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Merck
  • Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease.

Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease.

Science advances (2019-08-29)
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
要旨

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.