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  • Jefferson Adams
    Jefferson Adams

    How Refining the Gluten Challenge May Help Improve Diagnostics for Celiac Disease

    Reviewed and edited by a celiac disease expert.

    Now, a new study sheds light on new biomarkers that could help to rapidly improve the way celiac disease is diagnosed and researched. Here's what it revealed.

    How Refining the Gluten Challenge May Help Improve Diagnostics for Celiac Disease - Vision of Transformation. Image: CC BY-ND 2.0--h.koppdelaney
    Caption: Vision of Transformation. Image: CC BY-ND 2.0--h.koppdelaney

    Celiac.com 06/08/2023 - For people who suspect they have celiac disease, an accurate diagnosis is crucial for managing health and making informed dietary choices. Traditionally, the gold standard for celiac diagnosis has involved a gluten challenge, where individuals are required to consume gluten-containing foods to induce disease activity. 

    However, this approach can be burdensome and time-consuming. Now, a new study conducted at two US centers has shed light on new biomarkers that could help to rapidly improve the way celiac disease is diagnosed and researched.

    The Research Team

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    The research team included Maureen M. Leonard, Jocelyn A. Silvester, Daniel Leffler, Alessio Fasano, Ciarán P. Kelly, Suzanne K. Lewis, Jeffrey D. Goldsmith, Elliot Greenblatt, William W. Kwok, William J. McAuliffe, Kevin Galinsky, Jenifer Siegelman, I-Ting Chow, John A. Wagner, Anna Sapone, and Glennda Smithson.

    They are variously affiliated with the Center for Celiac Research and Treatment, Massachusetts General Hospital, Boston, Massachusetts; the Celiac Disease Research Program, Harvard Medical School, Boston, Massachusetts; the Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Boston Children’s Hospital, Boston, Massachusetts; the Celiac Center, Beth Israel Deaconess Medical Center, Boston, Massachusetts; Takeda Pharmaceuticals Inc. Co., Cambridge, Massachusetts; the Department of Medicine, Columbia University Medical Center, New York, New York; the Department of Pathology, Boston Children’s Hospital, Boston, Massachusetts; Invicro, A Konica Minolta Company, Boston, Massachusetts; and the Benaroya Research Institute at Virginia Mason, Seattle, Washington.

    A Randomized Double-blind Trial

    In a randomized, double-blind trial, the team enrolled 14 adults with biopsy-proven celiac disease. The participants were divided into two groups and assigned to consume either 3 grams or 10 grams of gluten per day for a period of 14 days. 

    The primary objective was to assess the changes in villous height: crypt depth (Vh:celiac disease), a key histological marker of celiac disease activity. However, the study also aimed to explore other biomarkers that could potentially supplement or even replace histology as a diagnostic tool.

    The results of the study were largely encouraging. All of the biomarkers assessed showed changes in response to gluten challenge, demonstrating their potential for evaluating disease activity. However, the time to reach maximal change, the magnitude of change, and the gluten dose-response relationship varied across different biomarkers. 

    Notably, Vh:celiac disease, a measure of the structural integrity of the small intestine, VCE enteropathy score as assessed by video capsule endoscopy, enzyme-linked immune absorbent spot (ELISpot), gut-homing CD8 T cells, intraepithelial leukocytes, and gluten-specific CD4 T cells, all demonstrated significant changes only at the higher gluten dose of 10 grams. 

    However, symptoms reported by the participants, and plasma interleukin-2 (IL-2) levels, increased significantly or near significantly at both gluten doses. Interestingly, IL-2 appeared to be the earliest and most sensitive marker of acute gluten exposure.

    Conclusions

    These findings can help to improve celiac disease diagnostics, by identifying modern biomarkers that are sensitive and responsive to gluten exposure, this study offers the possibility of less invasive and shorter-duration gluten challenges. This would not only ease the burden on individuals undergoing diagnostic testing but also streamline celiac disease research, enabling more efficient and precise investigations.

    The potential benefits of these novel biomarkers extend beyond diagnostics. They could also play a crucial role in monitoring disease activity, assessing treatment responses, and even exploring the effects of gluten on individuals who are at risk of developing celiac disease.

    While this study represents a significant step forward, further research is needed to validate and refine the biomarkers. Future studies may investigate their utility in larger populations and explore their correlation with long-term clinical outcomes.

    This study shows the potential for modern biomarkers to improve celiac disease diagnostics. By providing a preliminary framework for the rational design of gluten challenge protocols, this work brings us one step closer to more efficient and patient-friendly diagnostic approaches for celiac disease.

    Stay tuned for more on this and related stories.

    Read more in Gastroenterology


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    knitty kitty

    According to this recent research, updates to the gluten challenge are being implemented.

