Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease
Celiac disease (CeD), caused by immune reactions to cereal gluten, is treated with gluten -elimination diets. Within hours of gluten exposure, either perorally or extraorally by intradermal injection, treated patients experience gastrointestinal symptoms. To test whether gluten exposure leads to sys...
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| Veröffentlicht in: | Science advances 2019-08, Vol.5 (8), p.eaaw7756-eaaw7756 |
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| creator | Goel, Gautam Tye-Din, Jason A Qiao, Shuo-Wang Russell, Amy K Mayassi, Toufic Ciszewski, Cezary Sarna, Vikas K Wang, Suyue Goldstein, Kaela E Dzuris, John L Williams, Leslie J Xavier, Ramnik J Lundin, Knut E A Jabri, Bana Sollid, Ludvig M Anderson, Robert P |
| description | Celiac disease (CeD), caused by immune reactions to cereal gluten, is treated with gluten -elimination diets. Within hours of gluten exposure, either perorally or extraorally by intradermal injection, treated patients experience gastrointestinal symptoms. To test whether gluten exposure leads to systemic cytokine production time -related to symptoms, series of multiplex cytokine measurements were obtained in CeD patients after gluten challenge. Peptide injection elevated at least 15 plasma cytokines, with IL-2, IL-8, and IL-10 being most prominent (fold-change increase at 4 hours of 272, 11, and 1.2, respectively). IL-2 and IL-8 were the only cytokines elevated at 2 hours, preceding onset of symptoms. After gluten ingestion, IL-2 was the earliest and most prominent cytokine (15-fold change at 4 hours). Supported by studies of patient-derived gluten-specific T cell clones and primary lymphocytes, our observations indicate that gluten-specific CD4
T cells are rapidly reactivated by antigen -exposure likely causing CeD-associated gastrointestinal symptoms. |
| doi_str_mv | 10.1126/sciadv.aaw7756 |
| format | Article |
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T cells are rapidly reactivated by antigen -exposure likely causing CeD-associated gastrointestinal symptoms.</description><identifier>ISSN: 2375-2548</identifier><identifier>EISSN: 2375-2548</identifier><identifier>DOI: 10.1126/sciadv.aaw7756</identifier><identifier>PMID: 31457091</identifier><language>eng</language><publisher>United States: American Association for the Advancement of Science</publisher><subject>Adult ; Aged ; CD4-Positive T-Lymphocytes - classification ; CD4-Positive T-Lymphocytes - metabolism ; Celiac Disease - immunology ; Celiac Disease - metabolism ; Celiac Disease - pathology ; Cytokines - blood ; Double-Blind Method ; Female ; Genotype ; Glutens - administration & dosage ; Glutens - adverse effects ; HLA Antigens - genetics ; Humans ; Immunology ; Interleukin-10 - blood ; Interleukin-2 - blood ; Interleukin-8 - blood ; Male ; Middle Aged ; Placebo Effect ; SciAdv r-articles ; Vomiting - etiology ; Young Adult</subject><ispartof>Science advances, 2019-08, Vol.5 (8), p.eaaw7756-eaaw7756</ispartof><rights>info:eu-repo/semantics/openAccess</rights><rights>Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). 2019 The Authors</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c414t-841046bfa1b336fa8c92ff85b466ff9ccdcb31061bf2bfef7ca81c02ae07a8d63</citedby><cites>FETCH-LOGICAL-c414t-841046bfa1b336fa8c92ff85b466ff9ccdcb31061bf2bfef7ca81c02ae07a8d63</cites><orcidid>0000-0002-5458-1352 ; 0000-0003-1713-5545 ; 0000-0001-7427-4424 ; 0000-0001-8860-704X ; 0000-0002-0046-8426 ; 0000-0002-0764-7267 ; 0000-0002-0034-2807 ; 0000-0003-4054-1074 ; 0000-0002-5630-5167 ; 0000-0001-7687-9654 ; 0000-0002-0578-1497 ; 0000-0002-4716-135X ; 0000-0002-4982-986X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685723/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685723/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,26567,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31457091$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Goel, Gautam</creatorcontrib><creatorcontrib>Tye-Din, Jason