Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease

Gautam Goel, Jason A. Tye-Din, Shuo Wang Qiao, Amy K. Russell, Toufic Mayassi, Cezary Ciszewski, Vikas K. Sarna, Suyue Wang, Kaela E. Goldstein, John L. Dzuris, Leslie J. Williams, Ramnik J. Xavier, Knut E.A. Lundin, Bana Jabri, Ludvig M. Sollid, Robert P. Anderson

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

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.

Original languageEnglish
Article numbereaaw7756
JournalScience advances
Volume5
Issue number8
DOIs
StatePublished - 7 Aug 2019
Externally publishedYes

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