Celiac Disease, Refractory Celiac Disease, Small Bowel Disease
Conditions
Keywords
celiac disease, duodenal biopsy, histology, digital morphometry, artificial intelligence, RNA sequencing, transcriptomics, organoids, small bowel, villous atrophy, molecular profiling, machine learning
Brief summary
This prospective cohort study aims to establish reliable histological reference values for normal small-bowel mucosa, improve histological diagnostic quality in celiac disease, and develop an advanced molecular profile for disease diagnosis and treatment response evaluation. The study will collect duodenal biopsies from three groups: healthy controls undergoing clinically indicated gastroscopy, patients referred for primary celiac disease diagnostics, and patients with small-bowel mucosal injury unresponsive to a gluten-free diet. Patients will undergo routine clinical assessment via standard pathology review of diagnostic biopsies. Biopsies will be analyzed using digital morphometry, AI-based image analysis, RNA sequencing (transcriptomics), and intestinal organoid cultures.
Detailed description
Celiac disease is a chronic autoimmune condition affecting approximately 2.4% of the Finnish population. Despite advances in diagnostics, histological assessment of duodenal biopsies remains the gold standard for diagnosis in most cases. However, histological evaluation is subject to inter-observer variability, with a 10% diagnostic error rate reported in international multicenter studies. This study will: 1. Establish reliable digital morphometric reference values (villus-to-crypt ratio) for normal small-bowel mucosa using digitized biopsy slides and AI/machine-learning-based analysis tools; 2. Investigate molecular pathways underlying celiac disease progression and treatment response through RNA sequencing (RNA-Seq transcriptomics) of biopsies from celiac disease patients and healthy controls, with a reference comparison to a drug-trial dataset; 3. Model disease progression and refractory small-bowel injury using intestinal organoid cultures derived from biopsies of celiac patients, refractory patients, and healthy controls. Research biopsy samples will be processed at the Tampere University Celiac Disease Research Center under pseudonymization. Statistical analyses will be done in collaboration with the study statistician. All data will be stored for 15 years following study completion.
Interventions
None listed
Sponsors
Tampere University Hospital
Tampere University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Age ≥ 18 years * Clinically indicated upper gastrointestinal endoscopy (gastroscopy) * Written informed consent obtained prior to procedure * For Group 1 (Healthy Controls): Negative celiac disease antibodies (anti-transglutaminase and/or anti-endomysium); no suspected celiac * For Group 2 (Celiac Diagnostics): Referred for primary celiac disease diagnostics requiring duodenal biopsy * For Group 3 (Refractory Injury): Confirmed small-bowel mucosal injury not responsive to a gluten-free diet
Exclusion criteria
* For Group 1 (Healthy Controls): Other small-bowel diseases causing mucosal injury, including Crohn's disease and small-bowel ulcers * Inability to provide written informed consent * Refusal to participate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Villus-to-crypt ratio | Research biopsy obtained at time of endoscopy; digital morphometry performed through study completion (up to December 31, 2025) | Villus-to-crypt ratio in normal duodenal mucosa established by digital morphometry |
| Transcriptomic | Research biopsy obtained at time of endoscopy; RNA-Seq analysis performed through study completion (up to December 31, 2025) | Transcriptomic (RNA-Seq) profile of duodenal mucosa in celiac disease patients and healthy controls |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AI/machine-learning-based image analysis | Throughout study period up to December 31, 2035 | Development and validation of an AI/machine-learning-based image analysis tool for grading small-bowel mucosal damage |
| Organoid culture models of celiac | Throughout study period up to December 31, 2035 | Organoid culture models of celiac and refractory small-bowel epithelial inflammatory responses at the cellular and molecular level |
| Comparison of transcriptomic profiles | Throughout study period up to December 31, 2035 | Comparison of transcriptomic profiles between this cohort and the reference drug-trial dataset |
Countries
Finland
Contacts
CONTACTJuha Taavela
Outcome results
None listed