to follow the changes in these two types of gastritis immediately before and after eradication therapy, through observation over a period of 5 years and 5 months. Despite the previous state of predominant H. pylori gastritis, eradication therapy led to rapid exacerbation of atrophic changes, which was especially evident in endoscopic findings. In addition, the anti-parietal cell antibody titer increased constantly from 1:320 to 1:1280. We concluded that AIG activity was enhanced compared to that before eradication therapy. This course suggests the following two possibilities: early-stage AIG may have progressed steadily regardless of H. pylori gastritis status, or its activity may have been suppressed until the time of eradication therapy.
Collapse
Affiliation(s)
| | - Ryoji Kushima
- Department of Pathology, Shiga University of Medical Science, Shiga, Japan
| | - Ken Haruma
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| |
Collapse
|
|
6
|
Amalia R, Miftahussurur M, Syam AF, Uchida T, Alfaray RI, Fauzia KA, Rezkitha YAA, Akada J, Matsumoto T, Yamaoka Y. Parietal Cell Antibody Levels Among Chronic Gastritis Patients in a Country With Low Helicobacter pylori Infection: Epidemiology, Histopathological Features, and H. pylori Infection. Helicobacter 2025; 30:e70035. [PMID: 40249164 DOI: 10.1111/hel.70035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 03/28/2025] [Accepted: 04/04/2025] [Indexed: 04/19/2025]
Abstract
BACKGROUND Despite the low prevalence of Helicobacter pylori in Indonesia, the high incidence of gastritis, predominantly atrophic gastritis, suggests that factors such as autoimmune gastritis (AIG) contribute to this unusual pattern. This study aims to investigate the epidemiology of AIG, histopathology, and its association with H. pylori status in Indonesia. METHODS A cross-sectional study was conducted in various regions in Indonesia between 2014 and 2017; 380 eligible sera and gastric biopsies were available when this study was conducted. As many as 138 sera samples were included in this study based on the initial examination by the updated Sydney system. The diagnosis of AIG was confirmed by serologic testing for parietal-cell antibodies (PCA) and detailed histopathological assessment with sparing of antrum histopathological features. RESULTS Among the included samples in this study, 78.99% (109/138) were PCA positive (≥ 10 RU/mL) and 0.72% (1/138) were considered to be diagnosed as AIG (spared from antrum histopathological features). The majority of PCA positive cases were H. pylori positive (61/109; 55.96%) with a significant correlation (p < 0.05, R = 0.31). Additionally, a significant association was found between H. pylori infection and PCA level with gastric histopathological features (p < 0.05). CONCLUSION This study demonstrates that the incidence of gastritis without H. pylori infection in Indonesia is not attributable to AIG, as only a single AIG-positive case was found. These findings underscore the important role of H. pylori as a pathogenic factor in chronic gastritis and highlight its mechanisms in triggering immune responses and driving disease progression and histopathological changes.
Collapse
Affiliation(s)
- Rizki Amalia
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
- Helicobacter pylori and Microbiota Study Group, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
| | - Muhammad Miftahussurur
- Helicobacter pylori and Microbiota Study Group, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine-Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya, Indonesia
| | - Ari Fahrial Syam
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine-Cipto Mangunkusumo Teaching Hospital, University of Indonesia, Jakarta, Indonesia
| | - Tomohisa Uchida
- Department of Advanced Medical Sciences, Faculty of Medicine, Oita University, Yufu, Japan
| | - Ricky Indra Alfaray
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
- Helicobacter pylori and Microbiota Study Group, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
| | - Kartika Afrida Fauzia
- Research Center for Preclinical and Clinical Medicine, National Research and Innovation Agency, Bogor, Indonesia
| | - Yudith Annisa Ayu Rezkitha
- Department of Internal Medicine, Faculty of Medicine, Universitas Muhammadiyah Surabaya, Surabaya, Indonesia
| | - Junko Akada
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
| | - Takashi Matsumoto
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
| | - Yoshio Yamaoka
- Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Japan
- Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine-Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya, Indonesia
- Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, Texas, USA
- Research Center for Global and Local Infectious Diseases, Oita University, Yufu, Japan
| |
Collapse
|
|
7
|
Saviano A, Morabito Loprete MR, Pignataro G, Piccioni A, Gasbarrini A, Franceschi F, Candelli M. Helicobacter pylori, Atherosclerosis, and Coronary Artery Disease: A Narrative Review. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:346. [PMID: 40005462 PMCID: PMC11857399 DOI: 10.3390/medicina61020346] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Revised: 02/11/2025] [Accepted: 02/14/2025] [Indexed: 02/27/2025]
Abstract
Coronary artery disease (CAD) is one of the leading causes of death worldwide, significantly contributing to mortality in both developed and developing nations. CAD arises from a combination of risk factors, including atherosclerosis, dyslipidemia, hypertension, diabetes, and smoking. In recent years, growing evidence has suggested a potential link between infectious agents and cardiovascular diseases. Among these, Helicobacter pylori (H. pylori) infection has been hypothesized for over a decade to play a role in the pathogenesis of CAD. This hypothesis is based on the bacterium's ability to trigger host inflammatory or autoimmune responses, potentially contributing to the progression of atherosclerotic plaques and coronary events. The association between H. pylori infection and CAD is of considerable interest as it opens new avenues for prevention and management strategies in cardiovascular health. Understanding this relationship could lead to innovative approaches to reducing the burden of CAD, particularly in populations with a high prevalence of H. pylori. In this review, we aim to provide a comprehensive overview of the most recent evidence on the involvement of H. pylori in the development and prognosis of CAD. By analyzing and synthesizing current findings, we seek to shed light on unresolved questions and clarify the ambiguous aspects of this potential connection. Our goal is to contribute to a deeper understanding of how H. pylori, may influence cardiovascular disease and to inspire further research in this critical area.
Collapse
Affiliation(s)
- Angela Saviano
- Emergency, Anesthesiological and Reanimation Sciences Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy; (A.S.); (M.R.M.L.); (G.P.); (A.P.); (F.F.)
| | - Maria Rita Morabito Loprete
- Emergency, Anesthesiological and Reanimation Sciences Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy; (A.S.); (M.R.M.L.); (G.P.); (A.P.); (F.F.)
| | - Giulia Pignataro
- Emergency, Anesthesiological and Reanimation Sciences Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy; (A.S.); (M.R.M.L.); (G.P.); (A.P.); (F.F.)
| | - Andrea Piccioni
- Emergency, Anesthesiological and Reanimation Sciences Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy; (A.S.); (M.R.M.L.); (G.P.); (A.P.); (F.F.)
| | - Antonio Gasbarrini
- Medical and Surgical Science Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy;
| | - Francesco Franceschi
- Emergency, Anesthesiological and Reanimation Sciences Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy; (A.S.); (M.R.M.L.); (G.P.); (A.P.); (F.F.)
| | - Marcello Candelli
- Emergency, Anesthesiological and Reanimation Sciences Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy; (A.S.); (M.R.M.L.); (G.P.); (A.P.); (F.F.)
| |
Collapse
|
|
8
|
Zhao H, Wang Y, Ren J. Helicobacter pylori and rheumatoid arthritis: Investigation of relation from traditional Chinese medicine. Microb Pathog 2025; 199:107239. [PMID: 39708982 DOI: 10.1016/j.micpath.2024.107239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Revised: 12/09/2024] [Accepted: 12/17/2024] [Indexed: 12/23/2024]
Abstract
Rheumatoid arthritis (RA) is an autoimmune condition that predominantly affects synovial joints, manifesting with joint swelling, pain, and stiffness. In advanced stages, unchecked inflammation can inflict damage on bone and cartilage, resulting in disabilities and deformities of the joints. Additionally, systemic and extra-articular complications may arise due to the consequences of uncontrolled inflammation. Helicobacter pylori (H. pylori) is one of the most prevalent chronic bacterial infections in humans. This microorganism is a spiral-shaped, flagellated, microaerophilic gram-negative bacterium. Prolonged exposure leads to the activation of the immune system, with infected gastric mucosa epithelial cells continuously producing cytokines. This production, in turn, triggers the generation of antibodies as well as T Helper 1 and T Helper 2 effector T cells. The persistent antigenic stimulation resulting from H. pylori infection could lead to the progression of autoimmune diseases. Numerous clinical and pharmacological trials have illustrated the efficacy of traditional Chinese medicine against H. pylori. This review aims to delve into the connection between H. pylori and rheumatoid arthritis so as understand the pathogenesis. The concluding section of this review explores the interplay of Chinese medicine and Helicobacter pylori concerning rheumatoid arthritis.
Collapse
Affiliation(s)
- Hua Zhao
- Department of Rheumatism and Immunology, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), No.4, Renmin Road, Shibei District, Qingdao, 266033, China
| | - Yige Wang
- Shandong University of Traditional Chinese Medicine, No.16369, Jingshi Road, Lixia District, Jinan, 250013, China
| | - Jiahui Ren
- Department of Rheumatism and Immunology, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), No.4, Renmin Road, Shibei District, Qingdao, 266033, China
| |
Collapse
|
|
9
|
Chi YC, Hsieh HM, Chang WS, Lee MS, Lin CH, Lin KD, Kuo FC, Wu DC, Sheu SJ. Helicobacter pylori and Its Treatment Impact on Immune-Mediated Ocular Diseases. Ocul Immunol Inflamm 2024; 32:2467-2478. [PMID: 39360963 DOI: 10.1080/09273948.2024.2411299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Revised: 09/21/2024] [Accepted: 09/26/2024] [Indexed: 11/28/2024]
Abstract
PURPOSE Helicobacter pylori (HP), which colonizes exclusively in the gastrointestinal tract, has been reported to dysregulate the immune response and gives rise to several extra-gastrointestinal autoimmune disorders. However, the relationship between HP and immune-mediated ocular diseases remains ambiguous. This study aims to clarify the association between immune-mediated ocular diseases and HP infection, as well as the impact of HP treatment on the incidence of immune-mediated ocular diseases. METHODS This is a retrospective population-based study using National Health Insurance Research Database in Taiwan. Patients with newly diagnosed peptic ulcer disease or HP infection between 2009 and 2015 were identified as HP group and compared to the non-HP group with one-to-one exact matching. Moreover, the incident risk of immune-mediated ocular diseases and its two subgroups (ocular surface and orbital inflammation group, intraocular inflammation group) were compared in HP patients with or without treatment. RESULTS A total of 1,030,119 subjects in the non-HP group and 1,030,119 patients in the HP group were enrolled. The incidence rate of immune-mediated ocular diseases was significantly higher in the HP group (95% confidence interval (CI): 2.534-2.547). The incident rate ratio was significantly higher in HP with treatment than without treatment (HR: 1.654, 95% CI: 1.641-1.668). The Cox proportional hazards regression model demonstrated a significantly increased HR of immune-mediated ocular diseases in HP treated group (HR: 2.265, 95% CI: 2.024-2.534) and less increased HR in HP non-treated group (HR: 1.427, 95% CI: 1.273-1.598) when comparing to non-HP group. Subgroup analysis demonstrated a significantly higher incidence rate of ocular surface and orbital inflammation as well as intraocular inflammation in the HP group. CONCLUSION This study illustrated a higher incidence of immune-mediated ocular diseases in HP infection, and a heightened risk following HP eradication.
