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Mohamed MA, Mahmoud EA, Basily MS, Mohamed MM, Ahmed OAA, Abdelkreem E. Efficacy of treating Helicobacter pylori infection on seizure frequency in children with drug-resistant idiopathic generalized epilepsy: a randomized controlled trial. Ital J Pediatr 2025; 51:121. [PMID: 40247384 PMCID: PMC12004564 DOI: 10.1186/s13052-025-01956-2] [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: 10/02/2024] [Accepted: 03/27/2025] [Indexed: 04/19/2025] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) causes chronic infection in more than half of the population worldwide. Accumulating body of evidence indicates the possible role of H. Pylori infection in extra-intestinal health problems, including epilepsy. This study aims to investigate the efficacy of treating H. pylori infection on seizure frequency among children with drug-resistant idiopathic generalized epilepsy (IGE). METHODS A parallel, two-arm, open-label, randomized controlled trial was conducted on 126 children with drug-resistant IGE and positive H. pylori stool antigen test who were randomly assigned to study and comparison groups in 1.2:1 ratio. Only the study group received H. pylori eradication therapy (esomeprazole, amoxicillin, and clarithromycin) for two weeks. The primary outcome was seizure improvement (≥ 50% seizure frequency reduction compared with baseline) after 2.5 months. Secondary outcomes were occurrence of status epilepticus, escalation of antiseizure medication (ASMs), and adverse effects. Outcomes between the two groups were compared using Chi-square/Fisher exact tests on an intention-to-treat principle. Logistic regression analysis was performed to investigate possible effects of baseline variables on primary outcome. RESULTS Seizure improvement occurred in 23 (33%) children in the study group compared with seven (12%) children in the comparison group (Risk ratio [RR] 2.7, 95% confidence interval [CI]: 1.3-5.9; p 0.006). The study group had lower occurrence of status epilepticus (2.9% vs. 14%; RR 0.21, 95%CI: 0.05-0.93; p 0.042) and lesser need for ASMs escalation (4.4% vs. 19.3%; RR 0.23, 95%CI: 0.07-0.77; p 0.010). Adverse effects were more frequent among subjects in the study group, including nausea (15.9% vs. 10.5%) vomiting (8.7% vs. 3.5%), diarrhea (11.6% vs. 5.3%), and skin rash (4.4% vs. 1.8%), but the differences were not statistically significant (p > 0.05). None of baseline participants' variables was significantly associated with the primary outcome. CONCLUSION Treating H. pylori infection may improve seizure control in children with drug-resistant IGE, but further studies are warranted to confirm our findings and explore mechanisms behind seizure improvement following H. pylori eradication therapy. TRIAL REGISTRATION Registered on www. CLINICALTRIALS gov (identifier: NCT05297695) on 17 March 2022. https://clinicaltrials.gov/study/NCT05297695 .
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Affiliation(s)
- Mostafa Ashry Mohamed
- Department of Pediatrics, Faculty of Medicine, Sohag University, Nasser City, Sohag, Egypt
| | - Ekram A Mahmoud
- Department of Medical Microbiology and Immunology, Faculty of Medicine, Sohag University, Nasser City, Sohag, Egypt
| | - Mina S Basily
- Department of Pediatrics, Faculty of Medicine, Sohag University, Nasser City, Sohag, Egypt
| | - Montaser M Mohamed
- Department of Pediatrics, Faculty of Medicine, Sohag University, Nasser City, Sohag, Egypt
| | - Omar A A Ahmed
- Department of Pediatrics, Faculty of Medicine, Sohag University, Nasser City, Sohag, Egypt
| | - Elsayed Abdelkreem
- Department of Pediatrics, Faculty of Medicine, Sohag University, Nasser City, Sohag, Egypt.
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Blank M, Israeli E, Halpert G, Cervera R. The Infectious Origin of the Anti-Phospholipid Syndrome. INFECTION AND AUTOIMMUNITY 2024:695-713. [DOI: 10.1016/b978-0-323-99130-8.00049-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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He J, Liu Y, Ouyang Q, Li R, Li J, Chen W, Hu W, He L, Bao Q, Li P, Hu C. Helicobacter pylori and unignorable extragastric diseases: Mechanism and implications. Front Microbiol 2022; 13:972777. [PMID: 35992650 PMCID: PMC9386483 DOI: 10.3389/fmicb.2022.972777] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Accepted: 07/11/2022] [Indexed: 11/15/2022] Open
Abstract
Considered as the most popular pathogen worldwide, Helicobacter pylori is intensively associated with diverse gastric diseases, including gastric ulcers, chronic progressive gastritis, and gastric cancer. Aside from its pathogenic effect on gastric diseases, growing evidences reveal that H. pylori may be related to numerous extragastric diseases. In this article, we reviewed recent studies and systematically elucidated that H. pylori may interfere with many biological processes outside the stomach and influence the occurrence of various extragastric diseases. Many epidemiological studies have indicated that H. pylori plays a pathogenic role in COVID-19, atherosclerosis, hyperemesis gravidarum and several other extragastric diseases, while the effect of H. pylori is currently under investigation in gastroesophageal reflux disease, asthma, and inflammatory bowel disease. Moreover, we also summarized the possible pathogenic mechanisms of H. pylori that may be related to chronic systemic inflammation and molecular mimicker. Taken together, this review provides a new perspective on the role of H. pylori in extragastric diseases and explores the possible mechanisms, which may help guide clinical treatment.
