{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,6,3]],"date-time":"2023-06-03T13:11:00Z","timestamp":1685797860197},"reference-count":48,"publisher":"Akademiai Kiado Zrt.","issue":"40","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,10,1]]},"abstract":"<jats:p>A Crohn-betegs\u00e9g a termin\u00e1lis ileumot \u00e9s\/vagy a colont \u00e9rint\u0151 kr\u00f3nikus gyullad\u00e1ssal j\u00e1r\u00f3 senyveszt\u0151 betegs\u00e9g. Patogenezis\u00e9ben genetikai \u00e9s k\u00f6rnyezeti t\u00e9nyez\u0151k j\u00e1tszanak szerepet. \u00dajabban a molekul\u00e1ris genetika, genotipiz\u00e1l\u00e1si technol\u00f3gia, bioinformatika ter\u00e9n t\u00f6rt\u00e9nt el\u0151rehalad\u00e1s eredm\u00e9nyeit kombin\u00e1ltan alkalmazz\u00e1k az eg\u00e9sz genomra kiterjed\u0151 anal\u00edzis sor\u00e1n. Az \u00edgy felt\u00e1rt genetikai alter\u00e1ci\u00f3k betegs\u00e9ggel t\u00f6rt\u00e9n\u0151 t\u00e1rsul\u00e1s\u00e1nak vizsg\u00e1lata t\u00f6bb mint 30, a Crohn-betegs\u00e9ggel t\u00e1rsult fog\u00e9konys\u00e1gi g\u00e9n \u00e9s locus beazonos\u00edt\u00e1s\u00e1t \u00e9s kor\u00e1bban nem sejtett folyamatok Crohn-betegs\u00e9g patogenezis\u00e9ben j\u00e1tszott szerep\u00e9nek felt\u00e1r\u00e1s\u00e1t eredm\u00e9nyezte. A betegs\u00e9g szorosan t\u00e1rsul a mikrobi\u00e1lis molekul\u00e1ris mint\u00e1zatot felismer\u0151 receptorokat, f\u0151k\u00e9nt a NOD2 proteint, valamint a Vnt jel\u00fat Tcf4 transzkripci\u00f3s faktor\u00e1t (m\u00e1s n\u00e9ven TCFL2) \u00e9s az autophagi\u00e1t szab\u00e1lyoz\u00f3 ATG16L1 proteint k\u00f3dol\u00f3 g\u00e9neket \u00e9rint\u0151 polimorfizmusokkal. A sz\u00f3ban forg\u00f3 polimorfizmusok cs\u00f6kkent defenzintermel\u00e9ssel (defenzinel\u00e9gtelens\u00e9ggel) j\u00e1rnak, amely viszont a commensalis fl\u00f3ra \u00f6sszet\u00e9tel\u00e9ben v\u00e1ltoz\u00e1sokhoz, az intestinalis barrierfunkci\u00f3k defektus\u00e1hoz \u00e9s a ny\u00e1lkah\u00e1rtya bakteri\u00e1lis inv\u00e1zi\u00f3j\u00e1hoz vezet. A NOD2 \u00e9s ATG16L1 proteineket k\u00f3dol\u00f3 g\u00e9neket \u00e9rint\u0151 polimorfizmusoknak m\u00e1sik, \u00fajabban felismert k\u00f6vetkezm\u00e9nye, hogy a csonkolt NOD2 protein k\u00e9ptelen az autophagia induk\u00e1l\u00e1s\u00e1ra, tov\u00e1bb\u00e1 ez a protein csak\u00fagy, mint a mut\u00e1ns ATG16L1T300A protein, k\u00e9ptelen megc\u00e9lozni \u00e9s autophagosom\u00e1ba z\u00e1rva feldolgozni, majd a sejtb\u0151l kitakar\u00edtani a sejtekbe jutott mikrob\u00e1kat. K\u00f6vetkezm\u00e9nyesen a tart\u00f3san fennmarad\u00f3 alacsony szint\u0171 infekci\u00f3 miatt fell\u00e9p\u0151 adapt\u00edv immunv\u00e1lasz-reakci\u00f3 r\u00e9v\u00e9n kr\u00f3nikus gyullad\u00e1s, sz\u00f6vetk\u00e1rosod\u00e1s \u00e9s a betegs\u00e9g klinikai t\u00fcnetei alakulnak ki. Ezek f\u00e9ny\u00e9ben \u00fagy tekinthet\u0151, hogy a Crohn-betegs\u00e9g kialakul\u00e1s\u00e1t a genetikailag fog\u00e9kony egyedekben a velesz\u00fcletett immunv\u00e9dekez\u00e9s defektusa okozza vagy legal\u00e1bbis az ind\u00edtja el, amelyhez a b\u00e9lh\u00e1msejtekbe jutott \u00e9s ott perziszt\u00e1l\u00f3 intestinalis mikrob\u00e1kkal szemben fell\u00e9p\u0151 felfokozott adapt\u00edv immunv\u00e1lasz-reakci\u00f3val kapcsolatos gyullad\u00e1s t\u00e1rsul. Ilyen k\u00f6r\u00fclm\u00e9nyek k\u00f6z\u00f6tt a ter\u00e1pi\u00e1s c\u00e9l\u00fa intervenci\u00f3nak feltehet\u0151en ink\u00e1bb a velesz\u00fcletett immunv\u00e1lasz er\u0151s\u00edt\u00e9s\u00e9re, mintsem csak az adapt\u00edv immunv\u00e1lasz-reakci\u00f3k elnyom\u00e1s\u00e1ra kellene ir\u00e1nyulnia. Orv. Hetil., 2010,<jats:italic>40,<\/jats:italic>1645\u20131655.