    Recommended intake of gluten should be increased to 10 grams of gluten per day for at least two weeks. Or longer.

    While three grams of gluten will begin the immune response, ten grams of gluten is needed to get antibody levels up to where they can be measured in antibody tests and changes can be seen in the small intestine.  

    Keep in mind that there are different amounts of gluten in different kinds of bread and gluten containing foods.  Pizza crust and breads that are thick and chewy contain more gluten than things like cake and cookies.  

    References:

    https://www.beyondceliac.org/celiac-disease/the-gluten-challenge/

    And...

    Evaluating Responses to Gluten Challenge: A Randomized, Double-Blind, 2-Dose Gluten Challenge Trial

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878429/?report=reader

     "In our study, limited changes in Vh:celiac disease (villi height vs crypt depth - aka damage to the small intestine)  following 14-day challenge with 3 g of gluten were observed, in accordance with Sarna et al.  While the 3 g dose was sufficient to initiate an immune response, as detected by several biomarkers such as IL-2, the 10 g dose was required for enteropathy within the study time frame. Based on our data, we would suggest that gluten challenge should be conducted over longer durations and/or using doses of gluten of ≥ 3 g/day to ensure sufficient histological change can be induced."
    Keep us posted on your progress!

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    Ginger38
    1 hour ago, knitty kitty said:

    According to this recent research, updates to the gluten challenge are being implemented.

    Recommended intake of gluten should be increased to 10 grams of gluten per day for at least two weeks. Or longer.

    While three grams of gluten will begin the immune response, ten grams of gluten is needed to get antibody levels up to where they can be measured in antibody tests and changes can be seen in the small intestine.  

    Keep in mind that there are different amounts of gluten in different kinds of bread and gluten containing foods.  Pizza crust and breads that are thick and chewy contain more gluten than things like cake and cookies.  

    References:

    https://www.beyondceliac.org/celiac-disease/the-gluten-challenge/

    And...

    Evaluating Responses to Gluten Challenge: A Randomized, Double-Blind, 2-Dose Gluten Challenge Trial

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878429/?report=reader

     "In our study, limited changes in Vh:celiac disease (villi height vs crypt depth - aka damage to the small intestine)  following 14-day challenge with 3 g of gluten were observed, in accordance with Sarna et al.  While the 3 g dose was sufficient to initiate an immune response, as detected by several biomarkers such as IL-2, the 10 g dose was required for enteropathy within the study time frame. Based on our data, we would suggest that gluten challenge should be conducted over longer durations and/or using doses of gluten of ≥ 3 g/day to ensure sufficient histological change can be induced."
    Keep us posted on your progress!

    Is there a way to know how much gluten is in something specifically? 

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    knitty kitty

    Not that I know of, unfortunately.  

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    Ginger38
    10 hours ago, knitty kitty said:

    Not that I know of, unfortunately.  

    So it only takes 3 grams to start an immune response- but no idea what 3 grams would be eating?

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    knitty kitty

    On average, a slice of bread contains about 2 grams of gluten.  Three grams of gluten is enough to make you feel unwell, but TEN grams of gluten gets the anti gluten antibodies into the bloodstream at a high enough level where they can be measured for blood tests for Celiac Disease and to produce noticeable damage in the small intestine.

    Different breeds of wheat contain different amounts of gluten depending on breed and growing conditions.  Manufacturers blend different wheats together to get the amount of gluten required to make their products.  

    The addition of vital wheat gluten to different types of bread also affects the total amount of gluten in a product.  

    Can an Increase in Celiac Disease Be Attributed to an Increase in the Gluten Content of Wheat as a Consequence of Wheat Breeding?

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573730/

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    Ginger38
    On 4/12/2024 at 10:46 AM, knitty kitty said:

    On average, a slice of bread contains about 2 grams of gluten.  Three grams of gluten is enough to make you feel unwell, but TEN grams of gluten gets the anti gluten antibodies into the bloodstream at a high enough level where they can be measured for blood tests for Celiac Disease and to produce noticeable damage in the small intestine.

    Different breeds of wheat contain different amounts of gluten depending on breed and growing conditions.  Manufacturers blend different wheats together to get the amount of gluten required to make their products.  

    The addition of vital wheat gluten to different types of bread also affects the total amount of gluten in a product.  

    Can an Increase in Celiac Disease Be Attributed to an Increase in the Gluten Content of Wheat as a Consequence of Wheat Breeding?

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573730/

    Thank you for this great information! I appreciate it. Does gluten build up on a day to day basis? Like if a person consumes 1-2 grams of gluten today and then another 1-2 tomorrow, does that become more like 4 gm of gluten in your body? And so on? 