Collapse
Affiliation(s)
- Yi-Chun Chi
- Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Hui-Min Hsieh
- Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Medical Statistics and Bioinformatics, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Center for Big Data Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wei-Shan Chang
- Division of Medical Statistics and Bioinformatics, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Sheng Lee
- Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chih-Hao Lin
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Kun-Der Lin
- Department of Internal Medicine, The Lin's Clinic, Kaohsiung, Taiwan
| | - Fu-Chen Kuo
- Department of Obstetrics and Gynecology, E-Da Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Deng-Chyang Wu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Medical University Gangshan Hospital, Kaohsiung, Taiwan
| | - Shwu-Jiuan Sheu
- Department of Ophthalmology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Ophthalmology, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| |
Collapse
|
|
10
|
He Y, Mohapatra G, Asokan S, Nobs SP, Elinav E. Microbiome modulation of antigen presentation in tolerance and inflammation. Curr Opin Immunol 2024; 91:102471. [PMID: 39277909 DOI: 10.1016/j.coi.2024.102471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 08/24/2024] [Accepted: 08/27/2024] [Indexed: 09/17/2024]
Abstract
The microbiome regulates mammalian immune responses from early life to adulthood. Antigen presentation, orchestrating these responses, integrates commensal and pathogenic signals. However, the temporal and spatial specificity of microbiome impacts on antigen presentation and downstream tolerance versus inflammation remain incompletely understood. Herein, we review the influences of antigen presentation of microbiome-related epitopes on immunity; impacts of microbiome-based modulation of antigen presentation on innate and adaptive immune responses; and their ramifications on homeostasis and immune-related disease, ranging from auto-inflammation to tumorigenesis. We highlight mechanisms driving these influences, such as 'molecular mimicry', in which microbiome auto-antigen presentation aberrantly triggers an immune response driving autoimmunity or influences conferred by microbiome-derived metabolites on antigen-presenting cells in inflammatory bowel disease. We discuss unknowns, controversies, and challenges associated with the study of microbiome regulation of antigen presentation while demonstrating how increasing knowledge may contribute to the development of microbiome-based therapeutics modulating immune responses in a variety of clinical contexts.
Collapse
Affiliation(s)
- Yiming He
- Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel
| | - Gayatree Mohapatra
- Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel
| | - Sahana Asokan
- Microbiome & Cancer Division, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Samuel Philip Nobs
- Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
| | - Eran Elinav
- Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel; Microbiome & Cancer Division, German Cancer Research Center (DKFZ), Heidelberg, Germany.
| |
Collapse
|
|
11
|
Soykan İ, Er RE, Baykara Y, Kalkan C. Unraveling the Mysteries of Autoimmune Gastritis. THE TURKISH JOURNAL OF GASTROENTEROLOGY : THE OFFICIAL JOURNAL OF TURKISH SOCIETY OF GASTROENTEROLOGY 2024; 36:135-144. [PMID: 39632655 PMCID: PMC11899966 DOI: 10.5152/tjg.2024.24563] [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: 09/26/2024] [Accepted: 11/04/2024] [Indexed: 12/07/2024]
Abstract
Autoimmune gastritis is an immune-mediated disease characterized by the destruction of parietal cells and atrophy of the oxyntic mucosa due to anti-parietal cell antibodies. It may lead to serious conditions including iron/vitamin B12 and micronutrient deficiencies, neurological disorders, and gastric malignancies. The exact mechanism of this disease is not exactly understood; however, dysregulated immunological mechanisms appear to be major contributors. Patients with this disease are often asymptomatic but may present with gastrointestinal symptoms and/or iron/vitamin B12 deficiencies. Although important serological markers are available and despite advanced endoscopic techniques, the definitive diagnosis relies on histopathological examination of gastric corporal biopsy specimens. Autoimmune gastritis is closely related with increased risk of gastric neuroendocrine tumors and gastric adenocarcinoma. Patients with autoimmune gastritis do not benefit from specific treatments, thus, management is directed to restore micronutrient deficiencies and to prevent occurrence of neoplastic transformation with appropriate endoscopic surveillance.
Collapse
Affiliation(s)
- İrfan Soykan
- Ankara University Medical School, İbn-i Sina Hospital, Gastroenterology, Ankara, Türkiye
| | - Ramazan Erdem Er
- Ankara University Medical School, İbn-i Sina Hospital, Gastroenterology, Ankara, Türkiye
| | - Yigit Baykara
- Department of Pathology, Stanford Medicine, Transfusion Medicine and Blood Banking, California, USA
| | - Cağdaş Kalkan
- Department of Gastroenterology, Ministry of Health, Bilkent City Hospital, Çankaya, Ankara, Türkiye
| |
Collapse
|
|
12
|
Lamminpää I, Boem F, Amedei A. Health-promoting worms? Prospects and pitfalls of helminth therapy. Bioessays 2024; 46:e2400080. [PMID: 39263744 DOI: 10.1002/bies.202400080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 08/28/2024] [Accepted: 09/02/2024] [Indexed: 09/13/2024]
Abstract
In this manuscript, we explore the potential therapeutic use of helminths. After analyzing helminths' role in connection with human health from the perspective of their symbiotic and evolutionary relationship, we critically examine some studies on their therapeutic applications. In doing so, we focus on some prominent mechanisms of action and potential benefits, but also on the exaggerations and theoretical and methodological difficulties of such proposals. We conclude that further studies are needed to fully explore the potential benefits of this perspective, and we encourage the scientific community in doing so.
Collapse
Affiliation(s)
- Ingrid Lamminpää
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Federico Boem
- Institut für Philosophie I, Ruhr-Universität Bochum, Bochum, Germany
| | - Amedeo Amedei
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
- Interdisciplinary Internal Medicine Unit, Careggi University Hospital, Florence, Italy
| |
Collapse
|
|
13
|
Ma XZ, Zhou N, Luo X, Guo SQ, Mai P. Update understanding on diagnosis and histopathological examination of atrophic gastritis: A review. World J Gastrointest Oncol 2024; 16:4080-4091. [DOI: 10.4251/wjgo.v16.i10.4080] [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] [Received: 03/13/2024] [Revised: 08/14/2024] [Accepted: 08/21/2024] [Indexed: 09/26/2024] Open
Abstract
Chronic atrophic gastritis (CAG) is a complex syndrome in which long-term chronic inflammatory stimulation causes gland atrophy in the gastric mucosa, reducing the stomach's ability to secrete gastric juice and pepsin, and interfering with its normal physiological function. Multiple pathogenic factors contribute to CAG incidence, the most common being Helicobacter pylori infection and the immune reactions resulting from gastric autoimmunity. Furthermore, CAG has a broad spectrum of clinical manifestations, including gastroenterology and extra-intestinal symptoms and signs, such as hematology, neurology, and oncology. Therefore, the initial CAG evaluation should involve the examination of clinical and serological indicators, as well as diagnosis confirmation via gastroscopy and histopathology if necessary. Depending on the severity and scope of atrophy affecting the gastric mucosa, a histologic staging system (Operative Link for Gastritis Assessment or Operative Link on Gastritis intestinal metaplasia) could also be employed. Moreover, chronic gastritis has a higher risk of progressing to gastric cancer (GC). In this regard, early diagnosis, treatment, and regular testing could reduce the risk of GC in CAG patients. However, the optimal interval for endoscopic monitoring in CAG patients remains uncertain, and it should ideally be tailored based on individual risk evaluations and shared decision-making processes. Although there have been many reports on CAG, the precise etiology and histopathological features of the disease, as well as the diagnosis of CAG patients, are yet to be fully elucidated. Consequently, this review offers a detailed account of CAG, including its key clinical aspects, aiming to enhance the overall understanding of the disease.
Collapse
Affiliation(s)
- Xiu-Zhen Ma
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of Gastroenterology, Gansu Provincial People's Hospital, Lanzhou 730000, Gansu Province, China
| | - Ni Zhou
- Department of Gastroenterology, Xi'an International Medical Center, Xi’an 710000, Shaanxi Province, China
| | - Xiu Luo
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Si-Qi Guo
- Department of Gastroenterology, Gansu Provincial People's Hospital, Lanzhou 730000, Gansu Province, China
- The First School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
| | - Ping Mai
- The First School of Clinical Medicine, Lanzhou University, Lanzhou 730000, Gansu Province, China
- Department of Gastroenterology, Gansu Provincial People's Hospital, Lanzhou 730000, Gansu Province, China
| |
Collapse
|
|
14
|
Farinati F, Pelizzaro F. Gastric cancer screening in Western countries: A call to action. Dig Liver Dis 2024; 56:1653-1662. [PMID: 38403513 DOI: 10.1016/j.dld.2024.02.008] [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] [Received: 01/25/2024] [Revised: 02/11/2024] [Accepted: 02/12/2024] [Indexed: 02/27/2024]
Abstract
Gastric cancer is a major cause of cancer-related death worldwide, despite the reduction in its incidence. The disease is still burdened with a poor prognosis, particularly in Western countries. The main risk factor is the infection by Helicobacter pylori, classified as a class I carcinogen by the IARC, and It is well-known that primary prevention of gastric cancer can be achieved with the eradication of the infection. Moreover, non-invasive measurement of pepsinogens (PGI and PGI/PGII ratio) allows the identification of patients that should undergo upper gastrointestinal (GI) endoscopy. Gastric non-cardia adenocarcinoma is indeed preceded by a well-defined precancerous process that involves consecutive stages, described for the first time by Correa et al. more than 40 years ago, and patients with advance stages of gastric atrophy/intestinal metaplasia and with dysplastic changes should be followed-up periodically with upper GI endoscopies. Despite these effective screening and surveillance methods, national-level screening campaigns have been adopted only in few countries in eastern Asia (Japan and South Korea). In this review, we describe primary and secondary preventive measures for gastric cancer, discussing the need to introduce screening also in Western countries. Moreover, we propose a simple algorithm for screening that could be easily applied in clinical practice.
Collapse
Affiliation(s)
- Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Via Giustiniani 2, Padova 35128, Italy; Gastroenterology Unit, Azienda Ospedale-Università di Padova, Via Giustiniani 2, Padova 35128, Italy.
| | - Filippo Pelizzaro
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Via Giustiniani 2, Padova 35128, Italy; Gastroenterology Unit, Azienda Ospedale-Università di Padova, Via Giustiniani 2, Padova 35128, Italy
| |
Collapse
|
|
15
|
Kazantseva EP, Frolov AM, Frolov MA, Novikova EA, Mugulov KS, Kozlova KS, Volchanskiy KI, Maximova SA, Pilipenko MO. The role of Helicobacter pylori in the development of inflammatory eyelid diseases. ACTA BIOMEDICA SCIENTIFICA 2024; 9:108-116. [DOI: 10.29413/abs.2024-9.4.13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Background. Blepharitis is one of the most common eye diseases: it accounts for 23.3 % of the total number of patients with inflammatory eye diseases worldwide. 40.2 % of these patients seek outpatient care. The incidence of blepharitis is 1.5–2 times higher in women than in men. The leading factors in the development of blepharitis are both general (gastrointestinal tract diseases, diabetes mellitus, hypertension, systemic use of corticosteroids, etc.) and local (atopic and seborrheic dermatitis or rosacea). The main causative agents of this disease are Staphylococcus spp. (S. aureus, S. epidermidis). As a rule, the disease manifests itself in patients aged 30–50 years, while in women aged 40 to 45 years, 80 % of blepharitis are of staphylococcal origin. Currently, there are reports in the literature about apotential link between Helicobacter pylori infection and the development of chronic blepharitis, but the data are very contradictory.The aim of the study. To analyze the features of the relationship between Helicobacter pylori and inflammatory eyelid diseases.Materials and methods. We conducted a search and analysis of literary sources in the Web of Science, PubMed and Google Scholar databases, as well as in the Russian Science Citation Index database for the period from 2000 to 2022.Conclusion. The review analyzes and summarizes the pathogenic mechanisms of the relationship between chronic blepharitis and Helicobacter pylori. We carried out an analysis of numerous studies, which give grounds to assume a possible role of Helicobacter pylori infection in the development and course of inflammatory eyelid diseases (blepharitis). The main pathogenic aspects in these studies are: chronic inflammation of the eyelids and gastrointestinal tract (antigenic mimicry); excretion of toxic substances from the oral cavity (ammonia, hydrogen nitrite, hydrogen cyanide and other substances causing indirect inflammation of the conjunctiva and eyelid cartilage); the presence of Helicobacter pylori in tears.