A</creatorcontrib><creatorcontrib>Qiao, Shuo-Wang</creatorcontrib><creatorcontrib>Russell, Amy K</creatorcontrib><creatorcontrib>Mayassi, Toufic</creatorcontrib><creatorcontrib>Ciszewski, Cezary</creatorcontrib><creatorcontrib>Sarna, Vikas K</creatorcontrib><creatorcontrib>Wang, Suyue</creatorcontrib><creatorcontrib>Goldstein, Kaela E</creatorcontrib><creatorcontrib>Dzuris, John L</creatorcontrib><creatorcontrib>Williams, Leslie J</creatorcontrib><creatorcontrib>Xavier, Ramnik J</creatorcontrib><creatorcontrib>Lundin, Knut E A</creatorcontrib><creatorcontrib>Jabri, Bana</creatorcontrib><creatorcontrib>Sollid, Ludvig M</creatorcontrib><creatorcontrib>Anderson, Robert P</creatorcontrib><title>Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease</title><title>Science advances</title><addtitle>Sci Adv</addtitle><description>Celiac disease (CeD), caused by immune reactions to cereal gluten, is treated with gluten -elimination diets. Within hours of gluten exposure, either perorally or extraorally by intradermal injection, treated patients experience gastrointestinal symptoms. To test whether gluten exposure leads to systemic cytokine production time -related to symptoms, series of multiplex cytokine measurements were obtained in CeD patients after gluten challenge. Peptide injection elevated at least 15 plasma cytokines, with IL-2, IL-8, and IL-10 being most prominent (fold-change increase at 4 hours of 272, 11, and 1.2, respectively). IL-2 and IL-8 were the only cytokines elevated at 2 hours, preceding onset of symptoms. After gluten ingestion, IL-2 was the earliest and most prominent cytokine (15-fold change at 4 hours). Supported by studies of patient-derived gluten-specific T cell clones and primary lymphocytes, our observations indicate that gluten-specific CD4
T cells are rapidly reactivated by antigen -exposure likely causing CeD-associated gastrointestinal symptoms.</description><subject>Adult</subject><subject>Aged</subject><subject>CD4-Positive T-Lymphocytes - classification</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>Celiac Disease - immunology</subject><subject>Celiac Disease - metabolism</subject><subject>Celiac Disease - pathology</subject><subject>Cytokines - blood</subject><subject>Double-Blind Method</subject><subject>Female</subject><subject>Genotype</subject><subject>Glutens - administration & dosage</subject><subject>Glutens - adverse effects</subject><subject>HLA Antigens - genetics</subject><subject>Humans</subject><subject>Immunology</subject><subject>Interleukin-10 - blood</subject><subject>Interleukin-2 - blood</subject><subject>Interleukin-8 - blood</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Placebo Effect</subject><subject>SciAdv r-articles</subject><subject>Vomiting - etiology</subject><subject>Young Adult</subject><issn>2375-2548</issn><issn>2375-2548</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>3HK</sourceid><recordid>eNpVkc1vGyEQxVHVqonSXHtsOPZil49dwJdKlZW0lSLlkihHNMuCQ8KCA9iV__tg2YnSE4N485s3PIS-UjKnlIkfxXgYt3OAf1L24gM6ZVz2M9Z36uO7-gSdl_JICKGdED1dfEYnnHa9JAt6iu6Xu5qefLQ422ChWAxxxCsoNScfqy3VRwi47KZ1TVPB4KrNeBU21UZsHiAEG1cW-3axwYPBoy97zBf0yUEo9vx4nqG7q8vb5Z_Z9c3vv8tf1zPT0a7OVEdJJwYHdOBcOFBmwZxT_dCsOrcwZjQDp0TQwbHBWScNKGoIA0skqFHwM_TzwF1vhsmOxsaaIeh19hPknU7g9f8v0T_oVdpqIVQvGW-AiwPAZL9fVseUQVOieqalpFw1xffjiJyeN-1H9ORL2zZAtGlTNGOKquaXkyadv8JSKdm6NyOU6H1k-hCZPkbWGr69t_8mfw2IvwDD2JY7</recordid><startdate>20190801</startdate><enddate>20190801</enddate><creator>Goel, Gautam</creator><creator>Tye-Din, Jason A</creator><creator>Qiao, Shuo-Wang</creator><creator>Russell, Amy K</creator><creator>Mayassi, Toufic</creator><creator>Ciszewski, Cezary</creator><creator>Sarna, Vikas K</creator><creator>Wang, Suyue</creator><creator>Goldstein, Kaela