Jump to content



Celiac.com Sponsor (A1):



Celiac.com Sponsor (A1-m):


  • You've found your Celiac Tribe! Join our like-minded, private community and share your story, get encouragement and connect with others.

    💬

    • Sign In
    • Sign Up
  • Jefferson Adams
    Jefferson Adams

    Elevated Serum Interleukin-2 After Gluten Challenge Can Help Monitor Celiac Disease

    Reviewed and edited by a celiac disease expert.

    A new study shows that a gluten food challenge combined with interleukin-2 assessment could be valuable clinical tool for monitoring and diagnosing celiac disease in patients on a gluten-free diet.

    Elevated Serum Interleukin-2 After Gluten Challenge Can Help Monitor Celiac Disease - Image: CC BY 2.0--rawdonfox
    Caption: Image: CC BY 2.0--rawdonfox

    Celiac.com 12/04/2019 - There still is no easy and accurate way to monitor and diagnose celiac disease in patients who've been on a gluten-free diet for a while. Celiac disease patients on a gluten-free diet experience reactions to gluten, but researchers really don't understanding those reactions in any meaningful way. Systemic cytokine release was recently linked to reactivation of gluten immunity in celiac disease.

    A team of researchers recently set out to define the nature and time-course of symptoms and interleukin-2 changes specific for celiac disease patients. Their study shows that interleukin-2 assessment could help doctors monitor and diagnose celiac disease in patients already following a gluten-free diet.



    Celiac.com Sponsor (A12):






    Celiac.com Sponsor (A12-m):




    The research team included Jason A. Tye-Din, A. James M. Daveson, Hooi C. E, Gautam Goel, James MacDougall, Sarah Acaster, Kaela E. Goldstein, John L. Dzuris, Kristin M. Neff, Kenneth E. Truitt and Robert P. Anderson. They are variously affiliated with the Immunology Division, Department of Medical Biology, The Walter and Eliza Hall Institute, University of Melbourne, Parkville, Vic., Australia; Department of Gastroenterology, The Royal Melbourne Hospital, Parkville, Vic., Australia; University of Queensland, Brisbane, Qld, Australia; Sir Charles Gairdner Hospital, Perth, WA, Australia; ImmusanT, Inc., Cambridge, MA, USA; Prometrika, LLC, Cambridge, MA, USA; and Acaster Lloyd Consulting Ltd., London, UK.

    The team presented a gluten challenge to 25 celiac disease patients following a gluten-free diet, and to 25 healthy control subjects. Each group consumed a standardized 6 gram gluten challenge.

    The team compiled a Celiac Disease Patient-Reported Outcome survey and global digestive symptom assessment each hour for up to 6 hours after gluten challenge. They also recorded adverse events over a 48 hour period, and assessed serum interleukin-2 levels at baseline, and at 2, 4 and 6 hours.

    Healthy control subjects showed no detectable levels of serum interleukin-2, while 92% of celiac patients showed no detectable levels at baseline, but levels >0.5 pg/ml at 4 hours. Patient-reported outcome severity scores remained steady for all control subjects, while scores for celiac patients rose sharply after gluten in celiac disease patients.

    Symptoms of gluten exposure started at the 1 hour mark, and topped out after three hours. Patients with serious reactions typically suffered from nausea and vomiting, while those with milder reactions experienced headache and fatigue.

    The highest interleukin-2 levels were associated with more severe symptoms, especially nausea and vomiting. The timing and severity of gluten ingestion symptoms in people with celiac disease are strongly connected to elevated levels of serum interleukin-2.

    A gluten food challenge combined with interleukin-2 assessment could be valuable clinical tool for monitoring and diagnosing celiac disease in patients established on a gluten-free diet.

    Alimentary Pharmacology & Therapeutics



    User Feedback

    Recommended Comments

    There are no comments to display.



    Join the conversation

    You are posting as a guest. If you have an account, sign in now to post with your account.
    Note: Your post will require moderator approval before it will be visible.

    Guest
    Add a comment...

    ×   Pasted as rich text.   Restore formatting

      Only 75 emoji are allowed.

    ×   Your link has been automatically embedded.   Display as a link instead

    ×   Your previous content has been restored.   Clear editor

    ×   You cannot paste images directly. Upload or insert images from URL.


  • About Me

    Jefferson Adams

    Jefferson Adams is Celiac.com's senior writer and Digital Content Director. He earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,500 articles on celiac disease. His coursework includes studies in science, scientific methodology, biology, anatomy, medicine, logic, and advanced research. He previously served as SF Health News Examiner for Examiner.com, and devised health and medical content for Sharecare.com. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.