Collapse
Affiliation(s)
- E. P. Kazantseva
- Peoples’ Friendship University of Russia named after Patrice Lumumba
| | - A. M. Frolov
- Peoples’ Friendship University of Russia named after Patrice Lumumba
| | - M. A. Frolov
- Peoples’ Friendship University of Russia named after Patrice Lumumba
| | - E. A. Novikova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - K. S. Mugulov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - K. S. Kozlova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - K. I. Volchanskiy
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - S. A. Maximova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - M. O. Pilipenko
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| |
Collapse
|
|
16
|
Granot M, Beinvogl BC, Schvimer M, Goldsmith JD, Matar M, Ben Tov A, Feler AY, Nachum N, Morgenstern S, Mayer C, Shamir R, Weiss B, Shouval DS. Clinical characteristics and outcomes of pediatric patients with autoimmune gastritis. J Pediatr Gastroenterol Nutr 2024; 79:501-509. [PMID: 39010761 DOI: 10.1002/jpn3.12318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Revised: 06/23/2024] [Accepted: 07/02/2024] [Indexed: 07/17/2024]
Abstract
OBJECTIVES Autoimmune gastritis (AIG) is a rare chronic inflammatory disorder with potential long-term sequelae including gastric neoplasia. There is limited data on the natural history of pediatric AIG. We aimed to characterize the clinical course and outcomes of children with AIG. METHODS This was a multicenter retrospective study that included pediatric patients diagnosed with AIG between January 1, 2000 and December 31, 2021. Diagnosis of AIG was based on the demonstration of histological corpus-predominant atrophic gastritis, with or without positive antiparietal cell (APCA) or anti-intrinsic factor (IF) antibodies. Demographic, clinical, laboratory, endoscopic, and histologic data were retrieved, along with follow-up data. RESULTS Thirty-three patients, (23 females [69.7%], median age 12.0 [interquartile range 7.0-15.0] years at diagnosis) were identified. Twenty-two patients (66.7%) had positive APCA and/or anti-IF serology. The most common presenting manifestation was iron deficiency anemia (75%), and accompanying autoimmune disorders were significantly more common in patients with positive serology (62% vs. 18%, p < 0.05). Pseudo-pyloric or intestinal-type metaplasia was present at diagnosis in eight patients (24%), and 11 additional patients (33%) developed metaplasia during a median follow-up time of 27 (17.5-48.3) months. One patient developed a type 1 gastric neuroendocrine tumor. Helicobacter pylori was identified in only one patient, while two patients had prior eradication. Endoscopic and histologic improvements weren't identified in any patients. CONCLUSIONS AIG should be considered in patients with autoimmunity and resistant iron-deficiency anemia. H. pylori infection may not be associated with pediatric AIG. The development of neuroendocrine tumor in one patient, and the high rates of metaplasia, highlight the importance of surveillance.
Collapse
Affiliation(s)
- Maya Granot
- Pediatric Gastroenterology and Nutrition Unit, Edmond and Lily Safra Children's Hospital, Ramat Gan, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Beate C Beinvogl
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Michael Schvimer
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Pathology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Jeffrey D Goldsmith
- Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Manar Matar
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Gastroenterology, Nutrition, and Liver Diseases, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
| | - Amir Ben Tov
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Pediatric Gastroenterology Institute, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Anat Y Feler
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Pediatric Gastroenterology Institute, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Nurit Nachum
- Pediatric Gastroenterology and Nutrition Unit, Edmond and Lily Safra Children's Hospital, Ramat Gan, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Sara Morgenstern
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Pathology, Rabin Medical Center, Petah Tikva, Israel
| | - Chen Mayer
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Pathology, Sheba Medical Center, Tel Hashomer, Ramat Gan, Israel
| | - Raanan Shamir
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Gastroenterology, Nutrition, and Liver Diseases, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
| | - Batia Weiss
- Pediatric Gastroenterology and Nutrition Unit, Edmond and Lily Safra Children's Hospital, Ramat Gan, Israel
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Dror S Shouval
- Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
- Institute of Gastroenterology, Nutrition, and Liver Diseases, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
| |
Collapse
|
|
17
|
Bazin T, Nozeret K, Julié C, Lamarque D, Touati E. Protein Biomarkers of Gastric Preneoplasia and Cancer Lesions in Blood: A Comprehensive Review. Cancers (Basel) 2024; 16:3019. [PMID: 39272877 PMCID: PMC11394471 DOI: 10.3390/cancers16173019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 08/20/2024] [Accepted: 08/23/2024] [Indexed: 09/15/2024] Open
Abstract
Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. It is often associated with a bad prognosis because of its asymptomatic phenotype until advanced stages, highlighting the need for its prevention and early detection. GC development is preceded by the emergence of gastric preneoplasia lesions (GPNLs), namely atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia (DYS). GC is currently diagnosed by endoscopy, which is invasive and costly and has limited effectiveness for the detection of GPNLs. Therefore, the discovery of non-invasive biomarkers in liquid biopsies, such as blood samples, in order to identify the presence of gastric preneoplasia and/or cancer lesions at asymptomatic stages is of paramount interest. This comprehensive review provides an overview of recently identified plasma/serum proteins and their diagnostic performance for the prediction of GPNLs and early cancer lesions. Autoantibodies appear to be promising biomarkers for AG, IM and early gastric cancer detection, along with inflammation and immunity-related proteins and antibodies against H. pylori virulence factors. There is a lack of specific protein biomarkers with which to detect DYS. Despite the need for further investigation and validation, some emerging candidates could pave the way for the development of reliable, non-invasive diagnostic tests for the detection and prevention of GC.
Collapse
Affiliation(s)
- Thomas Bazin
- Department of Gastroenterology and Nutritional Support, Center for Intestinal Failure, Reference Centre of Rare Disease MarDI, Assistance Publique-Hôpitaux de Paris (AP-HP) Beaujon Hospital, University Paris Cité, F-92110 Clichy, France
- Infection & Inflammation, Unité Mixte de Recherche (UMR) 1173, Inserm, Université de Versailles-Saint-Quentin-en-Yvelines (UVSQ)/Université Paris Saclay, F-78180 Montigny-le-Bretonneux, France
| | - Karine Nozeret
- Équipe DMic01-Infection, Génotoxicité et Cancer, Département de Microbiologie, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 6047, Institut Pasteur, Université Paris Cité, F-75015 Paris, France
| | - Catherine Julié
- Department of Anatomical Pathology, Université Paris Saclay/Université de Versailles-Saint-Quentin-en-Yvelines (UVSQ), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Ambroise Paré, F-92100 Boulogne-Billancourt, France
| | - Dominique Lamarque
- Infection & Inflammation, Unité Mixte de Recherche (UMR) 1173, Inserm, Université de Versailles-Saint-Quentin-en-Yvelines (UVSQ)/Université Paris Saclay, F-78180 Montigny-le-Bretonneux, France
- Department of Gastroenterology, Université Paris Saclay/Université de Versailles-Saint-Quentin-en-Yvelines (UVSQ), Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Ambroise Paré, F-92100 Boulogne Billancourt, France
| | - Eliette Touati
- Équipe DMic01-Infection, Génotoxicité et Cancer, Département de Microbiologie, Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 6047, Institut Pasteur, Université Paris Cité, F-75015 Paris, France
| |
Collapse
|
|
18
|
Vavallo M, Cingolani S, Cozza G, Schiavone FP, Dottori L, Palumbo C, Lahner E. Autoimmune Gastritis and Hypochlorhydria: Known Concepts from a New Perspective. Int J Mol Sci 2024; 25:6818. [PMID: 38999928 PMCID: PMC11241626 DOI: 10.3390/ijms25136818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Revised: 06/18/2024] [Accepted: 06/19/2024] [Indexed: 07/14/2024] Open
Abstract
Autoimmune atrophic gastritis is an immune-mediated disease resulting in autoimmune destruction of the specialized acid-producing gastric parietal cells. As a consequence, in autoimmune atrophic gastritis, gastric acid secretion is irreversibly impaired, and the resulting hypochlorhydria leads to the main clinical manifestations and is linked, directly or indirectly, to the long-term neoplastic complications of this disease. In the last few years, autoimmune atrophic gastritis has gained growing interest leading to the acquisition of new knowledge on different aspects of this disorder. Although reliable serological biomarkers are available and gastrointestinal endoscopy techniques have substantially evolved, the diagnosis of autoimmune atrophic gastritis is still affected by a considerable delay and relies on histopathological assessment of gastric biopsies. One of the reasons for the diagnostic delay is that the clinical presentations of autoimmune atrophic gastritis giving rise to clinical suspicion are very different, ranging from hematological to neurological-psychiatric up to gastrointestinal and less commonly to gynecological-obstetric symptoms or signs. Therefore, patients with autoimmune atrophic gastritis often seek advice from physicians of other medical specialties than gastroenterologists, thus underlining the need for increased awareness of this disease in a broad medical and scientific community.
Collapse
Affiliation(s)
| | | | | | | | | | | | - Edith Lahner
- Gastroenterology Unit, Sant’Andrea University Hospital, Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, 00189 Rome, Italy (G.C.); (F.P.S.)
| |
Collapse
|
|
19
|
Angerilli V, Vanoli A, Celin G, Ceccon C, Gasparello J, Sabbadin M, De Lisi G, Paudice M, Lenti MV, Rovedatti L, Di Sabatino A, Bazzocchi F, Lonardi S, Savarino E, Luchini C, Parente P, Grillo F, Mastracci L, Fassan M. Gastric Carcinoma in Autoimmune Gastritis: A Histopathologic and Molecular Study. Mod Pathol 2024; 37:100491. [PMID: 38588886 DOI: 10.1016/j.modpat.2024.100491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Revised: 03/04/2024] [Accepted: 04/02/2024] [Indexed: 04/10/2024]
Abstract
Patients with autoimmune gastritis (AIG) have a 13-fold risk of developing type-1 neuroendocrine tumors, whereas the risk for gastric adenocarcinoma is still uncertain. Here we describe the clinicopathologic and molecular features of a series of gastric carcinomas (GC) arising in the context of AIG. A total of 26 AIG-associated GC specimens were collected from 4 Italian Institutions. Immunohistochemistry for MUC1, MUC2, MUC5AC, MUC6, CDX2, HER2, PD-L1, CLDN18, mismatch repair (MMR) proteins, and p53 and EBV-encoded RNA (EBER) in situ hybridization were performed. Histologic and immunohistochemical features were jointly reviewed by 5 expert gastrointestinal pathologists. Next-generation sequencing analysis (TrueSight Oncology 500, Illumina) of 523 cancer-related genes was performed on 19 cases. Most tumors were diagnosed as pT1 (52%) and they were located in the corpus/fundus (58%) and associated with operative link for gastritis assessment stage II gastritis (80.8%), absence of parietal cells, complete intestinal metaplasia, and enterochromaffin-like-cell micronodular hyperplasia. Only 4 (15.4%) GCs were diagnosed during follow-up for AIG. The following histotypes were identified: 20 (77%) adenocarcinomas; 3 (11%) mixed neuroendocrine-non-neuroendocrine neoplasms, and 2 (8%) high-grade solid adenocarcinomas with focal neuroendocrine component, 1 (4%) adenocarcinoma with an amphicrine component. Overall, 7 cases (27%) showed MMR deficiency, 3 (12%) were positive (score 3+) for HER2, 6 (23%) were CLDN18 positive, and 11 (42%) had PD-L1 combined positive score ≥ 10. EBER was negative in all cases. Molecular analysis revealed 5/19 (26%) microsatellite instability (MSI) cases and 7 (37%) tumor mutational burden (TMB) high. The most frequently altered genes were TP53 (8/19, 42%), RNF43 (7/19, 37%), ERBB2 (7/19, 37% [2 amplified and 5 mutated cases]), ARID1A (6/19, 32%), and PIK3CA (4/19, 21%). In summary, AIG-associated GCs are often diagnosed at low stage in patients with longstanding misrecognized severe AIG; they often display a neuroendocrine component or differentiation, have relatively higher rates of MMR deficiency, and TMB high.
