Histomolecular Profiling in Small-Bowel Diseases

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:

• 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;
• 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;
• 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.

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