Celiac disease: from pathogenesis to novel therapies

Area of Science:

• Immunology
• Gastroenterology
• Genetics

Background:

• Celiac disease is a well-understood HLA-linked disorder.
• It shares features with inflammatory bowel disease but has a defined trigger (gluten) and requires specific HLA types (HLA-DQ2/HLA-DQ8).
• Key features include autoantibodies to tissue transglutaminase (TG2), which modifies gluten peptides, enhancing T-cell activation and causing inflammation.

Purpose of the Study:

• To review the pathogenesis of celiac disease.
• To discuss emerging non-dietary therapies for celiac disease.
• To critically evaluate novel therapeutic strategies in clinical trials.

Main Methods:

• Review of current understanding of celiac disease immunopathogenesis.
• Analysis of targeted non-dietary therapies in development.
• Discussion of clinical trial data for novel celiac disease treatments.

Main Results:

• Gluten triggers adaptive and innate immune responses, leading to inflammation and malabsorption.
• Dietary gluten exclusion is the primary treatment but is less effective in refractory cases.
• Several novel therapies targeting gluten processing, immune activation, and gut permeability are in early-stage clinical trials.

Conclusions:

• Understanding celiac disease pathogenesis has led to innovative non-dietary therapeutic approaches.
• Experimental therapies include modified gluten, enzyme degradation, permeability reduction, TG2 inhibition, and immune modulation.
• These novel strategies offer potential alternatives or adjuncts to a gluten-free diet, particularly for refractory celiac disease.