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

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http://hdl.handle.net/10138/231267

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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

Title: Deep sequencing of blood and gut T-cell receptor beta-chains reveals gluten-induced immune signatures in celiac disease
Author: Yohannes, Dawit A.; Freitag, Tobias L.; de Kauwe, Andrea; Kaukinen, Katri; Kurppa, Kalle; Wacklin, Pirjo; Mäki, Markku; Arstila, T. Petteri; Anderson, Robert P.; Greco, Dario; Saavalainen, Päivi
Contributor: University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Medicum
University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
Date: 2017-12-21
Language: eng
Number of pages: 12
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/231267
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.
Subject: USAGE
REPERTOIRES
CHALLENGE
DIVERSITY
PACKAGE
CD4(+)
GENES
3111 Biomedicine
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