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Affiliation(s)
- Junjian He
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Yunyi Liu
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Qin Ouyang
- Department of Medicinal Chemistry, College of Pharmacy, Army Medical University, Chongqing, China
| | - Rongxing Li
- Department of Foreign Languages, Army Medical University, Chongqing, China
| | - Jie Li
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Weiyan Chen
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Weichao Hu
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Lijiao He
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Qiyu Bao
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Ping Li
- Institute of Cardiovascular Diseases, Xinqiao Hospital, Army Medical University, Chongqing, China
- *Correspondence: Ping Li,
| | - Changjiang Hu
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
- Changjiang Hu,
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Karbalaei M, Sahebkar A, Keikha M. Helicobacter pylori infection and susceptibility to cardiac syndrome X: A systematic review and meta-analysis. World J Meta-Anal 2021; 9:208-219. [DOI: 10.13105/wjma.v9.i2.208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 03/03/2021] [Accepted: 04/23/2021] [Indexed: 02/06/2023] Open
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Karbalaei M, Sahebkar A, Keikha M. Helicobacter pylori infection and susceptibility to cardiac syndrome X: A systematic review and meta-analysis. World J Meta-Anal 2021; 9:207-218. [DOI: 10.13105/wjma.v9.i2.207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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Mormile I, Granata F, Punziano A, de Paulis A, Rossi FW. Immunosuppressive Treatment in Antiphospholipid Syndrome: Is It Worth It? Biomedicines 2021; 9:biomedicines9020132. [PMID: 33535377 PMCID: PMC7911562 DOI: 10.3390/biomedicines9020132] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Revised: 01/18/2021] [Accepted: 01/26/2021] [Indexed: 11/16/2022] Open
Abstract
The antiphospholipid syndrome (APS) is characterized by the development of venous and/or arterial thrombosis and pregnancy morbidity in patients with persistent antiphospholipid antibodies (aPL). Catastrophic antiphospholipid syndrome (CAPS) is a life-threatening form of APS occurring in about 1% of cases. Lifelong anticoagulation with vitamin K antagonists remains the cornerstone of the therapy for thrombotic APS, but frequently the use of anticoagulation may be problematic due to the increased risk of bleeding, drug interactions, or comorbidities. Immunosuppressant drugs are widely used to treat several autoimmune conditions, in which their safety and effectiveness have been largely demonstrated. Similar evidence in the treatment of primary APS is limited to case reports or case series, and studies on a large scale lack. Immunomodulatory drugs may be an emerging tool in managing such particular situations, like refractory obstetrical complications, CAPS, or so-called APS non-criteria manifestations. In addition, immunomodulatory drugs may be useful in patients experiencing recurrent thromboembolic events despite optimized anticoagulant therapy. We did a comprehensive review of literature analyzing the possible role of immunomodulation in primary APS to provide a broad overview of potentially safe and effective target treatments for managing this devastating disease.
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Affiliation(s)
- Ilaria Mormile
- Department of Translational Medical Sciences, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy; (I.M.); (F.G.); (A.P.); (A.d.P.)
| | - Francescopaolo Granata
- Department of Translational Medical Sciences, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy; (I.M.); (F.G.); (A.P.); (A.d.P.)
| | - Alessandra Punziano
- Department of Translational Medical Sciences, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy; (I.M.); (F.G.); (A.P.); (A.d.P.)
| | - Amato de Paulis
- Department of Translational Medical Sciences, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy; (I.M.); (F.G.); (A.P.); (A.d.P.)
- Center for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, 80131 Naples, Italy
| | - Francesca Wanda Rossi
- Department of Translational Medical Sciences, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy; (I.M.); (F.G.); (A.P.); (A.d.P.)
