{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T23:14:14Z","timestamp":1769814854379,"version":"3.49.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T00:00:00Z","timestamp":1502409600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T00:00:00Z","timestamp":1502409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To assess whether <jats:italic>Helicobacter pylori<\/jats:italic> (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\u2009=\u2009102) or secondary progressive (SPMS, n\u2009=\u200937). Sera from 39 patients with Parkinson\u2019s disease (PD), 21 with Alzheimer\u2019s 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 <jats:italic>vs<\/jats:italic> 12.1%, <jats:italic>p<\/jats:italic>\u2009=\u20090.019). Anti-p54, anti-p29-UreA and anti-p26 correlated with extended disability status scale (EDSS) (<jats:italic>p\u2009=\u2009<\/jats:italic>0.017, <jats:italic>p\u2009=\u2009<\/jats:italic>0.005, <jats:italic>p\u2009=\u2009<\/jats:italic>0.002, respectively). Anti-p26 and anti-p17 correlated with the number of relapses (<jats:italic>p\u2009=\u2009<\/jats:italic>0.037 and <jats:italic>p\u2009=\u2009<\/jats:italic>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.<\/jats:p>","DOI":"10.1038\/s41598-017-07801-9","type":"journal-article","created":{"date-parts":[[2017,8,7]],"date-time":"2017-08-07T13:37:13Z","timestamp":1502113033000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Immune responses against Helicobacter pylori-specific antigens differentiate relapsing remitting from secondary progressive multiple sclerosis"],"prefix":"10.1038","volume":"7","author":[{"given":"Georgios","family":"Efthymiou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2957-641X","authenticated-orcid":false,"given":"Efthymios","family":"Dardiotis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christos","family":"Liaskos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanouela","family":"Marou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vana","family":"Tsimourtou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eirini I.","family":"Rigopoulou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Scheper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandros","family":"Daponte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lazaros I.","family":"Sakkas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgios","family":"Hadjigeorgiou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitrios P.","family":"Bogdanos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,8,11]]},"reference":[{"key":"7801_CR1","first-page":"353","volume":"28","author":"E Gavalas","year":"2015","unstructured":"Gavalas, E. et al. Relationship between Helicobacter pylori infection and multiple sclerosis. Annals of gastroenterology \n                           28, 353\u2013356 (2015).","journal-title":"Annals of gastroenterology"},{"key":"7801_CR2","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1177\/1352458509360550","volume":"16","author":"J Kountouras","year":"2010","unstructured":"Kountouras, J. et al. Helicobacter pylori with or without its neutrophil-activating protein may be the common denominator associated with multiple sclerosis and neuromyelitis optica. Multiple sclerosis \n                           16, 376\u2013377, doi:10.1177\/1352458509360550 (2010). author reply 378\u2013379doi:.","journal-title":"Multiple sclerosis"},{"key":"7801_CR3","doi-asserted-by":"publisher","first-page":"e73","DOI":"10.1515\/cclm-2012-0753","volume":"51","author":"J Kountouras","year":"2013","unstructured":"Kountouras, J. et al. Relationship between Helicobacter pylori infection and autoimmune disorders. Clinical chemistry and laboratory medicine \n                           51, e73\u201374, doi:10.1515\/cclm-2012-0753 (2013).","journal-title":"Clinical chemistry and laboratory medicine"},{"key":"7801_CR4","doi-asserted-by":"publisher","first-page":"613","DOI":"10.3748\/wjg.v20.i3.613","volume":"20","author":"DS Smyk","year":"2014","unstructured":"Smyk, D. S. et al. Helicobacter pylori and autoimmune disease: cause or bystander. World journal of gastroenterology \n                           20, 613\u2013629, doi:10.3748\/wjg.v20.i3.613 (2014).","journal-title":"World journal of