Research Highlights from Digestive Disease Week 2024

Jocelyn Silvester, Boston Children’s Hospital / Harvard Medical School 

Gluten challenges can play an important role in accurate diagnosis of celiac disease (CeD). Dr. Jocelyn Silvester outlined the best practices for gluten challenges in diagnosis of CeD. Consumption of 3-6 grams of gluten per day for 6-12 weeks is the standard recommendation for gluten challenges to induce the necessary histological response for diagnostic clarity. Studies show that amount of gluten in food varies, so working with a healthcare team to determine the appropriate challenge food(s) is necessary.  

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Olivia Moscatelli, The Walter and Eliza Hall Institute / University of Melbourne 

In the future, an interlukin-2 (IL-2) blood test may eliminate the need for a gluten challenge to assess gluten-specific damage. In this study, the IL-2 blood test was able to detect CeD even in patients adhering to a gluten-free diet with negative serology. This research, presented by Olivia Moscatelli, highlights a potential non-invasive diagnostic pathway for CeD.

Denis Chang, Boston Children’s Hospital 

Follow-up endoscopy for intestinal healing in CeD is not always performed despite clinical guidelines. In this multicenter study of newly diagnosed pediatric patients, more than 50% experienced intestinal healing within the first year, with some seeing healing as early as 3 months. This underscores the need for future studies aimed at better understanding the timeline and factors that affect mucosal healing on a gluten-free diet in pediatric patients.

Olivia Moscatelli, The Walter and Eliza Hall Institute / University of Melbourne 

CeD is driven by gluten-specific CD4+ T cells. Conventional methods to detect these cells involves a gluten challenge followed by an interferon-γ ELISpot (IFN- γ ELISpot), which are sensitive but complex. In this study, researchers assessed a new approach using IL-2 release in an in vitro whole blood assay and compared to IFN- γ ELISpot. The IL-d assay showed higher sensitivity than IFN- γ ELISpot in detecting gluten-specific T cells before and after a gluten challenge.

Maria Camila Cardenas Fernandez, Mayo Clinic 

In this multicenter study, Dr. Maria Camila Cardenas Fernandez and her team examined whether using a single blood test (positive tTG-IgA) is enough to diagnose celiac disease (CeD) in children. They found significant differences in positive blood samples among thousands of patients (n=2,397), suggesting that the current thresholds may not be adequate for diagnosis in some patients. Unlike European Pediatric Gastroenterology Societies, North American Pediatric Gastroenterology Societies still require an endoscopy to confirm CeD diagnosis in those who have a positive blood test. 

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Mohammad Karam Chaaban, Mayo Clinic Minnesota 

Follow up care every 12-24 months in CeD is critical for preventing long-term complications associated with CeD and the gluten-free diet. In this study, researchers found over half of pediatric CeD patients had suboptimal follow up based on serology, and one-third of patients did not have any documentation of CeD within the last 2 years of clinical follow up. However, use of an AI natural language processing algorithm effectively identified children with CeD to optimize their follow up care. 

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Rachel Leong, McMaster University 

This study explored the impact of food insecurity on adherence to a gluten-free diet among individuals with CeD. The findings suggest that food insecurity is linked to poorer adherence to the gluten-free diet, increased GI symptoms, reduced quality of life, and increased anxiety and depression. This highlights the need for support and resources to help individuals with CeD access safe and nutritious food. 

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Celia Jarweh, Universite de Montreal 

Generic quality of life (QoL) assessments are often used in research, but many do not reflect the challenges experienced by pediatric patients with CeD. In this prospective cross-sectional study (n=112), researchers from Canada demonstrated how CeD-specific QoL questionnaires offer a more precise assessment of QoL issues in pediatric CeD patients. In this cohort, current age, age at diagnosis, recent gluten consumption, and recent clinical symptoms had a significant impact on QoL in CeD patients, while gender, comorbidities, and familial revenues did not. 

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The findings in this study suggest that there is a notable overlap between CeD and eosinophilic esophagitis (EoE), and that patients with co-occurring CeD and EoE have lower risk for swallowing difficulty and food impaction than those with EoE alone. The researchers suggest that a possible explanation could be related to the CeD cohort already being on a wheat-free diet, which is a key component of EoE treatment in many patients.   

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Micaela Atkins, Massachusetts General Hospital 

In this study, clinically significant symptoms of Avoidant / Restrictive Food Intake Disorder (ARFID) were present in 18% of CeD patients at initial consultation, and in 20% of patients at one-year follow up. This highlights the importance of screening for ARFID in CeD patients, particularly those with weight or growth concerns. 

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Saad Saadat, Indiana University School of Medicine 

This study compared outcomes of a dietitian-led gluten-free diet compared to self-taught individuals. The researchers found improved outcomes for individuals working with a dietitian, particularly for individuals with infertility, type 1 diabetes, short stature, and MASLD. These findings underscore the importance of working with a dietitian to manage CeD and its associated complications.   

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Giovanni Marasco, Universita di Bologna 

Digestive symptoms frequently persist in CeD patients following a strict gluten-free diet. In this study, researchers found higher rates of irritable bowel syndrome (IBS) and functional dyspepsia (FD) in CeD patients compared to that of the general population, and that these diagnoses were associated with higher levels of anxiety and longer follow up time.  

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Franziska Buriánek, Immunic Therapeutics 

Dr. Franziska Buriánek presented on IMU-856, which is a novel drug targeting the protein Sirtuin 6. Sirtuin 6 is involved in intestinal barrier function and regeneration of the intestinal epithelium. In this study, IMU-856 was safe, well-tolerated, and improved intestinal barrier function in patients with CeD undergoing a gluten challenge.

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Michael Schumann, Charité – Universitätsmedizin Berlin

This study is the first to show that using a strong antibody to block IL-15 can reduce damage to the intestines caused by gluten in people with well-managed celiac disease. These positive findings suggest that more research should be done on CALY-002 for celiac disease. 

Eva Krzyzewska-Dudek, University of Heilinski 

TAK-101, a nanoparticle containing gliadin, was studied for its ability to create immune tolerance in mice with CeD. The study showed that TAK-101 could maintain its effects for at least 6 months in mice, and it seemed to affect immune cells called B cells. This suggests that TAK-101 could be a potential treatment for CeD by regulating the immune response to gluten.

Kristie Grebe, Anokion 

In the ACeD-it study, KAN-101, an investigational therapy for CeD, was found to be safe and well-tolerated at higher dose levels (1.2 or 3.0 mg/kg) in adult patients. The therapy aims to reduce gluten-specific immune responses and modulate IL-2, a biomarker associated with symptomatic reactions to gluten. These results support further investigation of KAN-101 in Phase 2 trials to evaluate its efficacy in CeD patients. Anokion is actively enrolling patients into its Phase 2 portion of the Phase 1/b ACeD-it trial and its Phase 2a SynCeD trial in individuals with CeD. 

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