- Center for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, 80131 Naples, Italy
- Correspondence: ; Tel.: +39-81-7464513
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Ponzetto A, Cavallo G, Figura N. Sudden Sensorineural Hearing Loss. JAMA Otolaryngol Head Neck Surg 2021; 146:211. [PMID: 31774477 DOI: 10.1001/jamaoto.2019.3662] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
Affiliation(s)
- Antonio Ponzetto
- Department of Medical Sciences, University of Torino Corso AM Dogliotti 14, 10126 Torino, Italy
| | - Giovanni Cavallo
- Division of Otorhynolaryngology, University of Turin, Hospital San Luigi Gonzaga, Regione Gonzole, Orbassano, Torino, Italy
| | - Natale Figura
- Department of Biotechnology Chemistry & Pharmacy, University of Siena, Siena, Italy
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Zheng K, Guo X, Yi F, Wang L, Mancuso A, Qi X. No Association between Ischemic Stroke and Portal Vein Thrombosis in Liver Cirrhosis. BIOMED RESEARCH INTERNATIONAL 2020; 2020:8172673. [PMID: 32714987 PMCID: PMC7352149 DOI: 10.1155/2020/8172673] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 05/17/2020] [Accepted: 06/11/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS There seems to be a higher risk of ischemic stroke and portal vein thrombosis in liver cirrhosis. Both of them may be associated with hypercoagulability. We aim to explore the association between ischemic stroke and portal vein thrombosis in liver cirrhosis. Study Design and Methods. We selected patients from our prospectively established database of liver cirrhosis from December 2014 to July 2019. The difference between patients with and without stroke was compared. A 1 : 1 propensity score matching (PSM) analysis was performed to adjust the effect of age, sex, Child-Pugh score, and MELD score on our statistical results. RESULTS There were 349 cirrhotic patients in the cross-sectional study. The prevalence of stroke, ischemic stroke, hemorrhagic stroke, and portal vein thrombosis was 8.88% (31/349), 8.31% (29/349), 1.15% (4/349), and 28.65% (100/349) in liver cirrhosis, respectively. Patients with ischemic stroke were significantly older and had significantly higher proportions of alcohol abuse, smoking, and arterial hypertension and higher levels of white blood cell and low-density lipoprotein. However, statistical analyses with and without PSM did not find any significant association between ischemic stroke and portal vein thrombosis in patients with liver cirrhosis. CONCLUSION Ischemic stroke might not be associated with portal vein thrombosis in liver cirrhosis.
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Affiliation(s)
- Kexin Zheng
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command (Formerly General Hospital of Shenyang Military Area), Shenyang, Liaoning Province, China
- Postgraduate College, Jinzhou Medical University, Jinzhou, Liaoning Province, China
| | - Xiaozhong Guo
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command (Formerly General Hospital of Shenyang Military Area), Shenyang, Liaoning Province, China
| | - Fangfang Yi
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command (Formerly General Hospital of Shenyang Military Area), Shenyang, Liaoning Province, China
- Postgraduate College, Dalian Medical University, Dalian, Liaoning Province, China
| | - Le Wang
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command (Formerly General Hospital of Shenyang Military Area), Shenyang, Liaoning Province, China
- Postgraduate College, Dalian Medical University, Dalian, Liaoning Province, China
| | - Andrea Mancuso
- Medicina Interna 1, Azienda di Rilievo Nazionale ad Alta Specializzazione Civico-Di Cristina-Benfratelli, Piazzale Leotta 4, 90100 Palermo, Italy
| | - Xingshun Qi
- Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command (Formerly General Hospital of Shenyang Military Area), Shenyang, Liaoning Province, China
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10
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Autoimmune Manifestations of Acute Q Fever Infection. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2018. [DOI: 10.1097/ipc.0000000000000629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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11
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Ponzetto A, Figura N, Cruz-Ramón V, Chinchilla-López P, Ramírez-Pérez O, Aguilar-Olivos NE, Alva-López LF, Fajardo-Ordoñez E, Ponciano-Rodríguez G, Northup PG, Intagliata N, Caldwell SH, Qi X, Méndez-Sánchez N. Thrombosis of the Portal Venous System in Cirrhotic Patients. Ann Hepatol 2018; 17:1078-1080. [PMID: 30600284 DOI: 10.5604/01.3001.0012.7209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Antonio Ponzetto
- Department of Medical Sciences, University of Torino Corso AM, Turin, Italy
| | - Natale Figura
- Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy
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Gravina AG, Zagari RM, De Musis C, Romano L, Loguercio C, Romano M. Helicobacter pylori and extragastric diseases: A review. World J Gastroenterol 2018; 24:3204-3221. [PMID: 30090002 PMCID: PMC6079286 DOI: 10.3748/wjg.v24.i29.3204] [Citation(s) in RCA: 196] [Impact Index Per Article: 28.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Revised: 05/19/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) infection is very common and affects approximately half of the world population. It causes gastric diseases, but some authors have reported an association of H. pylori infection with other systemic manifestations beginning in 1994. The list of potential effects of H. pylori outside the stomach includes a number of extragastric manifestations and we focused on neurological, dermatological, hematologic, ocular, cardiovascular, metabolic, allergic, and hepatobiliary diseases. This review discusses these important reported manifestations that are not related to the gastrointestinal tract.
