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Celiac.com 08/19/2019 - Most gluten-free celiac patients will experience gastrointestinal symptoms within hours of gluten exposure. A number of studies have shown a connection between cytokines and adverse gluten-reactions. A team of researchers recently set out to examine systemic cytokine profiles and their connection to acute symptoms in celiac disease patients after reactivation of gluten immunity. To do this, the team carried out a series of multiplex cytokine measurements in celiac disease patients after a gluten challenge, both orally, and by injection. The research team included 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, and Robert P. Anderson. Patients receiving gluten by injection showed at least 15 elevated plasma cytokines, with IL-2, IL-8, and IL-10 being most common, with changes 272-fold, 11-fold, and 1.2-fold, respectively. IL-2 and IL-8 were the only cytokines elevated at 2 hours, prior to symptom onset. After gluten ingestion, IL-2 was the earliest and most prominent cytokine, with a 15-fold change after 4 hours. Supported by studies of patient-derived gluten-specific T cell clones and primary lymphocytes, the team's observations indicate that celiac-associated gastrointestinal symptoms are likely caused by rapid reactivation of gluten-specific CD4+ T cells by gluten. This research may lead to new ways to diagnose and treat those with celiac disease. Stay tuned for more on this and related stories. Read more at: Science Advances 07 Aug 2019:Vol. 5, no. 8. DOI: 10.1126/sciadv.aaw7756 The researchers in this study are variously affiliated with the Division of Gastroenterology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA, USA; Immunology Division, The Walter and Eliza Hall Institute, Parkville, VIC, Australia; the Department of Medical Biology, University of Melbourne, Parkville, VIC, Australia; the Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, VIC, Australia; the Centre for Food and Allergy Research, Murdoch Children’s Research Institute, Parkville, VIC, Australia; the Department of Immunology and KG Jebsen Coeliac Disease Research Centre, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway; the Department of Pediatrics, Department of Medicine, University of Chicago, Chicago, IL, USA; ImmusanT Inc., Cambridge, MA, USA; and the Department of Gastroenterology and KG Jebsen Coeliac Disease Research Centre, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway.
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Celiac.com 11/11/2009 - Although doctors view celiac disease mainly as a gastrointestinal disease, it is now known to have widespread systemic manifestations. A team of researchers recently set out to define the nature and role of systemic cytokine levels in the pathophysiology of celiac disease. The research team was made up of John Sanil Manavalan, Lincoln Hernandez, Jayesh Girish Shah, John Konikkara, Afzal Jamal Naiyer, Anne Roland Lee, Edward Ciaccio, Maria Theresa Minaya, Peter H.R. Green, and Govind Bhagat of the Departments of Medicine and Pathology at Columbia University's College of Physicians and Surgeons. The team conducted multiplex cytokine assays on four different groups of adult patients: patients with active celiac disease; patients on a gluten-free diet with positive TTG IgA antibodies, patients on a gluten-free diet with negative antibodies; and those with refractory celiac disease. They then compared the results against the values in healthy adult controls. Patients with active celiac disease and those on gluten-free diet with positive antibodies showed substantially higher levels of pro-inflammatory cytokines, such as interferon-, interleukin (IL)–1, tumor necrosis factor–, IL-6 and IL-8, and also Th-2 cytokines such as IL-4 and IL-10, compared with normal controls and patients on a gluten-free diet without antibodies. One interesting finding was that patients following a gluten-free diet for under 1 year showed substantially higher levels of both pro-inflammatory cytokines and Th2 cytokines compared with the patients on gluten-free diet for more than 1 year. Moreover, the team noted a statistically significant association between levels of TTG IgA titers and serum levels of Th-2 cytokines IL-4 (p 0.001), IL-10 (p 0.001) and inflammatory cytokines such as IL-1 (p 0.001), IL-1 (p 0.005), and IL-8 (p 0.05). Journal of Human Immunology, 2009. j.humimm.2009.09.351