Collapse
Affiliation(s)
- Valentina Angerilli
- Department of Medicine, Surgical Pathology Unit, University of Padua, Padua, Italy
| | - Alessandro Vanoli
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia, Pavia, Italy; Anatomic Pathology Unit, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Giulia Celin
- Department of Medicine, Surgical Pathology Unit, University of Padua, Padua, Italy
| | - Carlotta Ceccon
- Department of Medicine, Surgical Pathology Unit, University of Padua, Padua, Italy
| | - Jessica Gasparello
- Department of Medicine, Surgical Pathology Unit, University of Padua, Padua, Italy
| | | | - Giuseppe De Lisi
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Michele Paudice
- Anatomic Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DICS), University of Genova, Italy; Ospedale Policlinico San Martino, IRCCS for Oncology and Neuroscience, Genova, Italy
| | - Marco Vincenzo Lenti
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; First Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Laura Rovedatti
- Gastroenterology and Digestive Endoscopy Unit, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Antonio Di Sabatino
- Department of Internal Medicine and Medical Therapeutics, University of Pavia, Pavia, Italy; First Department of Internal Medicine, IRCCS San Matteo Hospital Foundation, Pavia, Italy
| | - Francesca Bazzocchi
- Surgical Abdominal Unit, Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | - Sara Lonardi
- Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Claudio Luchini
- Department of Diagnostics and Public Health, Section of Pathology, University and Hospital Trust of Verona, Verona, Italy
| | - Paola Parente
- Pathology Unit, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy
| | - Federica Grillo
- Anatomic Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DICS), University of Genova, Italy; Ospedale Policlinico San Martino, IRCCS for Oncology and Neuroscience, Genova, Italy
| | - Luca Mastracci
- Anatomic Pathology Unit, Department of Surgical Sciences and Integrated Diagnostics (DICS), University of Genova, Italy; Ospedale Policlinico San Martino, IRCCS for Oncology and Neuroscience, Genova, Italy
| | - Matteo Fassan
- Department of Medicine, Surgical Pathology Unit, University of Padua, Padua, Italy; Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy.
| |
Collapse
|
|
20
|
Dore MP, Pes GM. Trained Immunity and Trained Tolerance: The Case of Helicobacter pylori Infection. Int J Mol Sci 2024; 25:5856. [PMID: 38892046 PMCID: PMC11172748 DOI: 10.3390/ijms25115856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2024] [Revised: 05/16/2024] [Accepted: 05/25/2024] [Indexed: 06/21/2024] Open
Abstract
Trained immunity is a concept in immunology in which innate immune cells, such as monocytes and macrophages, exhibit enhanced responsiveness and memory-like characteristics following initial contact with a pathogenic stimulus that may promote a more effective immune defense following subsequent contact with the same pathogen. Helicobacter pylori, a bacterium that colonizes the stomach lining, is etiologically associated with various gastrointestinal diseases, including gastritis, peptic ulcer, gastric adenocarcinoma, MALT lymphoma, and extra gastric disorders. It has been demonstrated that repeated exposure to H. pylori can induce trained immunity in the innate immune cells of the gastric mucosa, which become more responsive and better able to respond to subsequent H. pylori infections. However, interactions between H. pylori and trained immunity are intricate and produce both beneficial and detrimental effects. H. pylori infection is characterized histologically as the presence of both an acute and chronic inflammatory response called acute-on-chronic inflammation, or gastritis. The clinical outcomes of ongoing inflammation include intestinal metaplasia, gastric atrophy, and dysplasia. These same mechanisms may also reduce immunotolerance and trigger autoimmune pathologies in the host. This review focuses on the relationship between trained immunity and H. pylori and underscores the dynamic interplay between the immune system and the pathogen in the context of gastric colonization and inflammation.
Collapse
Affiliation(s)
- Maria Pina Dore
- Dipartimento di Medicina, Chirurgia e Farmacia, University of Sassari, Clinica Medica, Viale San Pietro 8, 07100 Sassari, Italy;
- Department of Medicine, Baylor College of Medicine, One Baylor Plaza Blvd, Houston, TX 77030, USA
| | - Giovanni Mario Pes
- Dipartimento di Medicina, Chirurgia e Farmacia, University of Sassari, Clinica Medica, Viale San Pietro 8, 07100 Sassari, Italy;
| |
Collapse
|
|
21
|
Lamberti G, Panzuto F, Pavel M, O'Toole D, Ambrosini V, Falconi M, Garcia-Carbonero R, Riechelmann RP, Rindi G, Campana D. Gastric neuroendocrine neoplasms. Nat Rev Dis Primers 2024; 10:25. [PMID: 38605021 DOI: 10.1038/s41572-024-00508-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/27/2024] [Indexed: 04/13/2024]
Abstract
Gastric neuroendocrine neoplasms (gNENs) display peculiar site-specific features among all NENs. Their incidence and prevalence have been rising in the past few decades. gNENs comprise gastric neuroendocrine carcinomas (gNECs) and gastric neuroendocrine tumours (gNETs), the latter further classified into three types. Type I anatype II gNETs are gastrin-dependent and develop in chronic atrophic gastritis and as part of Zollinger-Ellison syndrome within a multiple endocrine neoplasia type 1 syndrome (MEN1), respectively. Type III or sporadic gNETs develop in the absence of hypergastrinaemia and in the context of a near-normal or inflamed gastric mucosa. gNECs can also develop in the context of variable atrophic, relatively normal or inflamed gastric mucosa. Each gNEN type has different clinical characteristics and requires a different multidisciplinary approach in expert dedicated centres. Type I gNETs are managed mainly by endoscopy or surgery, whereas the treatment of type II gNETs largely depends on the management of the concomitant MEN1. Type III gNETs may require both locoregional approaches and systemic treatments; NECs are often metastatic and therefore require systemic treatment. Specific data regarding the systemic treatment of gNENs are lacking and are derived from the treatment of intestinal NETs and NECs. An enhanced understanding of molecular and clinical pathophysiology is needed to improve the management and outcomes of patients' gNETs.
Collapse
Affiliation(s)
- Giuseppe Lamberti
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Bologna, Italy
- Medical Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Francesco Panzuto
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, Rome, Italy
- Digestive Disease Unit, Sant'Andrea University Hospital, ENETS Center of Excellence, Rome, Italy
| | - Marianne Pavel
- Department of Medicine 1, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany
| | - Dermot O'Toole
- National Centre for Neuroendocrine Tumours, ENETS Centre of Excellence, St. Vincent's University Hospital, Dublin, Ireland
- Trinity College Dublin, St. James Hospital, Dublin, Ireland
| | - Valentina Ambrosini
- Nuclear Medicine, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Massimo Falconi
- Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Rocio Garcia-Carbonero
- Medicine Department, Universidad Complutense de Madrid, Madrid, Spain
- Oncology Department, Hospital Universitario 12 de Octubre, Imas12, Madrid, Spain
| | | | - Guido Rindi
- Section of Anatomic Pathology, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, Rome, Italy
- Department of Woman and Child Health Sciences and Public Health, Anatomic Pathology Unit, Fondazione Policlinico Universitario A. Gemelli - IRCCS, ENETS Center of Excellence, Rome, Italy
| | - Davide Campana
- Department of Medical and Surgical Sciences (DIMEC), Alma Mater Studiorum - University of Bologna, Bologna, Italy.
- Medical Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
| |
Collapse
|
|
22
|
Martinelli S, Nannini G, Cianchi F, Coratti F, Amedei A. The Impact of Microbiota-Immunity-Hormone Interactions on Autoimmune Diseases and Infection. Biomedicines 2024; 12:616. [PMID: 38540229 PMCID: PMC10967803 DOI: 10.3390/biomedicines12030616] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2023] [Revised: 02/21/2024] [Accepted: 02/25/2024] [Indexed: 02/07/2025] Open
Abstract
Autoimmune diseases are complex multifactorial disorders, and a mixture of genetic and environmental factors play a role in their onset. In recent years, the microbiota has gained attention as it helps to maintain host health and immune homeostasis and is a relevant player in the interaction between our body and the outside world. Alterations (dysbiosis) in its composition or function have been linked to different pathologies, including autoimmune diseases. Among the different microbiota functions, there is the activation/modulation of immune cells that can protect against infections. However, if dysbiosis occurs, it can compromise the host's ability to protect against pathogens, contributing to the development and progression of autoimmune diseases. In some cases, infections can trigger autoimmune diseases by several mechanisms, including the alteration of gut permeability and the activation of innate immune cells to produce pro-inflammatory cytokines that recruit autoreactive T and B cells. In this complex scenario, we cannot neglect critical hormones' roles in regulating immune responses. Different hormones, especially estrogens, have been shown to influence the development and progression of autoimmune diseases by modulating the activity and function of the immune system in different ways. In this review, we summarized the main mechanisms of connection between infections, microbiota, immunity, and hormones in autoimmune diseases' onset and progression given the influence of some infections and hormone levels on their pathogenesis. In detail, we focused on rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus.
Collapse
Affiliation(s)
- Serena Martinelli
- Department of Clinical and Experimental Medicine, University of Florence, 50139 Florence, Italy; (S.M.); (G.N.); (F.C.); (F.C.)
| | - Giulia Nannini
- Department of Clinical and Experimental Medicine, University of Florence, 50139 Florence, Italy; (S.M.); (G.N.); (F.C.); (F.C.)
| | - Fabio Cianchi
- Department of Clinical and Experimental Medicine, University of Florence, 50139 Florence, Italy; (S.M.); (G.N.); (F.C.); (F.C.)
| | - Francesco Coratti
- Department of Clinical and Experimental Medicine, University of Florence, 50139 Florence, Italy; (S.M.); (G.N.); (F.C.); (F.C.)
| | - Amedeo Amedei
- Department of Clinical and Experimental Medicine, University of Florence, 50139 Florence, Italy; (S.M.); (G.N.); (F.C.); (F.C.)
- SOD of Interdisciplinary Internal Medicine, Azienda Ospedaliera Universitaria Careggi (AOUC), 50134 Florence, Italy
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), 50139 Florence, Italy
| |
Collapse
|
|
23
|
Ren C, Carrillo ND, Cryns VL, Anderson RA, Chen M. Environmental pollutants and phosphoinositide signaling in autoimmunity. JOURNAL OF HAZARDOUS MATERIALS 2024; 465:133080. [PMID: 38091799 PMCID: PMC10923067 DOI: 10.1016/j.jhazmat.2023.133080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 11/16/2023] [Accepted: 11/22/2023] [Indexed: 02/08/2024]
Abstract
Environmental pollution stands as one of the most critical challenges affecting human health, with an estimated mortality rate linked to pollution-induced non-communicable diseases projected to range from 20% to 25%. These pollutants not only disrupt immune responses but can also trigger immunotoxicity. Phosphoinositide signaling, a pivotal regulator of immune responses, plays a central role in the development of autoimmune diseases and exhibits high sensitivity to environmental stressors. Among these stressors, environmental pollutants have become increasingly prevalent in our society, contributing to the initiation and exacerbation of autoimmune conditions. In this review, we summarize the intricate interplay between phosphoinositide signaling and autoimmune diseases within the context of environmental pollutants and contaminants. We provide an up-to-date overview of stress-induced phosphoinositide signaling, discuss 14 selected examples categorized into three groups of environmental pollutants and their connections to immune diseases, and shed light on the associated phosphoinositide signaling pathways. Through these discussions, this review advances our understanding of how phosphoinositide signaling influences the coordinated immune response to environmental stressors at a biological level. Furthermore, it offers valuable insights into potential research directions and therapeutic targets aimed at mitigating the impact of environmental pollutants on the pathogenesis of autoimmune diseases. SYNOPSIS: Phosphoinositide signaling at the intersection of environmental pollutants and autoimmunity provides novel insights for managing autoimmune diseases aggravated by pollutants.