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Affiliation(s)
- Antonietta Gerarda Gravina
- Dipartimento di “Medicina di Precisione”, UOC Epatogastroenterologia, Università della Campania “Luigi Vanvitelli”, Napoli 80131, Italy
| | - Rocco Maurizio Zagari
- Dipertimento Di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna 40138, Italy
| | - Cristiana De Musis
- Dipartimento di “Medicina di Precisione”, UOC Epatogastroenterologia, Università della Campania “Luigi Vanvitelli”, Napoli 80131, Italy
| | - Lorenzo Romano
- Dipartimento di “Medicina di Precisione”, UOC Epatogastroenterologia, Università della Campania “Luigi Vanvitelli”, Napoli 80131, Italy
| | - Carmelina Loguercio
- Dipartimento di “Medicina di Precisione”, UOC Epatogastroenterologia, Università della Campania “Luigi Vanvitelli”, Napoli 80131, Italy
| | - Marco Romano
- Dipartimento di “Medicina di Precisione”, UOC Epatogastroenterologia, Università della Campania “Luigi Vanvitelli”, Napoli 80131, Italy
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Sciascia S, Radin M, Bazzan M, Roccatello D. Antiphospholipid antibodies: crossroads between autoimmunity and infections? Intern Emerg Med 2017; 12:557-558. [PMID: 28405796 DOI: 10.1007/s11739-017-1664-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Accepted: 04/08/2017] [Indexed: 10/19/2022]
Affiliation(s)
- Savino Sciascia
- Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, S. Giovanni Bosco Hospital, University of Turin, Piazza del Donatore di Sangue 3, 10154, Turin, Italy.
- SCU Nephrology and Dialysis, S. Giovanni Bosco Hospital, Turin, Italy.
| | - Massimo Radin
- Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, S. Giovanni Bosco Hospital, University of Turin, Piazza del Donatore di Sangue 3, 10154, Turin, Italy
| | - Mario Bazzan
- UOSD Hematology and Thrombosis Unit, S. Giovanni Bosco Hospital, Turin, Italy
| | - Dario Roccatello
- Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases-Coordinating Center of Piemonte and Valle d'Aosta Network for Rare Diseases, S. Giovanni Bosco Hospital, University of Turin, Piazza del Donatore di Sangue 3, 10154, Turin, Italy
- SCU Nephrology and Dialysis, S. Giovanni Bosco Hospital, Turin, Italy
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Ponzetto A, Figura N, Caccioppo A. Anti-phospholipid syndrome therapy. Intern Emerg Med 2017; 12:555-556. [PMID: 28188576 DOI: 10.1007/s11739-017-1633-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Accepted: 02/06/2017] [Indexed: 10/20/2022]
Affiliation(s)
- Antonio Ponzetto
- Gastroenterology, Department of Medical Sciences, University of Torino, Corso AM Dogliotti 14, 10126, Turin, Italy.
| | - Natale Figura
- Gastroenterology, Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy
| | - Andrea Caccioppo
- Department of Medical Sciences, University of Torino, Turin, Italy
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Abstract
The etiology of autoimmune diseases is multifactorial. The degree to which genetic and environmental factors influence susceptibility to autoimmune diseases is poorly defined. It is believed that versatile clinical presentations of autoimmune diseases stem from various combinations of the genetic and environmental factors. One of the newly diagnosed autoimmune diseases is the antiphospholipid syndrome (APS). APS is characterized by vascular thrombosis, and/or pregnancy morbidity associated with anticardiolipin (aCL), anti-β2-glycoprotein-I (anti-β2GPI) and lupus anticoagulant (LAC).
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Affiliation(s)
- Y Levy
- Department of Medicine 'E', Meir Medical Center, Sheba Medical Center, Israel
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Lee HJ, Kang YM, Lee E, Jeong BJ, Jo YJ, Seong JS, Woo YM, Jeong KH. A Case of Azygos Vein Thombosis Associated with Transient Antiphospholipid Syndrome in Urinary Tract Infection withEscherichia coli. JOURNAL OF RHEUMATIC DISEASES 2016. [DOI: 10.4078/jrd.2016.23.2.118] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Affiliation(s)
- Hong Joo Lee
- Division of Nephrology, Department of Internal Medicine, Seoul Red Cross Hospital, Seoul, Korea
| | - Young Mo Kang
- Division of Nephrology, Department of Internal Medicine, Seoul Red Cross Hospital, Seoul, Korea
| | - Eun Lee
- Division of Nephrology, Department of Internal Medicine, Seoul Red Cross Hospital, Seoul, Korea
| | - Byum Jin Jeong
- Division of Nephrology, Department of Internal Medicine, Seoul Red Cross Hospital, Seoul, Korea
| | - Young Jun Jo
- Division of Nephrology, Department of Internal Medicine, Seoul Red Cross Hospital, Seoul, Korea
| | - Ji Seok Seong
- Division of Nephrology, Department of Internal Medicine, Seoul Red Cross Hospital, Seoul, Korea
| | - Yong Moon Woo
- Division of Nephrology, Department of Internal Medicine, Seoul Red Cross Hospital, Seoul, Korea
| | - Kyung Hwan Jeong
- Department of Nephrology, Kyung Hee University School of Medicine, Seoul, Korea