<\/jats:p>","DOI":"10.1556\/oh.2010.28942","type":"journal-article","created":{"date-parts":[[2010,9,23]],"date-time":"2010-09-23T01:05:21Z","timestamp":1285203921000},"page":"1645-1655","source":"Crossref","is-referenced-by-count":0,"title":["Barrier- and autophagic functions of the intestinal epithelia: role of disturbances in the pathogenesis of Crohn\u2019s disease"],"prefix":"10.1556","volume":"151","author":[{"given":"K\u00e1roly","family":"Lapis","sequence":"first","affiliation":[{"name":"1 Semmelweis Egyetem, \u00c1ltal\u00e1nos Orvostudom\u00e1nyi Kar I. 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Gastroenterol."},{"key":"atypb6","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1159\/000228554","volume":"27","year":"2009","journal-title":"Dig. Dis."},{"key":"atypb7","first-page":"1284","volume":"10","year":"2007","journal-title":"Inflamm. Bowel Dis."},{"key":"atypb8","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1159\/000233282","volume":"27","year":"2009","journal-title":"Dig. Dis."},{"key":"atypb10","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1189\/jlb.0609382","volume":"87","year":"2010","journal-title":"J. Leuk. Biol."},{"key":"atypb11","first-page":"189","volume":"27","year":"2009","journal-title":"Immunological Reviews"},{"key":"atypb12","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1097\/MOG.0b013e3280105a38","volume":"23","year":"2007","journal-title":"Curr. Opin. Gastroenterol."},{"key":"atypb13","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/ismej.2007.52","volume":"1","year":"2007","journal-title":"ISME J."},{"key":"atypb14","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1097\/00042737-200306000-00008","volume":"15","year":"2003","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"atypb15","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1136\/gut.2006.118646","volume":"56","year":"2007","journal-title":"Gut"},{"key":"atypb16","first-page":"406","volume":"2","year":"2005","journal-title":"Nat. Clin. Pract. Gastroenterol. Hepatol."},{"key":"atypb17","doi-asserted-by":"crossref","first-page":"5499","DOI":"10.3748\/wjg.14.5499","volume":"14","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"atypb18","doi-asserted-by":"crossref","first-page":"702","DOI":"10.2353\/ajpath.2008.070755","volume":"172","year":"2008","journal-title":"Am. J. Pathol."},{"key":"atypb19","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1038\/379821a0","volume":"379","year":"1996","journal-title":"Nature"},{"key":"atypb20","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/35079114","volume":"411","year":"2001","journal-title":"Nature"},{"key":"atypb21","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1136\/gut.2003.032805","volume":"53","year":"2004","journal-title":"Gut"},{"key":"atypb22","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1016\/j.micinf.2007.01.016","volume":"9","year":"2007","journal-title":"Microbes and Infections"},{"key":"atypb23","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ijmm.2009.08.007","volume":"300","year":"2010","journal-title":"Int. J. Med. Microbiol."