Collapse
Affiliation(s)
- Chang Ren
- Department of Pharmacology, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China
| | - Noah D Carrillo
- Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA
| | - Vincent L Cryns
- Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA; University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA
| | - Richard A Anderson
- University of Wisconsin Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA
| | - Mo Chen
- Department of Pharmacology, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China.
| |
Collapse
|
|
24
|
Bufka J, Sýkora J, Vaňková L, Gutová V, Kačerová Š, Daum O, Schwarz J. Impact of autoimmune gastritis on chronic urticaria in paediatric patients - pathophysiological point of views. Eur J Pediatr 2024; 183:515-522. [PMID: 37947925 PMCID: PMC10912447 DOI: 10.1007/s00431-023-05324-2] [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] [Received: 10/02/2023] [Revised: 10/28/2023] [Accepted: 10/30/2023] [Indexed: 11/12/2023]
Abstract
We would like to provide an updated comprehensive perspective and identify the components linked to chronic spontaneous urticaria (CSU) without specific triggers in autoimmune atrophic gastritis (AAG). AAG is an organ-specific autoimmune disease that affects the corpus-fundus gastric mucosa. Although we lack a unified explanation of the underlying pathways, when considering all paediatric patients reported in the literature, alterations result in gastric neuroendocrine enterochromaffin-like (ECL) cell proliferation and paracrine release of histamine. Several mechanisms have been proposed for the pathogenesis of CSU, with much evidence pointing towards AAG and ECL cell responses, which may be implicated as potential factors contributing to CSU. The excessive production/release of histamine into the bloodstream could cause or trigger exacerbations of CSU in AAG, independent of Helicobacter pylori; thus, the release of histamine from ECL cells may be the primary modulator. CONCLUSION Considering the understanding of these interactions, recognising the respective roles of AAG in the pathogenesis of CSU may strongly impact the diagnostic workup and management of unexplained/refractory CSU and may inform future research and interventions in the paediatric population. WHAT IS KNOWN • Autoimmune atrophic gastritis is a chronic immune-mediated inflammatory disease characterised by the destruction of the oxyntic mucosa in the gastric body and fundus, mucosal atrophy, and metaplastic changes. • Autoimmune atrophic gastritis in paediatric patients is important because of the poor outcome and risk of malignancy and possibly underestimated entities primarily reported in single-case reports. WHAT IS NEW • Upper gastrointestinal inflammatory disorders, independent of H. pylori, have been implicated as potential inducing factors in the development of chronic spontaneous urticaria. • If a paediatric patient presents with symptoms such as anaemia, reduced vitamin B12 levels, recurrent urticaria with no other detectable aetiology, positive anti-parietal cell antibodies, and elevated gastrin levels, autoimmune atrophic gastritis should be considered a possible cause of chronic urticaria.
Collapse
Affiliation(s)
- J Bufka
- Department of Pediatrics, Faculty of Medicine in Pilsen, Faculty Hospital, Charles University in Prague, Alej Svobody 80, Pilsen, 323 00, Czech Republic.
| | - J Sýkora
- Department of Pediatrics, Faculty of Medicine in Pilsen, Faculty Hospital, Charles University in Prague, Alej Svobody 80, Pilsen, 323 00, Czech Republic
| | - L Vaňková
- Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | - V Gutová
- Department of Allergology and Immunology, Teaching Hospital in Pilsen, Pilsen, Czech Republic
| | - Š Kačerová
- Department of Allergology and Immunology, Teaching Hospital in Pilsen, Pilsen, Czech Republic
| | - O Daum
- Sikl's Department of Pathology, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | - J Schwarz
- Department of Pediatrics, Faculty of Medicine in Pilsen, Faculty Hospital, Charles University in Prague, Alej Svobody 80, Pilsen, 323 00, Czech Republic
| |
Collapse
|
|
25
|
Atzeni F, Palumbo A, Boccassini L, Sarzi-Puttini P. Helicobacter pylori Infection and Gastric Autoimmunity. INFECTION AND AUTOIMMUNITY 2024:459-471. [DOI: 10.1016/b978-0-323-99130-8.00023-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
26
|
Youn HS, Jun JS, Yeom JS, Park JS, Lim JY, Woo HO, Yang JW, Baik SC, Lee WK, Seo JH. Identification of Autoantigens in Pediatric Gastric Juices. Pediatr Gastroenterol Hepatol Nutr 2024; 27:15-25. [PMID: 38249638 PMCID: PMC10796257 DOI: 10.5223/pghn.2024.27.1.15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 03/22/2023] [Accepted: 10/27/2023] [Indexed: 01/23/2024] Open
Abstract
Purpose This study aimed to investigate the presence of autoantigens in the gastric juices of children. Methods Gastric juice and serum samples were obtained from 53 children <15 years of age who underwent gastric endoscopy. Among these, 8, 22, and 23 participants were in the age groups 0-5, 6-10, and 11-15 years, respectively. These samples were analyzed using two-dimensional electrophoresis (2-DE), immunoblot analysis, and matrix-assisted laser desorption ionization-time of-flight mass spectrometry. Furthermore, we reviewed the histopathological findings and urease test results and compared them with the results of 2-DE and immunoblot analysis. Results There were no statistically significant differences in urease test positivity, grades of chronic gastritis, active gastritis, or Helicobacter pylori infiltration of the antrum and body among the three age groups. Three distinct patterns of gastric juice were observed on 2-DE. Pattern I was the most common, and pattern III was not observed below the age of 5 years. Histopathological findings were significantly different among active gastritis (p=0.037) and H. pylori infiltration (p=0.060) in the gastric body. The immunoblots showed large spots at an approximate pH of 3-4 and molecular weights of 31-45 kDa. These distinct, large positive spots were identified as gastric lipase and pepsin A and C. Conclusion Three enzymes, which are normally secreted under acidic conditions were identified as autoantigens. Further investigation of the pathophysiology and function of autoantigens in the stomach is required.
Collapse
Affiliation(s)
- Hee-Shang Youn
- Department of Pediatrics, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Gyeongsang Institute of Health Science, Jinju, Korea
| | - Jin-Su Jun
- Department of Pediatrics, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Gyeongsang Institute of Health Science, Jinju, Korea
| | - Jung Sook Yeom
- Department of Pediatrics, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Gyeongsang Institute of Health Science, Jinju, Korea
| | - Ji Sook Park
- Department of Pediatrics, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Gyeongsang Institute of Health Science, Jinju, Korea
| | - Jae-Young Lim
- Department of Pediatrics, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Gyeongsang Institute of Health Science, Jinju, Korea
| | - Hyang-Ok Woo
- Department of Pediatrics, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Gyeongsang Institute of Health Science, Jinju, Korea
| | - Jung-Wook Yang
- Department of Pathology, Gyeongsang National University School of Medicine, Gyeongsang Institute of Health Science, Jinju, Korea
| | - Seung-Chul Baik
- Department of Microbiology, Gyeongsang National University School of Medicine, Gyeongsang Institute of Health Science, Jinju, Korea
| | - Woo-Kon Lee
- Department of Microbiology, Gyeongsang National University School of Medicine, Gyeongsang Institute of Health Science, Jinju, Korea
| | - Ji-Hyun Seo
- Department of Pediatrics, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Gyeongsang Institute of Health Science, Jinju, Korea
| |
Collapse
|
|
27
|
Kaibysheva V, Tykhonov S, Kashin S, Kuvaev R, Kraynova E, Baculina N, Fedorov E, Drapkina O. Algorithm of autoimmune gastritis diagnosis and treatment. RUSSIAN JOURNAL OF PREVENTIVE MEDICINE 2024; 27:101. [DOI: 10.17116/profmed202427091101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
28
|
Zhang Z, Zhu T, Zhang L, Xing Y, Yan Z, Li Q. Critical influence of cytokines and immune cells in autoimmune gastritis. Autoimmunity 2023; 56:2174531. [PMID: 36762543 DOI: 10.1080/08916934.2023.2174531] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/11/2023]
Abstract
Gastric cancer (GC) is a type of the most common cancers. Autoimmune gastritis (AIG) and infection with Helicobacter pylori (HP) are the risk factors of triggering GC. With the emphasis on the treatment of HP, the incidence and prevalence of HP infection in population is decreasing. However, AIG lacks accurate diagnosis and treatment methods, which occupies high cancer risk factors. AIG is controlled by the immune environment of the stomach, including immune cells, inflammatory cells, and infiltrating intercellular material. Various immune cells or cytokines play a central role in the process of regulating gastric parietal cells. Abnormal expression levels of cytokines involved in immunity are bound to face the risk of tumorigenesis. Therefore, it is particularly important for preventing or treating AIG and avoiding the risk of gastric cancer to clarify the confirmed action mode of immune cells and cytokines in the gastric system. Herein, we briefly reviewed the role of the immune environment under AIG, focussing on describing these double-edged effects between immune cells and cytokines, and pointing out potential research challenges.
Collapse
Affiliation(s)
- Zepeng Zhang
- Kunshan Hospital of Chinese Medicine, Suzhou, Jiangsu, China
| | - Tongtong Zhu
- Kunshan Hospital of Traditional Chinese and Western Medicine, Suzhou, Jiangsu, China
| | - Lei Zhang
- Kunshan Hospital of Chinese Medicine, Suzhou, Jiangsu, China
| | - Yanchao Xing
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Zhiqiang Yan
- Kunshan Hospital of Chinese Medicine, Suzhou, Jiangsu, China
| | - Qingsong Li
- Kunshan Hospital of Chinese Medicine, Suzhou, Jiangsu, China
| |
Collapse
|
|
29
|
Yu YF, Tong KK, Shangguan XL, Yang XY, Wu JY, Hu G, Yu R, Tan CC. Research status and hotspots of autoimmune gastritis: A bibliometric analysis. World J Gastroenterol 2023; 29:5781-5799. [PMID: 38075850 PMCID: PMC10701335 DOI: 10.3748/wjg.v29.i42.5781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 10/18/2023] [Accepted: 10/30/2023] [Indexed: 11/13/2023] Open
Abstract
BACKGROUND As an emerging potential risk factor for gastric cancer, autoimmune gastritis (AIG) has garnered increasing attention from researchers. AIM To analyze the research overview and popular topics in the field of AIG using bibliometrics. METHODS Relevant publications on AIG in the Web of Science Core Collection were collated, and data visualization and analysis of the number of publications, countries, institutions, journals, authors, keywords, and citations were performed using software such as VOSviewer, CiteSpace, and Scimago Graphic. RESULTS In total, 316 relevant articles were included in the analysis. From 2015 to 2022, the number of publications increased annually. The countries, institutions, authors, and journals with the highest number of publications in this field were Italy, Monash University, Toh BH, and Internal Medicine. The main keywords used in this field of research were pathogenesis, Helicobacter pylori, autoantibody, parietal cell antibody, atrophic gastritis, classification, diagnosis, autoimmune disease, risk, cancer, gastric cancer, vitamin B12 deficiency, and pernicious anemia. The following directions may be popular for future research: (1) The role of Helicobacter pylori in the pathogenesis of AIG; (2) diagnostic criteria for AIG and reference values for serum antibodies; (3) comorbidity mechanisms between AIG and other autoimmune diseases; (4) specific risks of AIG complicating gastric and other cancers; and (5) the role of vitamin B12 supplementation in patients with early-stage AIG. CONCLUSION This bibliometric analysis reported on popular topics and emerging trends in AIG, with diagnosis and prognosis being research hotspots in this field.
