{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T12:37:57Z","timestamp":1790944677421,"version":"4.1.0"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,17]],"date-time":"2017-08-17T00:00:00Z","timestamp":1502928000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,17]],"date-time":"2017-08-17T00:00:00Z","timestamp":1502928000000},"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>\n                  <jats:p>This prospective study investigates whether measurement of plasma intestinal-fatty acid binding protein (I-FABP), a sensitive marker for small intestinal epithelial damage, improves non-invasive diagnosing of celiac disease (CD), and whether I-FABP levels are useful to evaluate mucosal healing in patients on a gluten-free diet (GFD). Ninety children with elevated tTG-IgA titres and HLA-DQ2\/DQ8 positivity were included (study group). Duodenal biopsies were taken, except in those fulfilling the ESPGHAN criteria. Plasma I-FABP levels and tTG-IgA titres were assessed sequentially during six months of follow-up. Eighty children with normal tTG-IgA titres served as control group. In 61\/90 (67.8%) of the children in the study group an increased I-FABP level was found; in all these children CD diagnosis was confirmed. Interestingly, in 14\/30 (46.7%) children with slightly elevated tTG-IgA titres (&lt;10x upper limit of normal), an increased I-FABP level was found. In all these children the diagnosis of CD was confirmed histologically. After gluten elimination for six weeks I-FABP levels had decreased towards levels in the control group. Measurement of plasma I-FABP, in addition to tTG-IgA, EMA-IgA and HLAtyping, enables non-invasive diagnosing of CD in a substantial number of children, and might therefore be of value in the diagnostic approach of CD.<\/jats:p>","DOI":"10.1038\/s41598-017-07242-4","type":"journal-article","created":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T11:17:42Z","timestamp":1502450262000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["Progress towards non-invasive diagnosis and follow-up of celiac disease in children; a prospective multicentre study to the usefulness of plasma I-FABP"],"prefix":"10.1038","volume":"7","author":[{"given":"M. P. M.","family":"Adriaanse","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Mubarak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. G.","family":"Riedl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. J. W.","family":"Ten Kate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. G. M. C.","family":"Damoiseaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. A.","family":"Buurman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. H. J.","family":"Houwen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. C. E.","family":"Vreugdenhil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Celiac Disease Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. C. G.","family":"Beeren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. M. L.","family":"van Dael","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. C.","family":"Engelberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. H.","family":"Hanekom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. J. E.","family":"Hendriks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Hubregtse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Jonkers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. S.","family":"Kapteijns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. M.","family":"Kerkvliet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. M.","family":"van den Neucker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Potgieter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Raaijmakers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. P. R.","family":"Rosias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. J. H. M.","family":"Stouthart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. M. V. M.","family":"Theunissen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. M.","family":"van Wering","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. B. G.","family":"Wijnands","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,17]]},"reference":[{"key":"7242_CR1","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1056\/NEJMra071600","volume":"357","author":"PH Green","year":"2007","unstructured":"Green, P. H. & Cellier, C. Celiac disease. N. Engl. J. Med. \n                           357, 1731\u201343 (2007).","journal-title":"N. Engl. J. Med."},{"key":"7242_CR2","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1097\/MPG.0b013e31821a23d0","volume":"54","author":"S Husby","year":"2012","unstructured":"Husby, S. et al. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J. Pediatr. Gastroenterol. Nutr. \n                           54, 136\u201360 (2012).","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"7242_CR3","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.3109\/00365521.2011.589471","volume":"46","author":"A Mubarak","year":"2011","unstructured":"Mubarak, A., Nikkels, P., Houwen, R. & Ten Kate, F. Reproducibility of the histological diagnosis of celiac disease. Scand. J. Gastroenterol. \n                           46, 1065\u201373 (2011).","journal-title":"Scand. J. Gastroenterol."