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Ingesting gluten elevates circulating interleukin (IL)\u20102, IL\u20108 and IL\u201010\u00a0in CD patients on a GFD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We tested whether cytokine release after gluten ingestion differentiates patients with CD from those with self\u2010reported gluten sensitivity (SR\u2010GS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Australian patients with CD (<jats:italic>n<\/jats:italic> \u2009=\u200926) and SR\u2010GS (<jats:italic>n<\/jats:italic> \u2009=\u200918) on a GFD consumed bread (estimated gluten 6\u2009g). Serum at baseline and at 3 and 4\u2009h was tested for IL\u20102, IL\u20108 and IL\u201010. Separately, Norwegian SR\u2010GS patients (<jats:italic>n<\/jats:italic> \u2009=\u200949) had plasma cytokine assessment at baseline and at 2, 4 and 6\u2009h after food bars containing gluten (5.7\u2009g), fructan or placebo in a previous double\u2010blind crossover study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Gluten significantly elevated serum IL\u20102, IL\u20108 and IL\u201010 at 3 and 4\u2009h in patients with CD but not SR\u2010GS. The highest median fold\u2010change from baseline at 4\u2009h was for IL\u20102 (8.06, IQR: 1.52\u201324.0; <jats:italic>P<\/jats:italic> \u2009&lt;\u20090.0001, Wilcoxon test). The two SR\u2010GS cohorts included only one (1.5%) confirmed IL\u20102 responder, and cytokine responses to fructan and placebo were no different to gluten. Overall, cytokine release after gluten was present in 22 (85%) CD participants, but 2 of the 4\u00a0non\u2010responders remained clinically well after 1 y on an unrestricted diet. Hence, cytokine release occurred in 22 (92%) of 24 \u2018verified\u2019 CD participants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Gluten challenge with high\u2010sensitivity cytokine assessment differentiates CD from SR\u2010GS in patients on a GFD and identifies patients likely to tolerate gluten reintroduction. Systemic cytokine release indicating early immune activation by gluten in CD individuals cannot be detected in SR\u2010GS individuals.<\/jats:p><\/jats:sec>","DOI":"10.1177\/2050640619874173","type":"journal-article","created":{"date-parts":[[2019,9,4]],"date-time":"2019-09-04T01:45:40Z","timestamp":1567561540000},"page":"108-118","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":45,"title":["Cytokine release after gluten ingestion differentiates coeliac disease from self\u2010reported gluten sensitivity"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7687-9654","authenticated-orcid":false,"given":"Jason A","family":"Tye\u2010Din","sequence":"first","affiliation":[{"name":"Immunology Division Department of Medical Biology Walter and Eliza Hall Institute of Medical Research University of Melbourne Australia"},{"name":"Murdoch Children\u2019s Research Institute Parkville Australia"},{"name":"Department of Gastroenterology Royal Melbourne Hospital Parkville Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gry I","family":"Skodje","sequence":"additional","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre University of Oslo Oslo Norway"},{"name":"Department of Nutrition Institute of Basic Medical Sciences University of Oslo Oslo Norway"},{"name":"Unit for Clinical Nutrition Division of Cancer Medicine Oslo University Hospital Rikshospitalet Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas K","family":"Sarna","sequence":"additional","affiliation":[{"name":"KG Jebsen Coeliac Disease Research Centre University of Oslo Oslo Norway"},{"name":"Department of Immunology Oslo University Hospital Rikshospitalet Oslo Norway"},{"name":"Department of Gastroenterology Oslo University Hospital Rikshospitalet Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L","family":"Dzuris","sequence":"additional","affiliation":[{"name":"ImmusanT Inc. 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