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Sarıcı SU, Gursel O, Kurekci E, Kesik V, Atay A, Okutan V, Inal A, Pekel A, Ozguven MA, Ozcan O. Anticardiolipin Antibodies in Children with Helicobacter pylori Infection. Helicobacter 2015; 20:418-21. [PMID: 25856798 DOI: 10.1111/hel.12226] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Abstract
BACKGROUND Anticardiolipin (aCL) antibodies are associated with thrombosis and have an important role in the etiology of diseases such as stroke and myocardial infarction whose etiologies were based on thrombosis. H. pylori has been proposed to be responsible for the pathophysiology of some diseases including stroke, myocardial infarction, thrombosis, and autoimmune diseases. From this point of view, we hypothesized a possible relationship between H. pylori infection and aCL antibodies and initially aimed to determine the prevalence of aCL antibody positivity in children with H. pylori infection. MATERIALS AND METHODS Anticardiolipin antibodies were studied in 84 patients before and after eradication therapy and in a control group including 40 children. RESULTS The pretreatment aCL IgA (median 12.78 APL/mL), aCL IgM (median 21.60 MPL/mL), and aCL IgG antibody levels (median 14.22 GPL/mL) were significantly higher than those of post-treatment results (median 5.38 APL/mL, 7.02 MPL/mL, and 6.64 GPL/mL, respectively) and controls (median 5.90 APL/mL, 4.80 MPL/mL, and 4.81 GPL/mL, respectively). Anticardiolipin antibodies revealed no significant differences between the study group after therapy and the control group. CONCLUSIONS In our particular experience, H. pylori can cause aCL antibody positivity in children and eradication of H. pylori provides the disappearance of these antibodies.
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Affiliation(s)
- Serdar Umit Sarıcı
- Department of Pediatrics, Gulhane Military Medical Academy and Medical Faculty, Ankara, Turkey
| | - Orhan Gursel
- Department of Pediatrics, Gulhane Military Medical Academy and Medical Faculty, Ankara, Turkey
| | - Emin Kurekci
- Department of Pediatrics, Gulhane Military Medical Academy and Medical Faculty, Ankara, Turkey
| | - Vural Kesik
- Department of Pediatrics, Gulhane Military Medical Academy and Medical Faculty, Ankara, Turkey
| | - Avni Atay
- Department of Pediatrics, Gulhane Military Medical Academy and Medical Faculty, Ankara, Turkey
| | - Vedat Okutan
- Department of Pediatrics, Gulhane Military Medical Academy and Medical Faculty, Ankara, Turkey
| | - Ali Inal
- Department of Immunology, Gulhane Military Medical Academy and Medical Faculty, Ankara, Turkey
| | - Aysel Pekel
- Department of Immunology, Gulhane Military Medical Academy and Medical Faculty, Ankara, Turkey
| | - Mehmet Ali Ozguven
- Department of Nuclear Medicine, Gulhane Military Medical Academy and Medical Faculty, Ankara, Turkey
| | - Okan Ozcan
- Department of Pediatrics, Gulhane Military Medical Academy and Medical Faculty, Ankara, Turkey
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Blank M, Israeli E, Cervera R. The Infectious Origin of the Anti-Phospholipid Syndrome. INFECTION AND AUTOIMMUNITY 2015:681-696. [DOI: 10.1016/b978-0-444-63269-2.00045-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Campuzano-Maya G. Hematologic manifestations of Helicobacter pylori infection. World J Gastroenterol 2014; 20:12818-12838. [PMID: 25278680 PMCID: PMC4177465 DOI: 10.3748/wjg.v20.i36.12818] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2014] [Revised: 06/10/2014] [Accepted: 07/16/2014] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is the most common infection in humans, with a marked disparity between developed and developing countries. Although H. pylori infections are asymptomatic in most infected individuals, they are intimately related to malignant gastric conditions such as gastric cancer and gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to benign diseases such as gastritis and duodenal and gastric peptic ulcers. Since it was learned that bacteria could colonize the gastric mucosa, there have been reports in the medical literature of over 50 extragastric manifestations involving a variety medical areas of specialization. These areas include cardiology, dermatology, endocrinology, gynecology and obstetrics, hematology, pneumology, odontology, ophthalmology, otorhinolaryngology and pediatrics, and they encompass conditions with a range of clear evidence between the H. pylori infection and development of the disease. This literature review covers extragastric manifestations of H. pylori infection in the hematology field. It focuses on conditions that are included in international consensus and management guides for H. pylori infection, specifically iron deficiency, vitamin B12 (cobalamin) deficiency, immune thrombocytopenia, and MALT lymphoma. In addition, there is discussion of other conditions that are not included in international consensus and management guides on H. pylori, including auto-immune neutropenia, antiphospholipid syndrome, plasma cell dyscrasias, and other hematologic diseases.