},{"key":"7242_CR4","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1136\/jclinpath-2011-200372","volume":"65","author":"C Arguelles-Grande","year":"2012","unstructured":"Arguelles-Grande, C., Tennyson, C. A., Lewis, S. K., Green, P. H. & Bhagat, G. Variability in small bowel histopathology reporting between different pathology practice settings: impact on the diagnosis of coeliac disease. J. Clin. Pathol. \n                           65, 242\u20137 (2012).","journal-title":"J. Clin. Pathol."},{"key":"7242_CR5","doi-asserted-by":"publisher","first-page":"2103","DOI":"10.1038\/ajg.2010.153","volume":"105","author":"A Ravelli","year":"2010","unstructured":"Ravelli, A. et al. How patchy is patchy villous atrophy?: distribution pattern of histological lesions in the duodenum of children with celiac disease. Am. J. Gastroenterol. \n                           105, 2103\u201310 (2010).","journal-title":"Am. J. Gastroenterol."},{"key":"7242_CR6","doi-asserted-by":"publisher","first-page":"427","DOI":"10.3109\/00365521.2015.1101486","volume":"51","author":"C Monten","year":"2016","unstructured":"Monten, C. et al. Scand. J. Gastroenterol. \n                           51, 427\u2013433 (2016).","journal-title":"Scand. J. Gastroenterol."},{"key":"7242_CR7","doi-asserted-by":"publisher","first-page":"S135","DOI":"10.1053\/j.gastro.2005.02.025","volume":"128","author":"MM Pietzak","year":"2005","unstructured":"Pietzak, M. M. Follow-up of patients with celiac disease: achieving compliance with treatment. Gastroenterology. \n                           128, S135\u201341 (2005).","journal-title":"Gastroenterology."},{"key":"7242_CR8","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1111\/j.1572-0241.2000.01838.x","volume":"95","author":"W Dickey","year":"2000","unstructured":"Dickey, W., Hughes, D. F. & McMillan, S. A. Disappearance of endomysial antibodies in treated celiac disease does not indicate histological recovery. Am. J. Gastroenterol. \n                           95, 712\u2013714 (2000).","journal-title":"Am. J. Gastroenterol."},{"key":"7242_CR9","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1111\/j.1365-2036.2007.03501.x","volume":"26","author":"DA Leffler","year":"2007","unstructured":"Leffler, D. A. et al. A prospective comparative study of five measures of gluten-free diet adherence in adults with coeliac disease. Aliment. Pharmacol. Ther. \n                           26, 1227\u201335 (2007).","journal-title":"Aliment. Pharmacol. Ther."},{"key":"7242_CR10","doi-asserted-by":"crossref","unstructured":"Lourdes Moreno, M., Rodriguez-Herrera, A., Sousa, C. & Comino, I. Biomarkers to monitor gluten-free diet compliance in celiac patients. Nutrients 9, doi:10.3390 (2017).","DOI":"10.3390\/nu9010046"},{"key":"7242_CR11","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1053\/gast.1996.v110.pm8566578","volume":"110","author":"T Kanda","year":"1996","unstructured":"Kanda, T. et al. Intestinal fatty acid-binding protein is a useful diagnostic marker for mesenteric infarction in humans. Gastroenterology. \n                           110, 339\u201343 (1996).","journal-title":"Gastroenterology."},{"key":"7242_CR12","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.1097\/SLA.0b013e3181d778c4","volume":"251","author":"G Thuijls","year":"2010","unstructured":"Thuijls, G. et al. Non-invasive markers for early diagnosis and determination of the severity of necrotizing enterocolitis. Ann. Surg. \n                           251, 1174\u201380 (2010).","journal-title":"Ann. Surg."},{"key":"7242_CR13","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1097\/SLA.0b013e318207a767","volume":"253","author":"G Thuijls","year":"2011","unstructured":"Thuijls, G. et al. Early diagnosis of intestinal ischemia using urinary and plasma fatty acid binding proteins. Ann. Surg. \n                           253, 303\u20138 (2011).","journal-title":"Ann. Surg."},{"key":"7242_CR14","doi-asserted-by":"publisher","first-page":"e0121336","DOI":"10.1371\/journal.pone.0121336","volume":"10","author":"M Schurink","year":"2015","unstructured":"Schurink, M. et al. Intestinal-fatty acid binding protein as a diagnostic marker for complicated and uncomplicated necrotizing enterocolitis: a prospective cohort study. Plos One. \n                           10, e0121336 (2015).","journal-title":"Plos One."},{"key":"7242_CR15","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1007\/s00418-009-0608-y","volume":"132","author":"E Levy","year":"2009","unstructured":"Levy, E. et al. Localization, function and regulation of the two intestinal fatty acid-binding protein types. Histochem. Cell. Biol. \n                           132, 351\u201367 (2009).","journal-title":"Histochem. Cell. Biol."},{"key":"7242_CR16","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1097\/MCG.0b013e31819194b0","volume":"43","author":"JP Derikx","year":"2009","unstructured":"Derikx, J. P. et al. A pilot study on the noninvasive evaluation of intestinal damage in celiac disease using I-FABP and L-FABP. J. Clin. Gastroenterol. \n                           43, 727\u201333 (2009).","journal-title":"J. Clin. Gastroenterol."