  • Celiac.com Sponsor (A17):
    Celiac.com Sponsor (A17):





    Celiac.com Sponsors (A17-m):




  • Related Articles

    Jefferson Adams
    Celiac.com 03/18/2011 - By blocking an inflammatory protein called interleukin-15 (IL-15), doctors may be able to treat and prevent symptoms of celiac disease in some people, according to a new study in the journal Nature.
    The data suggest that the inflammatory response to gluten in people with celiac disease may be triggered by interleukin-15 and retinoic acid, which is a derivative of vitamin A.
    The team notes that researchers previously thought that retinoic acid would lessen the inflammation in the intestine. Instead their study showed that it might actually worsen inflammation.
    According to Bana Jabri, MD, PhD, a member of the Celiac Disease Center and Comprehensive cancer Center at the University of Chicago, the team results showed that "elevated levels of IL-15 in the gut could initiate all the early stages of celiac disease in those who were genetically susceptible, and that blocking IL-15 could prevent the disease in our mouse model. It also demonstrated that in the treatment of inflammatory intestinal diseases, vitamin A and its retinoic acid metabolites are likely to do more harm than good.”
    The researchers found that by blocking IL-15 in mice that were genetically engineered to have celiac disease, they were able to reverse the symptoms, and the mice were able to eat gluten without suffering the symptoms of celiac disease.
    One reason this is good news, is that a number of medicines designed to block IL-15 are already being developed for other inflammation related diseases, such as rheumatoid arthritis.
    Source:

    Nature. 2011 Mar 10;471(7337):220-4.


    Jefferson Adams
    Celiac.com 12/07/2016 - Refractory celiac disease (RCD) is a form of celiac disease that does not respond to treatment with gluten-free diet, and often involves greater risk of complications.
    The guts of many RCD patients over-produce effector cytokines, which are supposed to amplify the tissue-destructive immune response. However, it remains unclear if the RCD-associated mucosal inflammation is sustained by defects in counter-regulatory mechanisms.
    A team of researchers recently set out to determine whether RCD-related inflammation is marked by high Smad7, an intracellular inhibitor of transforming growth factor (TGF)-β1 activity. The research team included S Sedda, V De Simone, I Marafini, G Bevivino, R Izzo, OA Paoluzi, A Colantoni, A Ortenzi, P Giuffrida, GR Corazza, A Vanoli, A Di Sabatino, F Pallone, and G Monteleone. They are variously affiliated with the Department of Systems Medicine at the University of Rome "Tor Vergata," the First Department of Internal Medicine at the Fondazione IRCCS Policlinico San Matteo of the University of Pavia, and with the Department of Molecular Medicine at San Matteo Hospital at the University of Pavia in Pavia, Italy.
    The team evaluated Smad7 in duodenal biopsy samples of patients with RCD, patients with active celiac, patients with inactive celiac disease and healthy controls by Western blotting, immunohistochemistry and real time-PCR. In the same samples, they used ELISA and immunohistochemistry to assess TGF-β1 and phosphorylated (p)-Smad2/3, respectively.
    They evaluated pro-inflammatory cytokine expression in RCD samples cultured with Smad7 sense or antisense oligonucleotide. Smad7 protein, but not RNA, expression was increased in RCD, as compared to active and inactive celiac patients and healthy controls. This increased expression was associated with defective TGF-β1 signaling, as marked by diminished p-Smad2/3 expression. TGF-β1 protein content did not differ among groups. Knockdown of Smad7 in RCD biopsy samples reduced IL-6 and TNFα expression.
    These results show that, in RCD, high Smad7 associates with defective TGF-β1 signaling, and sustains inflammatory cytokine production.
    These results suggest a novel mechanism by which amplifies mucosal cytokine response in RCD, and suggest that treatments targeting Smad7 might be helpful in RCD.
    Source:
    Immunology. 2016 Nov 14. doi: 10.1111/imm.12690.


    Jefferson Adams
    Celiac.com 11/13/2017 - ImmusanT, Inc., the company working to develop a therapeutic vaccine to protect HLADQ2.5+ patients with celiac disease against the effects of gluten, presented data that shows a way to tell the difference between celiac disease and non-celiac gluten-sensitive (NCGS) based on cytokine levels.
    Professor Knut Lundin, University of Oslo, presented the data at United European Gastroenterology (UEG) Week 2017.
    The results are important, in part because many people go on a gluten-free diet before they ever get diagnosed with celiac disease. It's hard for doctors to ask these people to start eating gluten again so that they can be properly diagnosed. But that's how it currently works. If there are no anti-gliadin antibodies in your blood, current tests are not accurate.
    These data suggest that it is possible to spot celiac disease through plasma or blood test. Along with easier, more accurate celiac diagnoses, a blood test would be a major breakthrough because "patients would only be required to consume gluten on one occasion and would still achieve accurate results," said Robert Anderson, MBChB, Ph.D., Chief Scientific Officer of ImmusanT.
    The test may also help people who do not have celiac disease, but find symptom relief on a gluten-free diet. For these people, gluten may not be the cause of their symptoms and a gluten-free diet may be totally unnecessary.
    The latest data support the company's approach to "developing a simple blood test for diagnosing celiac disease without the discomfort and inconvenience of current testing methods. This would be the first biomarker for measuring systemic T-cell immunity to gluten," said Leslie Williams, Chief Executive Officer of ImmusanT.
    As development is ongoing, further tests are expected to flesh out the details.
    Source:
    Immusant


    Jefferson Adams
    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.


  • Popular Now

×
×
  • Create New...