Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease
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2019-08-07
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Science Advances
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AMER ASSOC ADVANCEMENT SCIENCE
Melbourne Authors
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Medical Biology (W.E.H.I.)
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Journal Article
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Goel, G., Tye-Din, J. A., Qiao, S. W., Russell, A. K., Mayassi, T., Ciszewski, C., Sarna, V. K., Wang, S., Goldstein, K. E., Dzuris, J. L., Williams, L. J., Xavier, R. J., Lundin, K. E. A., Jabri, B., Sollid, L. M. & Anderson, R. P. (2019). Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease. Science Advances, 5 (8), https://doi.org/10.1126/sciadv.aaw7756.
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Abstract
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.