E</creator><creator>Dzuris, John L</creator><creator>Williams, Leslie J</creator><creator>Xavier, Ramnik J</creator><creator>Lundin, Knut E A</creator><creator>Jabri, Bana</creator><creator>Sollid, Ludvig M</creator><creator>Anderson, Robert P</creator><general>American Association for the Advancement of Science</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>3HK</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-5458-1352</orcidid><orcidid>https://orcid.org/0000-0003-1713-5545</orcidid><orcidid>https://orcid.org/0000-0001-7427-4424</orcidid><orcidid>https://orcid.org/0000-0001-8860-704X</orcidid><orcidid>https://orcid.org/0000-0002-0046-8426</orcidid><orcidid>https://orcid.org/0000-0002-0764-7267</orcidid><orcidid>https://orcid.org/0000-0002-0034-2807</orcidid><orcidid>https://orcid.org/0000-0003-4054-1074</orcidid><orcidid>https://orcid.org/0000-0002-5630-5167</orcidid><orcidid>https://orcid.org/0000-0001-7687-9654</orcidid><orcidid>https://orcid.org/0000-0002-0578-1497</orcidid><orcidid>https://orcid.org/0000-0002-4716-135X</orcidid><orcidid>https://orcid.org/0000-0002-4982-986X</orcidid></search><sort><creationdate>20190801</creationdate><title>Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease</title><author>Goel, Gautam ; 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Within hours of gluten exposure, either perorally or extraorally by intradermal injection, treated patients experience gastrointestinal symptoms. To test whether gluten exposure leads to systemic cytokine production time -related to symptoms, series of multiplex cytokine measurements were obtained in CeD patients after gluten challenge. Peptide injection elevated at least 15 plasma cytokines, with IL-2, IL-8, and IL-10 being most prominent (fold-change increase at 4 hours of 272, 11, and 1.2, respectively). IL-2 and IL-8 were the only cytokines elevated at 2 hours, preceding onset of symptoms. After gluten ingestion, IL-2 was the earliest and most prominent cytokine (15-fold change at 4 hours). Supported by studies of patient-derived gluten-specific T cell clones and primary lymphocytes, our observations indicate that gluten-specific CD4
T cells are rapidly reactivated by antigen -exposure likely causing CeD-associated gastrointestinal symptoms.</abstract><cop>United States</cop><pub>American Association for the Advancement of Science</pub><pmid>31457091</pmid><doi>10.1126/sciadv.aaw7756</doi><orcidid>https://orcid.org/0000-0002-5458-1352</orcidid><orcidid>https://orcid.org/0000-0003-1713-5545</orcidid><orcidid>https://orcid.org/0000-0001-7427-4424</orcidid><orcidid>https://orcid.org/0000-0001-8860-704X</orcidid><orcidid>https://orcid.org/0000-0002-0046-8426</orcidid><orcidid>https://orcid.org/0000-0002-0764-7267</orcidid><orcidid>https://orcid.org/0000-0002-0034-2807</orcidid><orcidid>https://orcid.org/0000-0003-4054-1074</orcidid><orcidid>https://orcid.org/0000-0002-5630-5167</orcidid><orcidid>https://orcid.org/0000-0001-7687-9654</orcidid><orcidid>https://orcid.org/0000-0002-0578-1497</orcidid><orcidid>https://orcid.org/0000-0002-4716-135X</orcidid><orcidid>https://orcid.org/0000-0002-4982-986X</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; NORA - Norwegian Open Research Archives; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Adult Aged CD4-Positive T-Lymphocytes - classification CD4-Positive T-Lymphocytes - metabolism Celiac Disease - immunology Celiac Disease - metabolism Celiac Disease - pathology Cytokines - blood Double-Blind Method Female Genotype Glutens - administration & dosage Glutens - adverse effects HLA Antigens - genetics Humans Immunology Interleukin-10 - blood Interleukin-2 - blood Interleukin-8 - blood Male Middle Aged Placebo Effect SciAdv r-articles Vomiting - etiology Young Adult |
| title | Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease |
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