Published August 7, 2019
| Version v1
Journal article
Open
Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease
Creators
- 1. Massachusetts General Hospital
- 2. The Walter and Eliza Hall Institute
- 3. University of Oslo
- 4. University of Chicago
- 5. ImmusanT Inc.
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.
Data availability
All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.Files
sciadv.aaw7756.pdf
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Supplementary materials md5:7a42abb991b1e982be5ce295f4176145 |
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Article md5:5151125435fabab4b96c5eac0b6b7e16 |
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Additional details
Identifiers
- DOI
- 10.1126/sciadv.aaw7756
- Other
- oai:uchicago.tind.io:10968
Funding
- National Institutes of Health
- RO1DK67180
- National Institutes of Health
- R01DK098435
- University of Chicago
- Digestive Diseases Research Core Center
- The Research Council
- 179573/V40
- Research Council of Norway
- 179573/V40
- Stiftelsen KG Jebsen
- SKGH-MED-017
- The South-Eastern Norway Regional Health Authority
- 2013046
- Massachusetts General Hospital
- The Paul and Kathy Severino Research Fund
- University of Melbourne
- The Mathison Centenary Fellowship