Collapse
Affiliation(s)
- Yun-Feng Yu
- The First Hospital, Hunan University of Chinese Medicine, Changsha 410007, Hunan Province, China
| | - Ke-Ke Tong
- The Hospital of Hunan University of Traditional Chinese Medicine, Hunan University of Traditional Chinese Medicine, Changde 415213, Hunan Province, China
| | - Xue-Li Shangguan
- The First Hospital, Hunan University of Chinese Medicine, Changsha 410007, Hunan Province, China
| | - Xin-Yu Yang
- College of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, Hunan Province, China
| | - Jing-Yi Wu
- The Third Hospital, Zhejiang Chinese Medical University, Hangzhou 310005, Zhejiang Province, China
| | - Gang Hu
- The First Hospital, Hunan University of Chinese Medicine, Changsha 410007, Hunan Province, China
| | - Rong Yu
- The First Hospital, Hunan University of Chinese Medicine, Changsha 410007, Hunan Province, China
| | - Chuan-Chuan Tan
- The First Hospital, Hunan University of Chinese Medicine, Changsha 410007, Hunan Province, China
| |
Collapse
|
|
30
|
Alshamrani S, Mashraqi MM, Alzamami A, Alturki NA, Almasoudi HH, Alshahrani MA, Basharat Z. Mining Autoimmune-Disorder-Linked Molecular-Mimicry Candidates in Clostridioides difficile and Prospects of Mimic-Based Vaccine Design: An In Silico Approach. Microorganisms 2023; 11:2300. [PMID: 37764144 PMCID: PMC10536613 DOI: 10.3390/microorganisms11092300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 09/07/2023] [Accepted: 09/07/2023] [Indexed: 09/29/2023] Open
Abstract
Molecular mimicry, a phenomenon in which microbial or environmental antigens resemble host antigens, has been proposed as a potential trigger for autoimmune responses. In this study, we employed a bioinformatics approach to investigate the role of molecular mimicry in Clostridioides difficile-caused infections and the induction of autoimmune disorders due to this phenomenon. Comparing proteomes of host and pathogen, we identified 23 proteins that exhibited significant sequence homology and were linked to autoimmune disorders. The disorders included rheumatoid arthritis, psoriasis, Alzheimer's disease, etc., while infections included viral and bacterial infections like HIV, HCV, and tuberculosis. The structure of the homologous proteins was superposed, and RMSD was calculated to find the maximum deviation, while accounting for rigid and flexible regions. Two sequence mimics (antigenic, non-allergenic, and immunogenic) of ≥10 amino acids from these proteins were used to design a vaccine construct to explore the possibility of eliciting an immune response. Docking analysis of the top vaccine construct C2 showed favorable interactions with HLA and TLR-4 receptor, indicating potential efficacy. The B-cell and T-helper cell activity was also simulated, showing promising results for effective immunization against C. difficile infections. This study highlights the potential of C. difficile to trigger autoimmunity through molecular mimicry and vaccine design based on sequence mimics that trigger a defensive response.
Collapse
Affiliation(s)
- Saleh Alshamrani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia; (S.A.); (H.H.A.); (M.A.A.)
| | - Mutaib M. Mashraqi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia; (S.A.); (H.H.A.); (M.A.A.)
| | - Ahmad Alzamami
- Clinical Laboratory Science Department, College of Applied Medical Science, Shaqra University, AlQuwayiyah 11961, Saudi Arabia;
| | - Norah A. Alturki
- Clinical Laboratory Science Department, College of Applied Medical Science, King Saud University, Riyadh 11433, Saudi Arabia;
| | - Hassan H. Almasoudi
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia; (S.A.); (H.H.A.); (M.A.A.)
| | - Mohammed Abdulrahman Alshahrani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran 61441, Saudi Arabia; (S.A.); (H.H.A.); (M.A.A.)
| | | |
Collapse
|
|
31
|
Ihara T, Ihara N, Kushima R, Haruma K. Rapid Progression of Autoimmune Gastritis after Helicobacter pylori Eradication Therapy. Intern Med 2023; 62:1603-1609. [PMID: 36261377 PMCID: PMC10292996 DOI: 10.2169/internalmedicine.0533-22] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 09/04/2022] [Indexed: 04/07/2023] Open
Abstract
We herein report a case of autoimmune gastritis (AIG) with rapid progression after Helicobacter pylori eradication therapy. The patient's previous gastritis had followed the course of type B gastritis before eradication therapy for many years. Immediately after eradication, we diagnosed her with AIG and carefully followed changes in the endoscopic and histopathological findings and serum markers. All of these clinical findings showed significant atrophic progression in the corporal area for approximately three years. We concluded that H. pylori eradication therapy exacerbated AIG in this case.
Collapse
Affiliation(s)
| | | | - Ryoji Kushima
- Department of Pathology, Shiga University of Medical Science, Japan
| | - Ken Haruma
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Japan
| |
Collapse
|
|
32
|
Abstract
Autoimmune gastritis (AIG) typically exhibits the characteristics of type A gastritis and has been classified as a separate disease from type B gastritis that corresponds to Helicobacter pylori gastritis. However, many reports have suggested the involvement of H. pylori infection in the pathogenesis of AIG. In our two cases, the patients' previous gastritis exhibited a clear pattern in which H. pylori gastritis had progressed over many years, but ultimately transitioned to AIG with its spontaneous disappearance. These findings suggest that some cases of AIG might originate from long-standing H. pylori gastritis.
Collapse
Affiliation(s)
| | | | - Ryoji Kushima
- Department of Pathology, Shiga University of Medical Science, Japan
| |
Collapse
|
|
33
|
Kotera T, Nishimi Y, Kushima R, Haruma K. Regression of Autoimmune Gastritis after Eradication of Helicobacter pylori. Case Rep Gastroenterol 2023; 17:34-40. [PMID: 36742095 PMCID: PMC9894002 DOI: 10.1159/000528388] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2022] [Accepted: 11/17/2022] [Indexed: 01/11/2023] Open
Abstract
We report a case of autoimmune gastritis (AIG) in which gastric mucosal atrophy improved with Helicobacter pylori eradication. Based on endoscopic findings (advanced gastric atrophy with vascular visibility and diffuse redness in remnant oxyntic mucosa), a woman in her 40s was suspected of having AIG coexisting with an active H. pylori infection. This was confirmed by a positive anti-parietal cell antibody (PCA, 1:160), an elevated serum gastrin level (638 pg/mL), and positive anti-H. pylori antibody (Hp Ab, 15.5 U/mL) and H. pylori stool antigen tests. Seven months after eradication, reduced vascular visibility and disappearance of diffuse redness on endoscopy and reduced PCA (1:40) and Hp Ab (5.1 U/mL) titers were observed, although histopathological findings (basal-predominant lymphocytic infiltration, destruction of parietal and chief cells, pseudopyloric metaplasia, and enterochromaffin-like cell hyperplasia) were consistent with AIG. Endoscopy 26 months after eradication showed further improvement in atrophic findings in the gastric corpus and histopathological recovery of parietal and chief cells in fundic glands. Serum gastrin levels returned to normal (64 pg/mL), and the PCA titer fell further (1:20).
Collapse
Affiliation(s)
- Tohru Kotera
- Department of Medical Examination, Uji-Tokushukai Medical Center, Uji, Japan
| | - Yurika Nishimi
- Department of Emergency and General Medicine, Uji-Tokushukai Medical Center, Uji, Japan
| | - Ryoji Kushima
- Department of Pathology, Shiga University of Medical Science, Otsu, Japan
| | - Ken Haruma
- Department of General Internal Medicine 2, Kawasaki Medical School General Medical Center, Okayama, Japan
| |
Collapse
|
|
34
|
Krick D, Hauptmann K, Penndorf V, Tacke F, Krüger R, von Bernuth H, Sigal M. When malignancy hits twice – synchronous gastric carcinoma and non-Hodgkin-B-cell lymphoma in a patient with common variable immunodeficiency. ZEITSCHRIFT FÜR GASTROENTEROLOGIE 2022. [PMID: 36413990 DOI: 10.1055/a-1890-6140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
AbstractPatients with common variable immunodeficiency (CVID) generally bear a higher risk of non Hodgkin B-cell lymphomas and solid tumors, in particular gastric adenocarcinoma.Here we report a case of a 58-year-old male CVID patient who developed both malignancies within a very short period, as documented by two subsequent esophagogastroduodenoscopies performed within 4 months. While the first upper gastrointestinal endoscopy for routine surveillance purposes was uneventful, the second one after developing unexplained weight loss revealed two new neoplastic lesions in the stomach. The histological evaluation revealed a poorly differentiated adenocarcinoma infiltrating the muscularis propria forcing gastrectomy as well as a high-grade B-non-Hodgkin-lymphoma with detection of a MYC- and BCL6-translocation, necessitating chemotherapy with R-CHOP.This case emphasizes the necessity of high awareness for gastric neoplasia in patients with CVID and highlights the need of a standardized yet not established endoscopic surveillance protocol for this vulnerable group.
Collapse
Affiliation(s)
- David Krick
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Kathrin Hauptmann
- Institute of Pathology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Volker Penndorf
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Frank Tacke
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Renate Krüger
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Horst von Bernuth
- Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - Michael Sigal
- Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Berlin, Germany
| |
Collapse
|
|
35
|
Takeuchi H, Okamoto A. Helicobacter pylori Infection and Chronic Immune Thrombocytopenia. J Clin Med 2022; 11:jcm11164822. [PMID: 36013059 PMCID: PMC9410305 DOI: 10.3390/jcm11164822] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 08/15/2022] [Accepted: 08/15/2022] [Indexed: 12/13/2022] Open
Abstract
Approximately half of the world’s population is infected with Helicobacter pylori, which causes gastric disease. Recent systematic reviews and meta-analyses have reported that H. pylori may also have extragastric manifestations such as hematologic diseases, including chronic immune thrombocytopenia (cITP). However, the molecular mechanisms by which H. pylori induces cITP remain unclear, and may involve the host immune response, bacterial strain diversity, and delivery of bacterial molecules to the host blood vessels. This review discusses the important pathophysiological mechanisms by which H. pylori potentially contributes to the development of cITP in infected patients.
Collapse
|
|
36
|
Zingone F, Pilotto V, Cardin R, Maddalo G, Orlando C, Fassan M, Marsilio I, Collesei E, Pelizzaro F, Farinati F. Autoimmune Atrophic Gastritis: The Role of miRNA in Relation to Helicobacter Pylori Infection. Front Immunol 2022; 13:930989. [PMID: 35941891 PMCID: PMC9356369 DOI: 10.3389/fimmu.2022.930989] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Accepted: 06/23/2022] [Indexed: 12/14/2022] Open
Abstract
INTRODUCTION MicroRNAs (miRNAs) have been proposed as diagnostic markers, biomarkers of neoplastic progression, and possible therapeutic targets in several immune-mediated diseases. We aimed to analyze the expression profile of selected miRNAs (miR21, miR142, miR223, miR155) in patients with autoimmune atrophic gastritis (AAG), patients with non-autoimmune multifocal atrophic gastritis (MAG), and healthy control subjects (HC). MATERIALS AND METHODS A total of 103 patients with AAG were consecutively recruited for this study among those attending our gastroenterology outpatient clinic. Participating patients were divided into two groups: primary, not Helicobacter pylori (HP)-associated related AAG (n=57, P-AAG) and HP-associated AAG (n=46, HP-AAG); this subgroup included HP-positive patients, patients with previously reported HP infection, and patients harboring antral atrophy, considered as a stigma of HP infection. We also included 20 sex-age-matched MAG patients and 10 HC. Upper endoscopy with gastric biopsies were performed on each AAG and MAG patient. Circulating levels of miR21-5p, miR142-3p, miR223-3p, and miR155-5p were measured by RT-PCR in all groups. RESULTS MiR-21 was over-expressed in P-AAG (p=0.02), HP-AAG (p = 0.04), and MAG (p=0.03) compared with HC. By contrast, miR-142 was more expressed in HC than in HP-AAG (p=0.04) and MAG (p=0.03). MiR-155 showed no significant differences among the four subgroups, while, unexpectedly, miR-223 was overexpressed in HC compared to P-AAG (p=0.01), HP-AAG (p=0.003), and MAG (p<0.001), and was higher in P-AAG than in MAG (p=0.05). CONCLUSIONS MiR-21 was over-expressed in patients with gastric precancerous conditions irrespective of etiology, while in the same subgroups miR-142 and miR-223 were under-expressed compared to healthy controls. Controlling miRNAs up- or downregulation could lead to a breakthrough in treating chronic autoimmune diseases and potentially interfere with the progression to cancer.