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    knitty kitty

    No, you can't add it up that way.  

    Gluten stimulates anti gluten antibodies to be made.  Those antibodies are what become cumulative.  Ten grams a day for several weeks, gets those antibodies produced in the small intestine to a level where those antibodies get into the bloodstream in a high enough level that they are measurable in the bloodstream.  

    Gluten itself mostly stays in the digestive tract and is removed with bowel movements.  However, if one has leaky gut syndrome, gluten can travel to other places.  For example, joint inflammation and pain can be caused by gluten congregating in joints.  That's why it's important to heal the digestive tract so it doesn't leak.  The AIP diet and Benfotiamine are beneficial in this respect.

     

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    Ginger38
    6 minutes ago, knitty kitty said:

    No, you can't add it up that way.  

    Gluten stimulates anti gluten antibodies to be made.  Those antibodies are what become cumulative.  Ten grams a day for several weeks, gets those antibodies produced in the small intestine to a level where those antibodies get into the bloodstream in a high enough level that they are measurable in the bloodstream.  

    Gluten itself mostly stays in the digestive tract and is removed with bowel movements.  However, if one has leaky gut syndrome, gluten can travel to other places.  For example, joint inflammation and pain can be caused by gluten congregating in joints.  That's why it's important to heal the digestive tract so it doesn't leak.  The AIP diet and Benfotiamine are beneficial in this respect.

     

    And the antibodies are what cause the damage to the intestines correct? 

    I don’t think I could back on gluten to do the challenge and have the biopsy. I can’t imagine eating that much gluten every day for weeks.

    So if gluten doesn’t build up and is excreted out, I guess I don’t understand why sometimes gluten causes huge reactions and makes me really sick and other times it’s not near as bad. 

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    knitty kitty

    Yes, the antibodies cause damage to the intestines, and the brain, and every other organ and tissues in the body.  

    Anti-transglutaminase antibodies (anti tTg IgA on blood tests) are antibodies that attack transglutaminase, a building component in the cell membranes of every cell in the body.  

    The gluten may pass, but the antibodies are what can stay circulating for months.  

    Some gluten containing products can contain more gluten that stimulates higher antibody production than other products.  Chewy breads with those big bubbles have more gluten than a cookie that's crumbly and not chewy like pizza dough.  Vital wheat gluten added to a product can provoke a more extreme antibody response than a product without.  

    With the higher doses of gluten in the updated challenge guidelines, you don't have to stay on the gluten challenge for months.  Sufficient changes for antibodies were seen in TWO Weeks.  

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    Ginger38
    13 hours ago, knitty kitty said:

    Yes, the antibodies cause damage to the intestines, and the brain, and every other organ and tissues in the body.  

    Anti-transglutaminase antibodies (anti tTg IgA on blood tests) are antibodies that attack transglutaminase, a building component in the cell membranes of every cell in the body.  

    The gluten may pass, but the antibodies are what can stay circulating for months.  

    Some gluten containing products can contain more gluten that stimulates higher antibody production than other products.  Chewy breads with those big bubbles have more gluten than a cookie that's crumbly and not chewy like pizza dough.  Vital wheat gluten added to a product can provoke a more extreme antibody response than a product without.  

    With the higher doses of gluten in the updated challenge guidelines, you don't have to stay on the gluten challenge for months.  Sufficient changes for antibodies were seen in TWO Weeks.  

    Thank you this is very helpful! 2 weeks is not near as long, but if it’s higher gluten intake - I feel like it’s sort of going to be the same as small amounts over a longer period of time. I just can’t stand the thought of being sick all the time. Gluten can really cause havoc all throughout my body and even land me in the ER if I have enough to trigger palpitations and tachycardia 

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    knitty kitty

    @Ginger38

    Have you had a DNA test for Celiac genes?  You don't have to eat gluten with a DNA test.  

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    Ginger38
    8 minutes ago, knitty kitty said:

    @Ginger38

    Have you had a DNA test for Celiac genes?  You don't have to eat gluten with a DNA test.  

    For what genes specifically? And if it’s negative what does that mean? 

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    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. His articles, essays, poems, stories and book reviews have appeared in numerous magazines, journals, and websites, including North American Project, Antioch Review, Caliban, Mississippi Review, Slate, and more. He is the author of more than 2,500 articles on celiac disease. His university coursework includes studies in science, scientific methodology, biology, anatomy, physiology, medicine, logic, and advanced research. He previously devised health and medical content for Colgate, Dove, Pfizer, Sharecare, Walgreens, and more. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of numerous books, including "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.

    >VIEW ALL ARTICLES BY JEFFERSON ADAMS

     


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