gastroenterology"},{"key":"7801_CR5","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3389\/fmicb.2015.00052","volume":"6","author":"KW Cook","year":"2015","unstructured":"Cook, K. W. et al. Helicobacter pylori infection reduces disease severity in an experimental model of multiple sclerosis. Frontiers in microbiology \n                           6, 52, doi:10.3389\/fmicb.2015.00052 (2015).","journal-title":"Frontiers in microbiology"},{"key":"7801_CR6","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.jneuroim.2006.12.010","volume":"184","author":"W Li","year":"2007","unstructured":"Li, W. et al. Helicobacter pylori infection is a potential protective factor against conventional multiple sclerosis in the Japanese population. Journal of neuroimmunology \n                           184, 227\u2013231, doi:10.1016\/j.jneuroim.2006.12.010 (2007).","journal-title":"Journal of neuroimmunology"},{"key":"7801_CR7","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1159\/000345838","volume":"20","author":"Y Long","year":"2013","unstructured":"Long, Y. et al. Helicobacter pylori infection in Neuromyelitis Optica and Multiple Sclerosis. Neuroimmunomodulation \n                           20, 107\u2013112, doi:10.1159\/000345838 (2013).","journal-title":"Neuroimmunomodulation"},{"key":"7801_CR8","doi-asserted-by":"publisher","first-page":"e0124064","DOI":"10.1371\/journal.pone.0124064","volume":"10","author":"C Malli","year":"2015","unstructured":"Malli, C., Pandit, L., D\u2019Cunha, A. & Mustafa, S. Environmental factors related to multiple sclerosis in Indian population. PloS one \n                           10, e0124064, doi:10.1371\/journal.pone.0124064 (2015).","journal-title":"PloS one"},{"key":"7801_CR9","doi-asserted-by":"publisher","first-page":"31","DOI":"10.4081\/ni.2013.e10","volume":"5","author":"N Mohebi","year":"2013","unstructured":"Mohebi, N., Mamarabadi, M. & Moghaddasi, M. Relation of helicobacter pylori infection and multiple sclerosis in Iranian patients. Neurology international \n                           5, 31\u201333, doi:10.4081\/ni.2013.e10 (2013).","journal-title":"Neurology international"},{"key":"7801_CR10","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1136\/jnnp-2014-309495","volume":"86","author":"MJ Pedrini","year":"2015","unstructured":"Pedrini, M. J. et al. Helicobacter pylori infection as a protective factor against multiple sclerosis risk in females. Journal of neurology, neurosurgery, and psychiatry \n                           86, 603\u2013607, doi:10.1136\/jnnp-2014-309495 (2015).","journal-title":"Journal of neurology, neurosurgery, and psychiatry"},{"key":"7801_CR11","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1177\/1352458509348961","volume":"15","author":"W Li","year":"2009","unstructured":"Li, W. et al. Association of anti-Helicobacter pylori neutrophil-activating protein antibody response with anti-aquaporin-4 autoimmunity in Japanese patients with multiple sclerosis and neuromyelitis optica. Multiple sclerosis \n                           15, 1411\u20131421, doi:10.1177\/1352458509348961 (2009).","journal-title":"Multiple sclerosis"},{"key":"7801_CR12","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.jaut.2004.03.002","volume":"22","author":"DP Bogdanos","year":"2004","unstructured":"Bogdanos, D. P. et al. Disease-specific cross-reactivity between mimicking peptides of heat shock protein of Mycobacterium gordonae and dominant epitope of E2 subunit of pyruvate dehydrogenase is common in Spanish but not British patients with primary biliary cirrhosis. Journal of autoimmunity \n                           22, 353\u2013362, doi:10.1016\/j.jaut.2004.03.002 (2004).","journal-title":"Journal of autoimmunity"},{"key":"7801_CR13","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.jri.2012.01.003","volume":"93","author":"A Daponte","year":"2012","unstructured":"Daponte, A., Pournaras, S., Deligeoroglou, E., Skentou, H. & Messinis, I. E. Serum interleukin-1beta, interleukin-8 and anti-heat shock 60 Chlamydia trachomatis antibodies as markers of ectopic pregnancy. Journal of reproductive immunology \n                           93, 102\u2013108, doi:10.1016\/j.jri.2012.01.003 (2012).","journal-title":"Journal of reproductive immunology"},{"key":"7801_CR14","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.jneuroim.2016.06.009","volume":"298","author":"G