Collapse
Affiliation(s)
- Fabiana Zingone
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale Università -Padova, Padua, Italy
| | - Valentina Pilotto
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale Università -Padova, Padua, Italy
| | - Romilda Cardin
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Gemma Maddalo
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale Università -Padova, Padua, Italy
| | - Costanza Orlando
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale Università -Padova, Padua, Italy
| | - Matteo Fassan
- Department of Medicine, Surgical Pathology Unit, University of Padua, Padua, Italy
- Veneto Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Padua, Italy
| | - Ilaria Marsilio
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Eugenio Collesei
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
| | - Filippo Pelizzaro
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale Università -Padova, Padua, Italy
| | - Fabio Farinati
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy
- Gastroenterology Unit, Azienda Ospedale Università -Padova, Padua, Italy
| |
Collapse
|
|
37
|
Endoscopic Features of Autoimmune Gastritis: Focus on Typical Images and Early Images. J Clin Med 2022; 11:jcm11123523. [PMID: 35743593 PMCID: PMC9224887 DOI: 10.3390/jcm11123523] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 06/15/2022] [Accepted: 06/16/2022] [Indexed: 02/01/2023] Open
Abstract
Autoimmune gastritis (AIG) is chronic atrophic gastritis caused by an autoimmune mechanism of unknown etiology and presents with various pathological conditions by causing an achlorhydria state through parietal cell damage. The most characteristic endoscopic finding in AIG is advanced corpus-dominant mucosal atrophy. A recent study that examined several cases in Japan revealed the presence of endoscopic features other than corpus-dominant advanced atrophy. Remnants of oxyntic mucosa and sticky adherent dense mucus were found in ≥30% of cases, and hyperplastic polyps were found in ≥20% of cases. In image-enhanced endoscopy (IEE), white globe appearance (WGA) was observed in 32% of AIG cases. Additionally, some reports have stated that the findings in AIG cases using IEE showed cast-off skin appearance (CSA) and foveola type mucosa; however, a consensus is yet to be achieved. These endoscopic results were found in cases of advanced-stage AIG. There have been few reports concerning early-stage AIG cases. In these few reports, all of the cases were pathologically diagnosed as early AIG. In all of the cases, the pathological findings almost always showed neither parietal cell destruction nor atrophy. Endoscopic findings such as “mosaic pattern with slight swelling of the areae gastricae”, “diffuse reddened and edematous gastric fundic gland mucosa”, and “pseudopolyp-like nodules” may be common characteristics of early images. In such early cases, high antibody titers, no atrophic changes, and few clinical abnormal findings were shown. Endoscopists are expected to update their knowledge regarding AIG diagnosis with the evolution of imaging equipment.
Collapse
|
|
38
|
Kamada T, Maruyama Y, Monobe Y, Haruma K. Endoscopic features and clinical importance of autoimmune gastritis. Dig Endosc 2022; 34:700-713. [PMID: 34674318 DOI: 10.1111/den.14175] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 10/19/2021] [Accepted: 10/19/2021] [Indexed: 12/13/2022]
Abstract
Autoimmune gastritis (AIG) is a special type of chronic gastritis characterized by autoimmune disorders caused by cellular immunity, resulting in the destruction of parietal cells and production of antiparietal cell antibodies. Endoscopic findings of AIG are mainly characterized by corpus-dominant advanced atrophy. The antral area is generally considered to have no or mild atrophy; however, there are cases wherein the gastric mucosa is red or faded due to past infection with Helicobacter pylori or bile reflux. Currently, there are no diagnostic criteria for AIG in Japan, and it is important to make a diagnosis based on the presence of gastric autoantibodies and characteristic endoscopic and histological findings. AIG is associated with gastric cancer, neuroendocrine tumors (NETs), and other autoimmune diseases, such as thyroid diseases, anemia, and neurological symptoms due to impaired absorption of iron and vitamin B12 , and thus requires systemic treatment. The significance of diagnosing AIG is to include patients as a high-risk group for the development of gastric cancer and gastric NETs, provide an opportunity to detect autoimmune endocrine diseases, and initiate therapeutic intervention before anemia and neurological symptoms develop. It is important to pay close attention to the occurrence of AIG comorbidities not only at the time of AIG diagnosis but also during follow-up after detection.
Collapse
Affiliation(s)
- Tomoari Kamada
- Department of, Health Care Medicine, Kawasaki Medical School, Okayama, Japan
| | - Yasuhiko Maruyama
- Department of Gastroenterology, Fujieda Municipal General Hospital, Shizuoka, Japan
| | - Yasumasa Monobe
- Department of, Pathology, Kawasaki Medical School, Okayama, Japan
| | - Ken Haruma
- Department of, General Internal Medicine 2, Kawasaki Medical School, Okayama, Japan
| |
Collapse
|
|
39
|
Garabatos N, Santamaria P. Gut Microbial Antigenic Mimicry in Autoimmunity. Front Immunol 2022; 13:873607. [PMID: 35572569 PMCID: PMC9094498 DOI: 10.3389/fimmu.2022.873607] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 03/14/2022] [Indexed: 12/12/2022] Open
Abstract
The gut microbiota plays a major role in the developmental biology and homeostasis of cells belonging to the adaptive and innate arms of the immune system. Alterations in its composition, which are known to be regulated by both genetic and environmental factors, can either promote or suppress the pathogenic processes underlying the development of various autoimmune diseases, including inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, type 1 diabetes and rheumatoid arthritis, to just name a few. Cross-recognition of gut microbial antigens by autoreactive T cells as well as gut microbe-driven alterations in the activation and homeostasis of effector and regulatory T cells have been implicated in this process. Here, we summarize our current understanding of the positive and negative associations between alterations in the composition of the gut microbiota and the development of various autoimmune disorders, with a special emphasis on antigenic mimicry.
Collapse
Affiliation(s)
- Nahir Garabatos
- Institut D'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
| | - Pere Santamaria
- Institut D'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain
- Julia McFarlane Diabetes Research Centre (JMDRC), Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| |
Collapse
|
|
40
|
Esposito G, Dottori L, Pivetta G, Ligato I, Dilaghi E, Lahner E. Pernicious Anemia: The Hematological Presentation of a Multifaceted Disorder Caused by Cobalamin Deficiency. Nutrients 2022; 14:nu14081672. [PMID: 35458234 PMCID: PMC9030741 DOI: 10.3390/nu14081672] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 04/08/2022] [Accepted: 04/14/2022] [Indexed: 02/04/2023] Open
Abstract
Pernicious anemia is still a neglected disorder in many medical contexts and is underdiagnosed in many patients. Pernicious anemia is linked to but different from autoimmune gastritis. Pernicious anemia occurs in a later stage of autoimmune atrophic gastritis when gastric intrinsic factor deficiency and consequent vitamin B12 deficiency may occur. The multifaceted nature of pernicious anemia is related to the important role of cobalamin, which, when deficient, may lead to several dysfunctions, and thus, the proteiform clinical presentations of pernicious anemia. Indeed, pernicious anemia may lead to potentially serious long-term complications related to micronutrient deficiencies and their consequences and the development of gastric cancer and type 1 gastric neuroendocrine tumors. When not recognized in a timely manner or when pernicious anemia is diagnosed with delay, these complications may be potentially life-threatening and sometimes irreversible. The current review aimed to focus on epidemiology, pathogenesis, and clinical presentations of pernicious anemia in an attempt to look beyond borders of medical specialties. It aimed to focus on micronutrient deficiencies besides the well-known vitamin B12 deficiency, the diagnostic approach for pernicious anemia, its long-term complications and optimal clinical management, and endoscopic surveillance of patients with pernicious anemia.
Collapse
|
|
41
|
Wang L, Cao ZM, Zhang LL, Dai XC, Liu ZJ, Zeng YX, Li XY, Wu QJ, Lv WL. Helicobacter Pylori and Autoimmune Diseases: Involving Multiple Systems. Front Immunol 2022; 13:833424. [PMID: 35222423 PMCID: PMC8866759 DOI: 10.3389/fimmu.2022.833424] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 01/24/2022] [Indexed: 12/12/2022] Open
Abstract
The modern Gastroenterology have witnessed an essential stride since Helicobacter pylori was first found in the stomach and then its pathogenic effect was discovered. According to the researches conducted during the nearly 40 years, it has been found that this bacterium is associated with a natural history of many upper gastrointestinal diseases. Epidemiological data show an increased incidence of autoimmune disorders with or after infection with specific microorganisms. The researches have revealed that H. pylori is a potential trigger of gastric autoimmunity, and it may be associated with other autoimmune diseases, both innate and acquired. This paper reviews the current support or opposition about H. pylori as the role of potential triggers of autoimmune diseases, including inflammatory bowel disease, autoimmune thyroiditis, type 1 diabetes mellitus, autoimmune liver diseases, rheumatoid arthritis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, as well as Sjogren’s syndrome, chronic urticaria and psoriasis, and tried to explain the possible mechanisms.
Collapse
Affiliation(s)
- Li Wang
- Department of Infection, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zheng-Min Cao
- Department of Infection, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Li-Li Zhang
- Department of Infection, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xin-Can Dai
- Department of Infection, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Zhen-Ju Liu
- Department of Proctology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yi-Xian Zeng
- Department of Proctology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xin-Ye Li
- Department of Cardiovascular, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qing-Juan Wu
- Department of Infection, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Wen-Liang Lv
- Department of Infection, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| |
Collapse
|
|
42
|
An H, Eun M, Yi J, Park J. CRESSP: a comprehensive pipeline for prediction of immunopathogenic SARS-CoV-2 epitopes using structural properties of proteins. Brief Bioinform 2022; 23:6539139. [PMID: 35226074 DOI: 10.1093/bib/bbac056] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 01/04/2022] [Accepted: 02/03/2022] [Indexed: 12/16/2022] Open
Abstract
The development of autoimmune diseases following SARS-CoV-2 infection, including multisystem inflammatory syndrome, has been reported, and several mechanisms have been suggested, including molecular mimicry. We developed a scalable, comparative immunoinformatics pipeline called cross-reactive-epitope-search-using-structural-properties-of-proteins (CRESSP) to identify cross-reactive epitopes between a collection of SARS-CoV-2 proteomes and the human proteome using the structural properties of the proteins. Overall, by searching 4 911 245 proteins from 196 352 SARS-CoV-2 genomes, we identified 133 and 648 human proteins harboring potential cross-reactive B-cell and CD8+ T-cell epitopes, respectively. To demonstrate the robustness of our pipeline, we predicted the cross-reactive epitopes of coronavirus spike proteins, which were recognized by known cross-neutralizing antibodies. Using single-cell expression data, we identified PARP14 as a potential target of intermolecular epitope spreading between the virus and human proteins. Finally, we developed a web application (https://ahs2202.github.io/3M/) to interactively visualize our results. We also made our pipeline available as an open-source CRESSP package (https://pypi.org/project/cressp/), which can analyze any two proteomes of interest to identify potentially cross-reactive epitopes between the proteomes. Overall, our immunoinformatic resources provide a foundation for the investigation of molecular mimicry in the pathogenesis of autoimmune and chronic inflammatory diseases following COVID-19.
Collapse
Affiliation(s)
- Hyunsu An
- School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Republic of Korea
| | - Minho Eun
- School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Republic of Korea
| | - Jawoon Yi
- School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Republic of Korea
| | - Jihwan Park
- School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Republic of Korea.,Anti-Virus Research Center, Gwangju Institute of Science and Technology (GIST), Republic of Korea.,Laboratory for cell mechanobiology, Gwangju Institute of Science and Technology (GIST), Republic of Korea
| |
Collapse
|
|
43
|
Abstract
Purpose of Review Gastric neuroendocrine neoplasms (g-NENs) are a rare type of stomach cancer. The three main subtypes have different pathogeneses, biological behaviours and clinical characteristics, so they require different management strategies. This article will provide an overview of g-NENs and highlight recent advances in the field. Recent Findings Molecular profiling has revealed differences between indolent and aggressive g-NENs, as well as a new somatic mutation responsible for some familial type I g-NENs. Novel biomarkers have been developed which will hopefully improve diagnosis, treatment, risk stratification and follow-up. Patient treatment is also changing, as evidence supports the use of less aggressive options (e.g. endoscopic surveillance or resection) in some patients with more indolent tumours. Summary g-NEN heterogeneity poses challenges in understanding and managing this rare disease. More basic science research is needed to investigate molecular pathogenesis, and future larger clinical studies will hopefully also further improve treatment and patient outcomes.
