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

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.

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