Efthymiou","year":"2016","unstructured":"Efthymiou, G. et al. Anti-hsp60 antibody responses based on Helicobacter pylori in patients with multiple sclerosis: (ir)Relevance to disease pathogenesis. Journal of neuroimmunology \n                           298, 19\u201323, doi:10.1016\/j.jneuroim.2016.06.009 (2016).","journal-title":"Journal of neuroimmunology"},{"key":"7801_CR15","doi-asserted-by":"publisher","first-page":"22486","DOI":"10.1038\/srep22486","volume":"6","author":"H Shoda","year":"2016","unstructured":"Shoda, H. et al. Immune responses to Mycobacterial heat shock protein 70 accompany self-reactivity to human BiP in rheumatoid arthritis. Scientific reports \n                           6, 22486, doi:10.1038\/srep22486 (2016).","journal-title":"Scientific reports"},{"key":"7801_CR16","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1038\/nrcardio.2014.91","volume":"11","author":"G Wick","year":"2014","unstructured":"Wick, G., Jakic, B., Buszko, M., Wick, M. C. & Grundtman, C. The role of heat shock proteins in atherosclerosis. Nature reviews. Cardiology \n                           11, 516\u2013529, doi:10.1038\/nrcardio.2014.91 (2014).","journal-title":"Nature reviews. Cardiology"},{"key":"7801_CR17","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/1757-4749-6-10","volume":"6","author":"A Michel","year":"2014","unstructured":"Michel, A., Pawlita, M., Boeing, H., Gissmann, L. & Waterboer, T. Helicobacter pylori antibody patterns in Germany: a cross-sectional population study. Gut pathogens \n                           6, 10, doi:10.1186\/1757-4749-6-10 (2014).","journal-title":"Gut pathogens"},{"key":"7801_CR18","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1097\/MEG.0b013e3282f5e9db","volume":"20","author":"MJ Goo","year":"2008","unstructured":"Goo, M. J. et al. Primary biliary cirrhosis, similar to that in human beings, in a male C57BL\/6 mouse infected with Helicobacter pylori. European journal of gastroenterology & hepatology \n                           20, 1045\u20131048, doi:10.1097\/MEG.0b013e3282f5e9db (2008).","journal-title":"European journal of gastroenterology & hepatology"},{"key":"7801_CR19","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1097\/MEG.0b013e32831a4807","volume":"21","author":"A Koutsoumpas","year":"2009","unstructured":"Koutsoumpas, A., Mytilinaiou, M., Polymeros, D., Dalekos, G. N. & Bogdanos, D. P. Anti-Helicobacter pylori antibody responses specific for VacA do not trigger primary biliary cirrhosis-specific antimitochondrial antibodies. European journal of gastroenterology & hepatology \n                           21, 1220, doi:10.1097\/MEG.0b013e32831a4807 (2009).","journal-title":"European journal of gastroenterology & hepatology"},{"key":"7801_CR20","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1136\/jnnp.73.1.76","volume":"73","author":"S Chiba","year":"2002","unstructured":"Chiba, S. et al. An antibody to VacA of Helicobacter pylori in cerebrospinal fluid from patients with Guillain-Barre syndrome. Journal of neurology, neurosurgery, and psychiatry \n                           73, 76\u201378 (2002).","journal-title":"Journal of neurology, neurosurgery, and psychiatry"},{"key":"7801_CR21","doi-asserted-by":"publisher","first-page":"2184","DOI":"10.1212\/01.WNL.0000145705.82690.04","volume":"63","author":"S Chiba","year":"2004","unstructured":"Chiba, S. et al. An antibody to VacA of Helicobacter pylori in the CSF of patients with Miller-Fisher syndrome. Neurology \n                           63, 2184\u20132186 (2004).","journal-title":"Neurology"},{"key":"7801_CR22","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1007\/s004300050097","volume":"187","author":"K Klaamas","year":"1999","unstructured":"Klaamas, K., Kurtenkov, O., Covacci, A., Lipping, A. & Wadstrom, T. Immune response to a recombinant fragment of the CagA protein of Helicobacter pylori in blood donors and patients with gastric cancer: relation to ABO(H) blood group phenotype, stage of the disease and tumor morphology. Medical microbiology and immunology \n                           187, 227\u2013232 (1999).","journal-title":"Medical microbiology and immunology"},{"key":"7801_CR23","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/PL00008209","volume":"436","author":"B