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      Immune responses against Helicobacter pylori-specific antigens differentiate relapsing remitting from secondary progressive multiple sclerosis

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          Abstract

          To assess whether Helicobacter pylori (Hp) antibody (ab) reactivity against individual Hp antigens is pathogenetically relevant to multiple sclerosis (MS), we systematically investigated prevalence and clinical significance of abs against 14 immunodominant and subdominant Hp antigens by ELISA and immunoblotting in 139 consecutive MS patients with relapsing-remitting (RRMS, n = 102) or secondary progressive (SPMS, n = 37). Sera from 39 patients with Parkinson’s disease (PD), 21 with Alzheimer’s disease (ALZ) and 68 healthy controls (HCs), were also tested. Anti-flagellin (18.3%) and anti-p41 (25.0%) abs in MS were less frequent than in HCs (39.4%, 48.5%, respectively). Abs against 5 of the 14 antigens were less frequent in RRMS than HCs, including p41, p54-flagellin, p29-UreA, p67-FSH, and p120-CagA. Anti-VacA abs were more frequent in SPMS than in HCs (42.1 vs 12.1%, p = 0.019). Anti-p54, anti-p29-UreA and anti-p26 correlated with extended disability status scale (EDSS) ( p = 0.017, p = 0.005, p = 0.002, respectively). Anti-p26 and anti-p17 correlated with the number of relapses ( p = 0.037 and p = 0.047, respectively). This is the first comprehensive analysis of ab reactivities against most Hp antigens in MS patients. Ab responses differ between MS and HCs and between RRMS and SPMS, being more prevalent in SPMS than RRMS, thus suggesting an association between anti-Hp and the former type of MS.

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          The role of heat shock proteins in atherosclerosis.

          Atherosclerosis is a chronic, multifactorial disease that starts in youth, manifests clinically later in life, and can lead to myocardial infarction, stroke, claudication, and death. Although inflammatory processes have long been known to be involved in atherogenesis, interest in this subject has grown in the past 30-40 years. Animal experiments and human analyses of early atherosclerotic lesions have shown that the first pathogenic event in atherogenesis is the intimal infiltration of T cells at arterial branching points. These T cells recognize heat shock protein (HSP)60, which is expressed together with adhesion molecules by endothelial cells in response to classic risk factors for atherosclerosis. Although these HSP60-reactive T cells initiate atherosclerosis, antibodies to HSP60 accelerate and perpetuate the disease. All healthy humans develop cellular and humoral immunity against microbial HSP60 by infection or vaccination. Given that prokaryotic (bacterial) and eukaryotic (for instance, human) HSP60 display substantial sequence homology, atherosclerosis might be the price we pay for this protective immunity, if risk factors stress the vascular endothelial cells beyond physiological conditions.
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            Helicobacter pylori and autoimmune disease: cause or bystander.

            Helicobacter pylori (H. pylori) is the main cause of chronic gastritis and a major risk factor for gastric cancer. This pathogen has also been considered a potential trigger of gastric autoimmunity, and in particular of autoimmune gastritis. However, a considerable number of reports have attempted to link H. pylori infection with the development of extra-gastrointestinal autoimmune disorders, affecting organs not immediately relevant to the stomach. This review discusses the current evidence in support or against the role of H. pylori as a potential trigger of autoimmune rheumatic and skin diseases, as well as organ specific autoimmune diseases. We discuss epidemiological, serological, immunological and experimental evidence associating this pathogen with autoimmune diseases. Although over one hundred autoimmune diseases have been investigated in relation to H. pylori, we discuss a select number of papers with a larger literature base, and include Sjögrens syndrome, rheumatoid arthritis, systemic lupus erythematosus, vasculitides, autoimmune skin conditions, idiopathic thrombocytopenic purpura, autoimmune thyroid disease, multiple sclerosis, neuromyelitis optica and autoimmune liver diseases. Specific mention is given to those studies reporting an association of anti-H. pylori antibodies with the presence of autoimmune disease-specific clinical parameters, as well as those failing to find such associations. We also provide helpful hints for future research.
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              Helicobacter pylori infection is a potential protective factor against conventional multiple sclerosis in the Japanese population.

              Persistent Helicobacter pylori (H. pylori) infection is a chronic inflammatory stimulus to hosts with an inverse correlation to atopic disorders. In this study, a total of 105 consecutive multiple sclerosis (MS) patients were divided into 52 opticospinal MS (OSMS) and 53 conventional MS (CMS), and their sera, along with those from 85 healthy controls (HC), were examined by an enzyme-linked immunosorbent assay using antibodies against H. pylori. H. pylori seropositivity was significantly lower in patients with CMS (22.6%) compared with HC (42.4%) and patients with OSMS (51.9%) (p=0.0180 and p=0.0019, respectively). In patients with CMS, H. pylori seropositivity showed a significant inverse association with mean EDSS score and fulfillment of McDonald MRI criteria for space (OR=0.61, p=0.0344 and OR=0.11, p=0.0297). These findings suggest that H. pylori infection is a protective factor against CMS in Japanese.
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                Author and article information

                Contributors
                bogdanos@med.uth.gr
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                11 August 2017
                11 August 2017
                2017
                : 7
                : 7929
                Affiliations
                [1 ]ISNI 0000 0001 0035 6670, GRID grid.410558.d, Department of Rheumatology and Clinical Immunology, , University General Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Viopolis, ; 40500 Larissa, Greece
                [2 ]ISNI 0000 0001 0035 6670, GRID grid.410558.d, Department of Neurology, , University General Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, ; 40500 Larissa, Greece
                [3 ]Cellular Immunotherapy & Molecular Immunodiagnostics, Biomedical Section, Centre for Research and Technology-Hellas (CERTH) - Institute for Research and Technology-Thessaly (IRETETH), 41222 Larissa, Greece
                [4 ]ISNI 0000 0001 0035 6670, GRID grid.410558.d, Department of Internal Medicine, , University General Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, ; 40500 Larissa, Greece
                [5 ]Institute of Experimental Immunology, affiliated to EUROIMMUN AG, Lubeck, Germany
                [6 ]ISNI 0000 0001 0035 6670, GRID grid.410558.d, Department of Obstetrics and Gynecology, , University General Hospital of Larissa, Faculty of Medicine, School of Health Sciences, University of Thessaly, Viopolis, ; 40500 Larissa, Greece
                Author information
                http://orcid.org/0000-0003-2957-641X
                Article
                7801
                10.1038/s41598-017-07801-9
                5554191
                28801580
                90d0d154-8a9e-4334-8106-e07013e523e8
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 12 April 2017
                : 29 June 2017
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