Canadian Digestive Disease Week 2025 Research Round-Up:
Key Takeaways from the Celiac Disease Sessions
By Caleigh McAulay, RD and Celiac Canada’s Health Promotion Manager.
March 2025
The Canadian Digestive Diseases Week (CDDW) conference featured several groundbreaking sessions on celiac disease, led by some of the top researchers in the field. Here’s a summary of the key insights from the conference, covering recent advancements in immunogenetics, diagnostic tools, and monitoring approaches for celiac disease.
Here are some key takeaways that impact the celiac community and our path forward:
1. Immunogenetics of Celiac Disease
Presented by Alberto Caminero, PhD – Farncombe Family Digestive Health Research Institute
Caminero, a past J.A. Campbell grant recipient, highlighted the complex interplay between genetics, environmental factors, and immune response in celiac disease (CD):
Environmental Driver: Gluten is the primary environmental trigger of CD.
Genetic Susceptibility: HLA-DQ2 and HLA-DQ8 are the major genetic risk factors.
Gluten and the Immune System:
Gluten is rich in proline, making it difficult to digest and resistant to human digestive enzymes
The immunodominant 33-mer peptide is highly reactive in CD
Tissue transglutaminase 2 (TG2) modifies gluten, enhancing its ability to bind antigen-presenting cells
Gluten-specific CD4+ T-cells drive the adaptive immune response
Innate Immunity and Tissue Damage:
Increased intraepithelial lymphocytes (IELs) are a hallmark of CD
Overexpression of IL-15 in the epithelium contributes to immune activation
These findings reinforce the idea that both genetic predisposition and environmental factors play crucial roles in disease onset.
2. The Role of Genetics in Clinical Practice
Presented by Dr. Sonia S. Kupfer, The University of Chicago, Section of Gastroenterology, Professor of Medicine.
Kupfer delivered an engaging talk on how genetic testing is being used in clinical practice for diagnosing and assessing CD risk.
Genotype Testing:
HLA-DQ2 and HLA-DQ8 are the primary genetic markers for celiac disease.
Even in identical twins, the concordance rate for CD is only 80%, indicating that other environmental or epigenetic factors contribute to disease development.
HLA Risk Gradients:
Highest Risk: DQ2 homozygotes (2 copies of DQ2).
Moderate Risk: 5 trans.
Low Risk: DQ7, which is under investigation as a potential risk factor.
Clinical Implications:
Genetic testing is valuable for ruling out CD (high negative predictive value).
It is important to ensure both alpha and beta chains of HLA genes are tested for accurate risk assessment.
These insights help refine genetic screening tools, making them more effective for risk assessment and disease exclusion.
3. Advances in Celiac Disease Diagnosis and Monitoring
Presented by Dr. Jason Tye-Din, Gastroenterologist who heads the Coeliac Research Group at the Walter and Eliza Hall Institute.
Current diagnostic methods for celiac disease rely on small intestinal biopsies, which are invasive and not always reliable. Tye-Din discussed emerging immune-based diagnostic approaches that could transform how CD is diagnosed and monitored.
Challenges of Biopsy-Based Diagnosis:
Villous atrophy can be caused by other factors (infections, medications), making diagnosis difficult.
ESPGHAN has adopted a no-biopsy approach for children with very high anti-TTG levels (>10x normal), which could be expanded.
T-Cell Activation and Cytokine Responses:
Gluten-specific T-cell tests could improve diagnostic accuracy.
Cytokine responses, particularly IL-2, rise significantly in CD patients after gluten ingestion, making it a highly sensitive and specific biomarker.
IL-2 levels could predict symptom severity and individual gluten tolerance.
Potential future use of IL-2 testing for non-invasive monitoring and drug development.
This shift toward immune-based diagnostics could eventually replace invasive biopsy-based methods, offering a more patient-friendly approach.
4. Gluten Immunogenic Peptides (GIP) for Monitoring Gluten Exposure
Presented by Jocelyn Silvester
Silvester discussed the challenges of monitoring gluten exposure in celiac disease patients and explored the potential of gluten immunogenic peptides (GIP) as an objective tool.
Limitations of Traditional Monitoring Methods:
TTG-IgA is not a reliable follow-up marker (sensitivity ~50%).
Symptoms alone are unreliable indicators of gluten exposure.
GIP Testing:
Detects gluten fragments in urine or stool.
Stool GIP tests are more accurate than urine tests.
In a study, one-third of patients on a gluten-free diet (GFD) had positive GIP tests, confirming that unintentional gluten exposure is common.
Implications for Patient Counseling:
Complete gluten avoidance is nearly impossible.
GIP testing can provide real-time feedback on gluten exposure, offering a more personalized approach to diet management.
This tool could empower patients by providing more accurate insights into their gluten intake and help clinicians refine dietary counseling strategies.
5. Case Studies and Clinical Considerations
Presented by:
Don Duerksen, Gastroenterologist, St. Boniface Hospital, and Associate Professor, University of Manitoba
Elena Verdu, Principal Investigator, Professor, Division of Gastroenterology, and Director, Farncombe Family Digestive Health Research Institute
The conference concluded with insightful case discussions emphasizing the complexity of celiac disease diagnosis and management.
Case Study 1:
Patient: TTG and EMA positive, but normal biopsy and negative HLA-DQ2/DQ8.
Key Takeaway: Though rare, celiac disease can sometimes occur without classic genetic markers. Further gene testing (DQ7, DQ2.2) and clinical follow-up are necessary.
Case Study 2:
Patient: Biopsy showed Marsh 3 changes but had low TTG levels and felt asymptomatic.
Key Takeaway: Pathology interpretation is crucial—misorientation of biopsy samples can lead to misdiagnosis. Clinical and histological improvements over time are a positive indicator.
Final Thoughts
The research presented at CDDW underscores the evolving landscape of celiac disease diagnostics, monitoring, and genetic risk assessment. The development of non-invasive tests, such as IL-2 cytokine response and GIP testing, could revolutionize how we diagnose and manage CD. Additionally, the expanding understanding of non-HLA genetic factors and their clinical applications could refine risk assessment strategies.
With these advancements, we move closer to a more precise, personalized approach to celiac disease care— one that minimizes invasive procedures and empowers patients with better tools to manage their health.
What’s Next?
Stay tuned for further research updates and practical insights as these new diagnostic and monitoring tools become more widely available.