Deep sequencing of blood and gut T-cell receptor beta-chains reveals gluten-induced immune signatures in celiac disease

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dc.contributor University of Helsinki, Research Programs Unit en
dc.contributor University of Helsinki, Research Programs Unit en
dc.contributor University of Helsinki, Medicum en
dc.contributor University of Helsinki, Research Programs Unit en
dc.contributor University of Helsinki, Research Programs Unit en
dc.contributor.author Yohannes, Dawit A.
dc.contributor.author Freitag, Tobias L.
dc.contributor.author de Kauwe, Andrea
dc.contributor.author Kaukinen, Katri
dc.contributor.author Kurppa, Kalle
dc.contributor.author Wacklin, Pirjo
dc.contributor.author Mäki, Markku
dc.contributor.author Arstila, T. Petteri
dc.contributor.author Anderson, Robert P.
dc.contributor.author Greco, Dario
dc.contributor.author Saavalainen, Päivi
dc.date.accessioned 2018-01-18T11:07:00Z
dc.date.available 2018-01-18T11:07:00Z
dc.date.issued 2017-12-21
dc.identifier.citation Yohannes , D A , Freitag , T L , de Kauwe , A , Kaukinen , K , Kurppa , K , Wacklin , P , Mäki , M , Arstila , T P , Anderson , R P , Greco , D & Saavalainen , P 2017 , ' Deep sequencing of blood and gut T-cell receptor beta-chains reveals gluten-induced immune signatures in celiac disease ' , Scientific Reports , vol. 7 , 17977 . https://doi.org/10.1038/s41598-017-18137-9 en
dc.identifier.issn 2045-2322
dc.identifier.other PURE: 96903501
dc.identifier.other PURE UUID: 8ca53bad-529f-4c2f-87fb-ae1f2852adf6
dc.identifier.other WOS: 000418562100017
dc.identifier.other Scopus: 85042362293
dc.identifier.other ORCID: /0000-0001-9195-9003/work/46650198
dc.identifier.uri http://hdl.handle.net/10138/231267
dc.description.abstract Celiac disease (CD) patients mount an abnormal immune response to gluten. T-cell receptor (TCR) repertoires directed to some immunodominant gluten peptides have previously been described, but the global immune response to in vivo gluten exposure in CD has not been systematically investigated yet. Here, we characterized signatures associated with gluten directed immune activity and identified gluten-induced T-cell clonotypes from total blood and gut TCR repertoires in an unbiased manner using immunosequencing. CD patient total TCR repertoires showed increased overlap and substantially altered TRBV-gene usage in both blood and gut samples, and increased diversity in the gut during gluten exposure. Using differential abundance analysis, we identified gluten-induced clonotypes in each patient that were composed of a large private and an important public component. Hierarchical clustering of public clonotypes associated with dietary gluten exposure identified subsets of highly similar clonotypes, the most proliferative of which showing significant enrichment for the motif ASS[LF] R[SW][TD][DT][TE][QA][YF] in PBMC repertoires. These results show that CD-associated clonotypes can be identified and that common gluten associated immune response features can be characterized in vivo from total repertoires, with potential use in disease stratification and monitoring. en
dc.format.extent 12
dc.language.iso eng
dc.relation.ispartof Scientific Reports
dc.rights en
dc.subject USAGE en
dc.subject REPERTOIRES en
dc.subject CHALLENGE en
dc.subject DIVERSITY en
dc.subject PACKAGE en
dc.subject CD4(+) en
dc.subject GENES en
dc.subject 3111 Biomedicine en
dc.title Deep sequencing of blood and gut T-cell receptor beta-chains reveals gluten-induced immune signatures in celiac disease en
dc.type Article
dc.description.version Peer reviewed
dc.identifier.doi https://doi.org/10.1038/s41598-017-18137-9
dc.type.uri info:eu-repo/semantics/other
dc.type.uri info:eu-repo/semantics/publishedVersion
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