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Abstract
The discovery of Helicobacter pylori infection in the stomach could be considered as one of the most important events of modern gastroenterology. Understanding of the natural history of many disorders of the upper gastrointestinal tract, including chronic gastritis, peptic ulcer disease, gastric cancer and MALT lymphoma, was altered by this discovery. Interestingly, epidemiological studies have also revealed a correlation between H. pylori infection and some diseases localized outside the stomach, especially those characterized by persistent and low-grade systemic inflammation. Of note, H. pylori has an important role in iron deficiency anaemia, idiopathic thrombocytopenic purpura and vitamin B12 deficiency. Moreover, the association of this bacterial pathogen with many other diseases, including hepatobiliary, pancreatic, cardiovascular and neurodegenerative disorders is currently under investigation. In this Review, we summarize the results of the most important studies performed to date surrounding the association of H. pylori infection with extragastric diseases, as well as the strength of the evidence. We also provide information concerning bacterial-host interactions and the mechanisms implicated in the pathogenesis of each of these extragastric diseases.
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Rosman Y, Lidar M, Shoenfeld Y. Antibiotic therapy in autoimmune disorders. ACTA ACUST UNITED AC 2014. [DOI: 10.2217/cpr.13.84] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Matsukawa Y, Hara H, Aoki M, Inada K, Kaneko M, Mitamura K, Sawada U, Sawada S, Horie T, Ochiai T. Toxic epidermal necrolysis induced by a triple-drug regimen for helicobacter pylori eradication. Clin Drug Investig 2012; 24:301-3. [PMID: 17503892 DOI: 10.2165/00044011-200424050-00007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Affiliation(s)
- Yoshihiro Matsukawa
- Department of Internal Medicine I, Nihon University School of Medicine, Tokyo, Japan
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Polyzos SA, Kountouras J, Zavos C, Deretzi G. The association between Helicobacter pylori infection and insulin resistance: a systematic review. Helicobacter 2011; 16:79-88. [PMID: 21435084 DOI: 10.1111/j.1523-5378.2011.00822.x] [Citation(s) in RCA: 151] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Helicobacter pylori infection has been associated with diverse extradigestive morbidity, including insulin resistance (IR) syndrome. The aim of this systematic review was to summarize the epidemiologic evidence concerning the association between H. pylori infection and IR quantitative indexes. MATERIALS AND METHODS A computerized literature search in PubMed electronic databases and Cochrane Central Register of Controlled Trials was performed. RESULTS Nine studies reporting data on 2120 participants were finally eligible for this systematic review. Seven of them were cross-sectional studies and two were nonrandomized, open-label, controlled trials investigating the effect of H. pylori eradication on IR. Homeostatic model of assessment insulin resistance (HOMA-IR) was used in all studies to quantify IR. There seems to be a trend toward a positive association between H. pylori infection and HOMA-IR, strengthened by regression analysis in one study. However, there was significant heterogeneity between studies regarding the method(s) of H. pylori infection diagnosis based on and the study populations. The studies for the effect of H. pylori eradication on HOMA-IR revealed conflicting results. CONCLUSIONS Although data seem to indicate a potential association between H. pylori infection and IR, further studies are needed to strengthen this association and to clarify whether there is a causative link between them. If a causal link is confirmed in the future, this may have a major impact on the pathophysiology and management of IR syndrome, including type 2 diabetes mellitus and nonalcoholic fatty liver disease.
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Affiliation(s)
- Stergios A Polyzos
- Second Medical Clinic, Medical School, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Macedonia, Greece
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Chen YW, Nagasawa T, Wara-Aswapati N, Ushida Y, Wang D, Takeuchi Y, Kobayashi H, Umeda M, Inoue Y, Iwai T, Ishikawa I, Izumi Y. Association between periodontitis and anti-cardiolipin antibodies in Buerger disease. J Clin Periodontol 2009; 36:830-5. [PMID: 19678860 DOI: 10.1111/j.1600-051x.2009.01467.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
AIM Anti-cardiolipin (CL) antibodies can be induced in Buerger disease (BD), an inflammatory occlusive disorder affecting peripheral blood vessels, in response to bacteria bearing homology to the TLRVYK peptide of a phospholipid-binding plasma protein beta-2-glycoprotein I. TLRVYK homologies are present in Porphyromonas gingivalis (TLRIYT) and Treponema denticola (TLALYK). This study investigated the association between periodontal infection and anti-CL antibodies in BD patients. MATERIAL AND METHODS Periodontal conditions were examined in 19 BD patients and 25 systemically healthy control subjects. All subjects were heavy smokers. Serum anti-CL, anti-TLRVYK, anti-TLRIYT, and anti-TLALYK antibodies were assessed using the enzyme-linked immunosorbent assay. RESULTS BD patients had a significantly higher prevalence of periodontitis, more severe periodontal destruction and increased titres of serum anti-CL, anti-TLRVYK, anti-TLRIYT, and anti-TLALYK antibodies compared with healthy subjects. The levels of anti-CL antibodies positively correlated with those of the three anti-peptide antibodies. Anti-CL antibody titres were significantly associated with the percentage of sites with clinical attachment level >or=4 mm in BD patients. CONCLUSION Elevated anti-CL antibody levels were associated with periodontal destruction in BD patients. Periodontopathic bacteria may serve as exogenous antigens that stimulate the anti-CL antibody production through molecular mimicry between the bacterial peptides and a host plasma protein.
