Tissue Destruction and Healing in Celiac Disease

Celiac disease is an autoimmune enteropathy characterized by chronic inflammation of the small intestinal mucosa triggered by gluten uptake that occurs in genetically susceptible individuals carrying the specific class II human leucocyte antigens (HLA) DQ2 and DQ8 alleles. There is a spectrum in intestinal tissue damage associated with celiac disease. Some individuals develop inflammatory immunity in the absence of tissue damage, while others experience tissue damage ranging from partial to total villous atrophy. Persistent mucosal damage is associated with several severe complications, including lymphoproliferative malignancy and bone diseases. In addition, individuals with active celiac disease display a wide range of clinical symptoms, including metabolic defects that are not correlated to the degree of villous atrophy. Although much progress has been made in understanding celiac disease, major gaps remain in understanding biological mechanisms underlying inter-individual differences in clinical presentations and capacity to heal while maintaining a gluten-free diet.

Inclusion criteria

Gluten challenge group:

• Age 18 to 75 years old
• Diagnosis of Celiac disease for at least 12 months by intestinal biopsy
• Follow a strict gluten-free diet for at least the 12 consecutive months

Gluten de-challenge group:

• Age 18 to 75 years old
• Showing typical celiac disease symptoms
• Not on a gluten-free diet

Control group:

• Age 18 to 75 years old
• Females who are not pregnant

Exclusion criteria

Gluten challenge group:

• Diagnosis of any severe complication of celiac disease
• Diagnosis of other chronic, active GI disease
• Selective IgA deficiency
• Severe reaction to gluten exposure
• Any clinically significant diseases
• History of significant substance or alcohol abuse
• Pregnant or lactating
• Diagnosis of blood clotting disorders

Gluten de-challenge group:

• History of chronic inflammatory gastrointestinal disease
• Gastrointestinal illness within the 4-week period prior to screening
• History of lymphoproliferative disease
• Uncontrolled blood clotting disorders
• Any clinically significant diseases
• History of significant substance or alcohol abuse

Control group:

• Taking antibiotics, proton pump inhibitors, aspirin, or non-steroidal anti-inflammatory drugs
• Known intestinal inflammation
• Prior gastrointestinal surgery
• Taking of antiplatelet agents or anticoagulants
• Family history of celiac disease