},{"key":"atypb24","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1111\/j.1399-0039.2008.01049.x","volume":"71","year":"2008","journal-title":"Tissue Antigens"},{"key":"atypb25","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1136\/gut.2007.142588","volume":"57","year":"2008","journal-title":"Gut"},{"key":"atypb26","first-page":"882","volume":"58","year":"2009","journal-title":"Gut"},{"key":"atypb27","first-page":"883","volume":"58","year":"2009","journal-title":"Gut"},{"key":"atypb28","doi-asserted-by":"crossref","first-page":"5550","DOI":"10.3748\/wjg.v12.i34.5550","volume":"12","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"atypb29","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1016\/j.dld.2007.09.003","volume":"39","year":"2007","journal-title":"Dig. Liver Disease"},{"key":"atypb30","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1002\/ibd.20146","volume":"13","year":"2007","journal-title":"Inflamm. Bowel Dis."},{"key":"atypb31","doi-asserted-by":"crossref","first-page":"3109","DOI":"10.4049\/jimmunol.179.5.3109","volume":"179","year":"2007","journal-title":"J. Immunol."},{"key":"atypb32","doi-asserted-by":"crossref","first-page":"e4496","DOI":"10.1371\/journal.pone.0004496","volume":"4","year":"2009","journal-title":"PLoS ONE"},{"key":"atypb33","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1038\/ng2061","volume":"39","year":"2007","journal-title":"Nat. Genet."},{"key":"atypb34","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1159\/000228557","volume":"27","year":"2009","journal-title":"Dig. Dis."},{"key":"atypb35","first-page":"141","volume":"335","year":"2009","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"atypb36","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1056\/NEJMcibr0810347","volume":"360","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"atypb37","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/ni.1823","volume":"11","year":"2010","journal-title":"Nature Immunol."},{"key":"atypb38","first-page":"409","volume":"3","year":"2010","journal-title":"Autophagy"},{"key":"atypb39","doi-asserted-by":"crossref","first-page":"6718","DOI":"10.4049\/jimmunol.163.12.6718","volume":"163","year":"1999","journal-title":"J. Immunol."},{"key":"atypb40","first-page":"42","volume":"86","year":"2005","journal-title":"Chem. Immunol. Allergy"},{"key":"atypb41","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1086\/505915","volume":"79","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"atypb42","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1038\/ajg.2009.582","volume":"105","year":"2010","journal-title":"Am. J. Gastroenterol."},{"key":"atypb43","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/ajg.2009.573","volume":"105","year":"2010","journal-title":"Am. J. Gastroenterol."},{"key":"atypb44","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1080\/00365520701682615","volume":"43","year":"2008","journal-title":"Scand J. Gastroenterol."},{"key":"atypb45","doi-asserted-by":"crossref","first-page":"176","DOI":"10.3748\/wjg.v16.i2.176","volume":"16","year":"2010","journal-title":"World J. Gastroenterol."},{"key":"atypb46","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S0161-5890(03)00157-3","volume":"40","year":"2003","journal-title":"Mol. Immunol."},{"key":"atypb47","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1159\/000235851","volume":"27","year":"2009","journal-title":"Dig. Dis."},{"key":"atypb48","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1159\/000233283","volume":"27","year":"2009","journal-title":"Dig. 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