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Affiliation(s)
- Yi-Wen Chen
- Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
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Affiliation(s)
- Junta Imai
- Department of Diabetes and Metabolism, Tohoku University Hospital, Sendai, Miyagi 980-8575, Japan
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Wang D, Nagasawa T, Chen Y, Ushida Y, Kobayashi H, Takeuchi Y, Umeda M, Izumi Y. Molecular mimicry of Aggregatibacter actinomycetemcomitans with beta2 glycoprotein I. ACTA ACUST UNITED AC 2008; 23:401-5. [PMID: 18793363 DOI: 10.1111/j.1399-302x.2008.00442.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
INTRODUCTION beta2-Glycoprotein I (beta 2GPI) is important in the suppression of coagulation, and antibodies against TLRVYK peptides on the beta 2GPI molecule are related to thrombosis. According to the Swiss-Prot database, Aggregatibacter actinomycetemcomitans leukotoxin c has sequences (SIRVYK) that are homologous to the TLRVYK peptides. The aim of this study was to investigate the effects of A. actinomycetemcomitans infection on the antibody response against SIRVYK peptides in patients with periodontitis. METHODS Serum immunoglobulin G (IgG) antibody and IgG subclass antibody titers against SIRVYK or TLRVYK peptides were measured by enzyme-linked immunosorbent assay in 46 patients with aggressive periodontitis (eight with localized disease, 38 with generalized disease), 28 patients with chronic periodontitis, and 20 periodontally healthy subjects. The presence of A. actinomycetemcomitans in plaque and saliva samples was determined using polymerase chain reaction. RESULTS The level of anti-SIRVYK antibodies was significantly higher in patients who were A. actinomycetemcomitans-positive than in A. actinomycetemcomitans-negative patients (P < 0.05) in the chronic periodontitis group. A similar trend was found in the antibody response to TLRVYK peptide; however, no statistically significant difference was seen between A. actinomycetemcomitans-positive and -negative patients. The A. actinomycetemcomitans-positive patients displayed significantly higher levels of anti-SIRVYK IgG2 and IgG3 antibodies than A. actinomycetemcomitans-negative patients (P < 0.05 and P < 0.05, respectively). The level of IgG2 was highest among the four IgG subclasses and it predominantly increased in patients who were A. actinomycetemcomitans-positive. Anti-TLRVYK antibody levels were significantly correlated with anti-SIRVYK IgG antibody levels. CONCLUSION The results suggest that A. actinomycetemcomitans infection may elicit anti-SIRVYK IgG antibodies and modify the anti-TLRVYK antibody response in patients with periodontitis by molecular mimicry with beta2GPI.
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Affiliation(s)
- D Wang
- Department of Hard Tissue Engineering, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
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Shoenfeld Y, Blank M, Cervera R, Font J, Raschi E, Meroni PL. Infectious origin of the antiphospholipid syndrome. Ann Rheum Dis 2006; 65:2-6. [PMID: 16344491 PMCID: PMC1797971 DOI: 10.1136/ard.2005.045443] [Citation(s) in RCA: 135] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
From a systemic disease towards the infectious aetiology
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Harel M, Aron-Maor A, Sherer Y, Blank M, Shoenfeld Y. The infectious etiology of the antiphospholipid syndrome: links between infection and autoimmunity. Immunobiology 2005; 210:743-7. [PMID: 16325492 DOI: 10.1016/j.imbio.2005.10.004] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2005] [Accepted: 08/30/2005] [Indexed: 11/19/2022]
Abstract
Like many other autoimmune diseases, the antiphospholipid syndrome (APS) is considered as of a multifactorial etiology, mainly genetic susceptibility coinciding with environmental triggers, of which infectious agents are considered most prominent. Different clinical and experimental studies of the beta2 glycoprotein I (beta 2 GPI) molecule, one of the target autoantigens in APS, have linked infection to the development of APS. Using a peptide phage library, it has been shown that target epitopes of beta 2 GPI share similarities with common infectious pathogens. Also, circulating anti-beta 2 GPI antibodies have been identified in the sera of patients with different infectious conditions, and have been associated with various clinical APS manifestations. Molecular mimicry as a key mechanism linking infection and APS has been demonstrated in experimental models. In these studies, APS was induced by immunization of mice to various microbial pathogens. Anti-beta 2 GPI titers were found to be especially high following immunization with Haemophilus influenzae, Neisseria gonorrheae or tetanus toxoid. These findings contribute greatly to the understanding of APS pathogenesis, as well as create new directions for therapy modalities, namely specific peptide toleragens and antimicrobial treatment.