},{"key":"7242_CR17","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.3109\/00365521.2011.627447","volume":"46","author":"AC Vreugdenhil","year":"2011","unstructured":"Vreugdenhil, A. C. et al. Additional value of serum I-FABP levels for evaluating celiac disease activity in children. Scand. J. Gastroenterol. \n                           46, 1435\u201341 (2011).","journal-title":"Scand. J. Gastroenterol."},{"key":"7242_CR18","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1111\/apt.12194","volume":"37","author":"MP Adriaanse","year":"2013","unstructured":"Adriaanse, M. P. et al. Serum I-FABP as marker for enterocyte damage in coeliac disease and its relation to villous atrophy and circulating autoantibodies. Aliment. Pharmacol. Ther. \n                           37, 482\u201390 (2013).","journal-title":"Aliment. Pharmacol. Ther."},{"key":"7242_CR19","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.regpep.2007.12.002","volume":"147","author":"A Wiercinska-Drapalo","year":"2008","unstructured":"Wiercinska-Drapalo, A., Jaroszewicz, J., Siwak, E., Pogorzelska, J. & Prokopowicz, D. Intestinal fatty acid binding protein (I-FABP) as a possible biomarker of ileitis in patients with ulcerative colitis. Regul. Pept. \n                           147, 25\u20138 (2008).","journal-title":"Regul. Pept."},{"key":"7242_CR20","doi-asserted-by":"crossref","unstructured":"Revised criteria for diagnosis of coeliac disease. Report of Working Group of European Society of Paediatric Gastroenterology and Nutrition. Arch. Dis. Child. 65, 909\u201311 (1990).","DOI":"10.1136\/adc.65.8.909"},{"key":"7242_CR21","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1016\/j.humimm.2010.09.010","volume":"71","author":"CE Voorter","year":"2010","unstructured":"Voorter, C. E., Lauterbach, N. & Tilanus, M. G. Inactivation of a functional HLA-A gene: a 4-kb deletion turns HLA-A*24 into a pseudogene. Hum. Immunol. \n                           71, 1197\u2013202 (2010).","journal-title":"Hum. Immunol."},{"key":"7242_CR22","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1007\/978-1-4614-9437-9_7","volume":"1109","author":"CE Voorter","year":"2014","unstructured":"Voorter, C. E., Palusci, F. & Tilanus, M. G. Sequence-based typing of HLA: an improved group-specific full-length gene sequencing approach. Methods Mol. Biol. \n                           1109, 101\u201314 (2014).","journal-title":"Methods Mol. Biol."},{"key":"7242_CR23","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/0016-5085(92)91819-P","volume":"102","author":"MN Marsh","year":"1992","unstructured":"Marsh, M. N. Gluten, major histocompatibility complex, and the small intestine. A molecular and immunobiologic approach to the spectrum of gluten sensitivity (\u2018celiac sprue\u2019). Gastroenterology. \n                           102, 330\u201354 (1992).","journal-title":"Gastroenterology."},{"key":"7242_CR24","doi-asserted-by":"publisher","first-page":"888","DOI":"10.1111\/j.1572-0241.1999.983_f.x","volume":"94","author":"K Rostami","year":"1999","unstructured":"Rostami, K. et al. Sensitivity of antiendomysium and antigliadin antibodies in untreated celiac disease: disappointing in clinical practice. Am. J. Gastroenterol. \n                           94, 888\u201394 (1999).","journal-title":"Am. J. Gastroenterol."},{"key":"7242_CR25","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1034\/j.1600-0463.2000.d01-72.x","volume":"108","author":"B Weile","year":"2000","unstructured":"Weile, B., Hansen, B. F., Hagerstrand, I., Hansen, J. P. & Krasilnikoff, P. A. Interobserver variation in diagnosing coeliac disease. A joint study by Danish and Swedish pathologists. APMIS. \n                           108, 380\u20134 (2000).","journal-title":"APMIS."},{"key":"7242_CR26","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1136\/gutjnl-2012-302196","volume":"62","author":"DA Leffler","year":"2012","unstructured":"Leffler, D. A. et al. Kinetics of the histological, serological and symptomatic responses to gluten challenge in adults with coeliac disease. Gut. \n                           62, 996\u20131004 (2012).","journal-title":"Gut."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07242-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07242-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07242-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T03:54:21Z","timestamp":1671767661000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07242-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,17]]},"references-count":26,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["7242"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-07242-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,17]]},"assertion":[{"value":"21 February 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 May 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 August 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"8671"}}