Collapse
|
|
44
|
Das S. Frank conjunctival bleeding in a male patient – A very rare presentation. MEDICAL JOURNAL OF DR. D.Y. PATIL VIDYAPEETH 2022. [DOI: 10.4103/mjdrdypu.mjdrdypu_275_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
|
|
45
|
Hoft SG, Noto CN, DiPaolo RJ. Two Distinct Etiologies of Gastric Cancer: Infection and Autoimmunity. Front Cell Dev Biol 2021; 9:752346. [PMID: 34900999 PMCID: PMC8661534 DOI: 10.3389/fcell.2021.752346] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 11/12/2021] [Indexed: 12/14/2022] Open
Abstract
Gastric cancer is a leading cause of mortality worldwide. The risk of developing gastric adenocarcinoma, which comprises >90% of gastric cancers, is multifactorial, but most associated with Helicobacter pylori infection. Autoimmune gastritis is a chronic autoinflammatory syndrome where self-reactive immune cells are activated by gastric epithelial cell autoantigens. This cause of gastritis is more so associated with the development of neuroendocrine tumors. However, in both autoimmune and infection-induced gastritis, high risk metaplastic lesions develop within the gastric mucosa. This warrants concern for carcinogenesis in both inflammatory settings. There are many similarities and differences in disease progression between these two etiologies of chronic gastritis. Both diseases have an increased risk of gastric adenocarcinoma development, but each have their own unique comorbidities. Autoimmune gastritis is a primary cause of pernicious anemia, whereas chronic infection typically causes gastrointestinal ulceration. Both immune responses are driven by T cells, primarily CD4+ T cells of the IFN-γ producing, Th1 phenotype. Neutrophilic infiltrates help clear H. pylori infection, but neutrophils are not necessarily recruited in the autoimmune setting. There have also been hypotheses that infection with H. pylori initiates autoimmune gastritis, but the literature is far from definitive with evidence of infection-independent autoimmune gastric disease. Gastric cancer incidence is increasing among young women in the United States, a population at higher risk of developing autoimmune disease, and H. pylori infection rates are falling. Therefore, a better understanding of these two chronic inflammatory diseases is needed to identify their roles in initiating gastric cancer.
Collapse
Affiliation(s)
- Stella G Hoft
- Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, United States
| | - Christine N Noto
- Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, United States
| | - Richard J DiPaolo
- Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, United States
| |
Collapse
|
|
46
|
Sarsenbaeva AS. <i>Helicobacter pylori</i>-associated comorbidity. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2021:38-52. [DOI: 10.31146/1682-8658-ecg-193-9-38-52] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Abstract
Helicobacter pylori (H. pylori) infection is known to lead to various diseases such as gastric and duodenal ulcers, chronic gastritis and malignant diseases, including MALT lymphoma and stomach cancer. To date, various factors of pathogenicity and virulence of the H. pylori bacterium have been studied. The interaction of infection with host cells leads to the induction of inflammatory responses through the release of cytokines, activation of apoptosis or proliferation, which leads to inflammation and dysfunction of the epithelial barrier. This process can facilitate the movement of H. pylori virulence factors and inflammatory mediators into the bloodstream and promote or enhance the development of a systemic inflammatory response and the possible clinical effects of H. pylori infections outside the stomach. The purpose of this review is to clarify the available data on H. pylori-associated comorbidity with diseases of the cardiovascular, nervous, endocrine systems, autoimmune diseases and some other pathologies outside the digestive system.
Collapse
Affiliation(s)
- A. S. Sarsenbaeva
- South Ural State Medical University of the Ministry of Health of the Russian Federation
| |
Collapse
|
|
47
|
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.
Collapse
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.
| |
Collapse
|
|
48
|
Kitamura S, Muguruma N, Okamoto K, Kagemoto K, Kida Y, Mitsui Y, Ueda H, Kawaguchi T, Miyamoto H, Sato Y, Aoki R, Shunto J, Bando Y, Takayama T. Clinicopathological characteristics of early gastric cancer associated with autoimmune gastritis. JGH Open 2021; 5:1210-1215. [PMID: 34622010 PMCID: PMC8485395 DOI: 10.1002/jgh3.12656] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Revised: 08/25/2021] [Accepted: 09/03/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Autoimmune gastritis is known to be associated with neoplastic lesions but the relationship between autoimmunity and tumorigenesis have not been sufficiently clarified. The aim of this study is to assess the clinicopathological characteristics of gastric cancer cases associated with autoimmune gastritis. METHODS A total of 24 patients diagnosed as early gastric cancer with autoimmune gastritis were registered. Chart reviews with the data including age, gender, state of Helicobacter pylori infection, comorbidity, and concomitant gastric diseases were conducted. As for the characteristics of gastric cancer, location, size, morphological type, histopathology, invasion depth, and the presence of metachronous or simultaneous lesion were assessed. These data from autoimmune gastritis group were compared with those from 301 patients of early gastric cancer as a control group. RESULTS The gastric cancer associated with autoimmune gastritis was located in the upper, middle, and lower parts in 28.1%, 53.1%, and 18.8%, respectively. The morphological types are as follows: 0-I, 9.4%; 0-IIa, 28.1%; 0-IIb, 15.6%; 0-IIc, 46.9%; and 0-III, 0.0%. The mean tumor size was 21.8 mm. While 90.6% were confined to the mucosa, 9.4% showed submucosal invasion. The histological classifications are as follows: tub1, 50.0%; tub2, 15.6%; pap, 21.9%; sig, 9.4%; and por, 3.1%. More numbers of female, protruded types, larger tumor size, papillary tumor, and that in the upper location were observed in autoimmune gastritis group compared to control group. CONCLUSION Early gastric cancer associated with autoimmune gastritis demonstrated different characteristics from those without autoimmune gastritis including variety of tumor morphologies and histological types with female dominancy.
Collapse
Affiliation(s)
| | - Naoki Muguruma
- Department of Gastroenterology and OncologyTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Koichi Okamoto
- Department of Gastroenterology and OncologyTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Kaizo Kagemoto
- Department of Gastroenterology and OncologyTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Yoshifumi Kida
- Department of Gastroenterology and OncologyTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Yasuhiro Mitsui
- Department of Gastroenterology and OncologyTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Hiroyuki Ueda
- Department of Gastroenterology and OncologyTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Tomoyuki Kawaguchi
- Department of Gastroenterology and OncologyTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Hiroshi Miyamoto
- Department of Gastroenterology and OncologyTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Yasushi Sato
- Department of Gastroenterology and OncologyTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| | - Rika Aoki
- Tokushima Health Screening CenterTokushimaJapan
| | | | - Yoshimi Bando
- Division of PathologyTokushima University HospitalTokushimaJapan
| | - Tetsuji Takayama
- Department of Gastroenterology and OncologyTokushima University Graduate School of Biomedical SciencesTokushimaJapan
| |
Collapse
|
|
49
|
Rustgi SD, Bijlani P, Shah SC. Autoimmune gastritis, with or without pernicious anemia: epidemiology, risk factors, and clinical management. Therap Adv Gastroenterol 2021; 14:17562848211038771. [PMID: 34484423 PMCID: PMC8414617 DOI: 10.1177/17562848211038771] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 07/22/2021] [Indexed: 02/04/2023] Open
Abstract
Autoimmune gastritis (AIG) is a chronic immune-mediated, inflammatory condition that involves the destruction of the gastric oxyntic mucosa through the autoimmune-mediated loss of parietal cells, with replacement by atrophic and metaplastic tissue. Diagnosing AIG is important, given the need for ongoing clinical management and vigilance with respect to downstream complications, the most serious of which is gastric adenocarcinoma. Other clinical consequences include gastric neuroendocrine tumors, consequences related to decreased gastric acid and decreased intrinsic factor due to parietal cell destruction and antibodies against intrinsic factor (e.g. micronutrient deficiencies), as well as concomitant autoimmune disorders. Considering the prevalence of AIG and the potential for severe clinical outcomes, it is important to engage in efforts to reduce practice pattern variability related to diagnosis and management. Accordingly, herein, we review of the epidemiology, pathogenesis, clinical presentation of AIG, including both gastric and extragastric manifestations, and provide an overview of clinical management.
Collapse
Affiliation(s)
- Sheila D Rustgi
- Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; Division of Digestive and Liver Diseases, Columbia University Irving Medical Center, New York, NY, USA
| | - Priyesha Bijlani
- Department of Medicine, University of California, San Diego, La Jolla, CA, USA
| | - Shailja C Shah
- Section of Gastroenterology, VA San Diego Healthcare System, 3350 La Jolla Villa Drive, San Diego, CA 92161, USA
| |
Collapse
|
|
50
|
Nishizawa T, Yoshida S, Watanabe H, Toyoshima A, Kataoka Y, Takahashi Y, Kanazawa T, Ebinuma H, Suzuki H, Koike K, Toyoshima O. Clue of Diagnosis for Autoimmune Gastritis. Digestion 2021; 102:903-910. [PMID: 34198294 DOI: 10.1159/000516624] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 04/18/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND The diagnostic clues for autoimmune gastritis (AIG) can be classified into 2 categories: endoscopic findings and pathological diagnosis. We believe that research on the AIG detection rate by endoscopists could provide a better understanding of the diagnosis of AIG. This study aimed to clarify the ratio of the endoscopic and the pathological diagnoses of AIG. METHODS We retrospectively reviewed consecutive patients who underwent esophagogastroduodenoscopy (EGD). During their first EGD, the gastric mucosa with C2 atrophy or more was biopsied for pathological evaluation based on the updated Sydney system. A gastric biopsy was also performed after Helicobacter pylori eradication, obtaining specimens from at least 2 sites, the greater curvature of the corpus and the antrum. We enrolled patients who were positive for the anti-parietal cell antibody and were diagnosed with AIG, histologically and/or endoscopically. The detection rates of AIG were compared between endoscopic diagnosis and pathological diagnosis. RESULTS A total of 10,822 patients underwent EGD during the study period. Finally, 41 patients with AIG were enrolled, leading to an AIG prevalence of 0.38% in this study. As for the clue leading to AIG detection, 31.7% (13/41) were diagnosed through endoscopy (proximal-predominant atrophy), and 68.3% (28/41) were diagnosed pathologically. The AIG detection rate by endoscopists in the posteradication group was significantly lower than in the H. pylori-negative group (p < 0.05). CONCLUSION Endoscopists frequently overlooked AIG, especially in posteradication cases. Pathological assessment using the updated Sydney system after H. pylori eradication might be a promising strategy to detect AIG better.
Collapse
Affiliation(s)
- Toshihiro Nishizawa
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology and Hepatology, International University of Health and Welfare Narita Hospital, Chiba, Japan
| | - Shuntaro Yoshida
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | | | - Akira Toyoshima
- Department of Colorectal Surgery, Japanese Red Cross Medical Center, Tokyo, Japan
| | - Yosuke Kataoka
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | | | - Takamitsu Kanazawa
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastrointestinal Surgery, JR Tokyo General Hospital, Tokyo, Japan
| | - Hirotoshi Ebinuma
- Department of Gastroenterology and Hepatology, International University of Health and Welfare Narita Hospital, Chiba, Japan
| | - Hidekazu Suzuki
- Department of Gastroenterology and Hepatology, Tokai University School of Medicine, Isehara city, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | | |
Collapse
|