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Affiliation(s)
- Michal Harel
- Department of Medicine 'B' and Center of Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 52621, Israel
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Blank M, Shoenfeld Y. Beta-2-glycoprotein-I, infections, antiphospholipid syndrome and therapeutic considerations. Clin Immunol 2004; 112:190-9. [PMID: 15240163 DOI: 10.1016/j.clim.2004.02.018] [Citation(s) in RCA: 58] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2004] [Accepted: 02/27/2004] [Indexed: 11/28/2022]
Abstract
Evidence supports the association between infectious agents, antiphospholipid syndrome (APS), and the presence of antiphospholipid antibodies and anti-beta2-glycoprotein-I (beta2GPI) antibodies. Several mechanisms have been proposed to explain the role of bacteria/viruses in induction of an autoimmune condition, such as molecular mimicry between structures of a pathogen and self antigen and bystander activation or bacterial/viral superantigens. Protein databases reveal high homologies between the beta2GPI-related synthetic peptides and infectious agents. Studies employing experimental APS models proved molecular mimicry between beta2GPI-related synthetic peptides, which serve as target epitopes for anti-beta2GPI Abs, and structures within bacteria, viruses (e.g., CMV), and tetanus toxoid. Any explanation of how microbial infections might induce APS must take into account the genetic predisposition. In this paper, we discuss the association of antiphospholipid antibodies, infectious states, and molecular mimicry as a proposed mechanism for development of APS.
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Affiliation(s)
- Miri Blank
- Department of Medicine B and The Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 52621, Israel
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Preusch MR, Grau AJ, Buggle F, Lichy C, Bartel J, Black C, Rudi J. Association Between Cerebral Ischemia and Cytotoxin-Associated Gene-A–Bearing Strains ofHelicobacter pylori. Stroke 2004; 35:1800-4. [PMID: 15166387 DOI: 10.1161/01.str.0000131751.35926.48] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
BACKGROUND AND PURPOSE Studies on Helicobacter pylori infection and risk of ischemic stroke yielded variable results. Infection with more virulent H. pylori strains, such as cytotoxin-associated gene-A (CagA)-bearing strains, may be of particular relevance for ischemic diseases. We investigated whether H. pylori and CagA seropositivity are independent risk factors for cerebral ischemia or its etiologic subtypes. METHODS We determined IgG antibodies against H. pylori and CagA protein (enzyme immunoassays) in 190 patients with acute cerebral ischemia and in 229 age- and sex-matched control subjects selected randomly from the general population. RESULTS CagA seropositivity was more common in patients (114/190; 60.0%) than in control subjects (99/229; 43.2%; odds ratio, 1.97; 95% CI, 1.33 to 2.91; P<0.001). This result remained significant after adjustment for age, sex, vascular risk factors and diseases, and childhood and adult social status (odds ratio, 1.84; 95% CI, 1.13 to 3.00; P=0.015). Subgroup analyses yielded similar results in all etiologic stroke subtypes. In contrast, H. pylori seropositivity in general was not associated with increased risk of stroke or its etiologic subtypes. CONCLUSIONS Our results support the hypothesis of an association between infection with CagA-positive H. pylori strains and acute cerebral ischemia.
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Blank M, Eisenstein M, Asherson R, Cervera R, Shoenfeld Y. The Infectious Origin of the Antiphospholipid Syndrome. INFECTION AND AUTOIMMUNITY 2004:473-490. [DOI: 10.1016/b978-044451271-0.50037-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Fischer K, Collins H, Taniguchi M, Kaufmann SHE, Schaible UE. IL-4 and T cells are required for the generation of IgG1 isotype antibodies against cardiolipin. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2002; 168:2689-94. [PMID: 11884434 DOI: 10.4049/jimmunol.168.6.2689] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Infection with Mycobacterium tuberculosis induces Abs against a vast array of mycobacterial lipids and glycolipids. One of the most prominent lipid Ags recognized is cardiolipin (CL). The kinetics of the generation of anti-CL Abs during infection reveals that IgM titers to CL increase over time. Interestingly, at day 30 postinfection CL-specific IgG1 appears, an isotype usually dependent on T cell help. Using an immunization schedule with CL/anti-CL Ab complexes, which induces antiphospholipid syndrome in mice, we show that the generation of IgG1 to CL requires IL-4 and that optimal production is T cell dependent. IgG1 production to CL was impaired in nude (nu/nu) mice devoid in conventional T cells, but was not affected in mice deficient for either alphabeta TCR(+), gammadelta TCR(+), CD4(+), CD8(+), or NK1.1(+) T cells. We conclude that IgG1 production to CL depends on T cell help and IL-4, which can be provided by different T cell populations. This is the first report that IL-4 is indispensable for the induction of IgG1 Abs to lipid Ags.
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Affiliation(s)
- Karsten Fischer
- Department of Immunology, Max-Planck-Institute for Infection Biology, Berlin, Germany
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