Coeliac disease
- Lesion
In genetically prone people, gluten from wheat, rye and barley triggers an immune attack that flattens the small-bowel lining.
What it is
Coeliac disease is an immune enteropathy requiring three ingredients: gluten, HLA-DQ2 or DQ8, and tissue transglutaminase 2 (TG2). TG2 deamidates gluten peptides, making them bind tightly to DQ2 or DQ8 on antigen-presenting cells; gluten-specific CD4 T cells then produce interferon-γ and IL-21, and IL-15 from epithelium activates cytotoxic intraepithelial CD8 T cells that kill enterocytes. The result is loss of villi and malabsorption that reverses on a gluten-free diet.
Step by step
- Gluten is digested into proline- and glutamine-rich peptides that resist further breakdown.
- TG2 deamidates glutamine to glutamic acid, giving the peptides a negative charge.
- Deamidated peptides bind HLA-DQ2 or DQ8 and activate gluten-specific CD4 T cells.
- CD4 T cells release IFN-γ and help B cells make anti-TG2 IgA.
- Epithelial IL-15 activates intraepithelial CD8 T cells, which kill enterocytes through NKG2D.
- Villi shorten while crypts proliferate to compensate: malabsorption.
Marsh–Oberhuber grades, simplified
| Grade | Intraepithelial lymphocytes | Crypts | Villi |
|---|---|---|---|
| 0 | Normal | Normal | Normal |
| 1 (infiltrative) | Increased | Normal | Normal |
| 2 (hyperplastic) | Increased | Hyperplastic | Normal |
| 3a to 3c (destructive) | Increased | Hyperplastic | Partial, subtotal or total atrophy |
Markers
- IgA anti-TG2
- IgA anti-endomysial
- HLA-DQ2/DQ8 (negative predictive)
- CD3/CD8 intraepithelial T cells
Clinical notes
- Adults often present atypically: anaemia, fatigue, bloating; children with diarrhoea, distension and failure to thrive after gluten enters the diet.
- Intraepithelial lymphocytosis and villous atrophy are not specific (viral enteritis, drugs), so histology and serology go together.
- Symptoms returning despite strict diet raise concern for refractory sprue or lymphoma.
Test yourself
Think of the answer, then tap the question to see it.
What does tissue transglutaminase do in the pathogenesis of coeliac disease?
It deamidates gluten peptides, increasing their binding to HLA-DQ2 or DQ8 and their presentation to CD4 T cells; it is also the target of IgA autoantibodies.
What is the most sensitive histological sign of coeliac disease?
Increased intraepithelial T lymphocytes, particularly in the villi.
Which serological test is most sensitive for coeliac disease?
IgA antibodies against tissue transglutaminase.
Which skin disease is associated with coeliac disease?
Dermatitis herpetiformis, an itchy blistering eruption.
Elsewhere in DurgiPedia
- Small intestine: villi, crypts, enterocytes, Paneth cells; duodenum vs jejunum vs ileum
- HLA associations with disease
- Type IV hypersensitivity (delayed, T cells)
- Autoantibodies: the table to know
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Celiac Disease (StatPearls (NCBI Bookshelf), 2025); Celiac disease - sprue: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2025).
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Representative model, for educational purposes only.