'Rogue' immune cells may explain why some celiac patients do not recover on a gluten-free diet

Researchers at the Garvan Institute of Medical Research and UNSW Sydney have uncovered new insights into why certain individuals with celiac disease continue to experience symptoms despite strictly avoiding gluten. Their groundbreaking study, published in Science Translational Medicine, employed advanced single-cell sequencing techniques to analyze immune cells in the gut. The team discovered that some patients harbor immune cells with genetic mutations—referred to as "rogue" immune cells—that persist and promote ongoing intestinal inflammation.

Celiac disease is an autoimmune disorder where the immune system mistakenly attacks the small intestine when exposed to gluten, a protein in wheat, barley, and rye. While most patients find symptom relief by eliminating gluten, approximately 1% develop refractory celiac disease, where symptoms persist despite dietary control. Refractory celiac disease is classified into two types: Type 2, caused by abnormal immune cells that can lead to lymphoma, and Type 1, whose underlying cause has long remained elusive—until now.

Professor Chris Goodnow explained that their findings reveal a molecular signature specific to Type 1 refractory celiac disease. They identified immune cells with mutations that plant them with a growth and survival advantage, akin to those seen in lymphomas. These mutated cells are present in about 70% of the patients studied, suggesting a potential reason why some do not respond fully to a gluten-free diet.

This discovery points toward new diagnostic and therapeutic strategies. Presently, treatments involve broad immunosuppression, which can weaken the immune system without targeting the root cause. The team proposes that drugs targeting specific mutated immune cells—such as JAK inhibitors—could offer more precise interventions.

Dr. Manu Singh highlighted that advanced genomic technologies are now making it possible to detect these abnormal immune cells, which were previously undetectable. This progress could enable earlier identification of at-risk patients and personalized treatment plans, paving the way for more effective management of refractory celiac disease.

Overall, this research significantly advances our understanding of celiac disease mechanisms and opens new avenues for targeted therapies, ultimately aiming to improve outcomes for patients who do not improve with conventional gluten-free diets.

source: https://medicalxpress.com/news/2025-05-rogue-immune-cells-gluten-free.html