Schmausser","year":"2000","unstructured":"Schmausser, B., Eck, M., Greiner, A., Kraus, M. & Muller-Hermelink, H. K. Mucosal humoral immune response to CagA shows a high prevalence in patients with gastric MALT-type lymphoma. Virchows Archiv: an international journal of pathology \n                           436, 115\u2013118 (2000).","journal-title":"Virchows Archiv: an international journal of pathology"},{"key":"7801_CR24","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1136\/jclinpath-2013-201743","volume":"67","author":"N Figura","year":"2014","unstructured":"Figura, N. et al. Cross-sectional study: CagA-positive Helicobacter pylori infection, acute coronary artery disease and systemic levels of B-type natriuretic peptide. Journal of clinical pathology \n                           67, 251\u2013257, doi:10.1136\/jclinpath-2013-201743 (2014).","journal-title":"Journal of clinical pathology"},{"key":"7801_CR25","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1111\/j.1523-5378.2007.00477.x","volume":"12","author":"M Kodama","year":"2007","unstructured":"Kodama, M. et al. Immune response to CagA protein is associated with improved platelet count after Helicobacter pylori eradication in patients with idiopathic thrombocytopenic purpura. Helicobacter \n                           12, 36\u201342, doi:10.1111\/j.1523-5378.2007.00477.x (2007).","journal-title":"Helicobacter"},{"key":"7801_CR26","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.1056\/NEJMoa0807646","volume":"359","author":"PM Ridker","year":"2008","unstructured":"Ridker, P. M. et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. The New England journal of medicine \n                           359, 2195\u20132207, doi:10.1056\/NEJMoa0807646 (2008).","journal-title":"The New England journal of medicine"},{"key":"7801_CR27","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1002\/ana.22366","volume":"69","author":"CH Polman","year":"2011","unstructured":"Polman, C. H. et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Annals of neurology \n                           69, 292\u2013302, doi:10.1002\/ana.22366 (2011).","journal-title":"Annals of neurology"},{"key":"7801_CR28","doi-asserted-by":"publisher","first-page":"2395","DOI":"10.1093\/brain\/aww173","volume":"139","author":"J Lorscheider","year":"2016","unstructured":"Lorscheider, J. et al. Defining secondary progressive multiple sclerosis. Brain: a journal of neurology \n                           139, 2395\u20132405, doi:10.1093\/brain\/aww173 (2016).","journal-title":"Brain: a journal of neurology"},{"key":"7801_CR29","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1111\/j.1742-1241.2005.00778.x","volume":"60","author":"M Sezikli","year":"2006","unstructured":"Sezikli, M. et al. Frequencies of serum antibodies to Helicobacter pylori CagA and VacA in a Turkish population with various gastroduodenal diseases. International journal of clinical practice \n                           60, 1239\u20131243, doi:10.1111\/j.1742-1241.2005.00778.x (2006).","journal-title":"International journal of clinical practice"},{"key":"7801_CR30","first-page":"153","volume":"36","author":"D Us","year":"2002","unstructured":"Us, D., Engin, D. & Hascelik, G. Evaluation of western blot methods for serologic diagnosis of Helicobacter pylori infections. Mikrobiyoloji bulteni \n                           36, 153\u2013160 (2002).","journal-title":"Mikrobiyoloji bulteni"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07801-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07801-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07801-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T08:23:03Z","timestamp":1671783783000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07801-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,11]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["7801"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-07801-9","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,11]]},"assertion":[{"value":"12 April 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 June 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Thomas Scheper & Wolfgang Meyer are employees of Euroimmun AG, Germany. All other authors do not have any conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"7929"}}