causes
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Celiac disease requires three converging factors: a gluten-containing diet, genetic predisposition (HLA-DQ2/DQ8), and environmental triggers.
The Trigger: Gluten
Gluten refers to proteins in:
- Wheat (gliadin, glutenin) — including subspecies: spelt, durum, khorasan, and hybrids like triticale
- Barley (hordein)
- Rye (secalin)
- Oats (avenin) — small subset of patients react; controversial due to cross-contamination and genetic variability
Safe grains / foods: maize, millet, sorghum, teff, rice, wild rice, amaranth, quinoa, buckwheat, potatoes, bananas.
Regulatory standard: Products must have <20 ppm gluten to be labelled gluten-free. Tolerable individual thresholds vary (~10–35 mg/day).
Genetic Predisposition: HLA-DQ
Almost all celiac patients carry HLA-DQ2 or, less commonly, HLA-DQ8:
| Allele | Prevalence in celiac |
|---|---|
| HLA-DQ2 (DQ2.5 haplotype) | ~95% |
| HLA-DQ8 | Most of the remaining ~5% |
| Neither | ~2% |
Key caveat: ~40% of the general population also carries HLA-DQ2 or DQ8 without developing celiac disease. The alleles are necessary but not sufficient.
HLA-DQ2.5 Detail
- Encoded by DQA10501 and DQB10201
- Inheriting from both parents (homozygous) = highest risk + more severe complications
- Frequency varies geographically; more common in areas with long wheat-eating history
Why These Alleles Matter Mechanistically
HLA-DQ is part of the MHC class II antigen-presenting system. DQ2/DQ8 variants bind gluten-derived peptides with unusually high affinity (especially after modification by tissue transglutaminase), facilitating T cell activation. See mechanism.
Environmental Risk Modifiers
Even with HLA-DQ2/DQ8, additional environmental factors influence onset:
- Infections (viral, bacterial)
- Gut microbiome composition
- Timing of gluten introduction in infancy (large early amounts may increase risk in predisposed individuals)
- Geographic latitude
- Birth weight
- Antibiotic use
- Breastfeeding
- Socioeconomic status / hygiene
Oats: A Special Case
Most patients tolerate uncontaminated "pure" oats. Issues arise from:
- Cross-contamination with wheat/barley during processing
- Immunoreactivity to avenin in a small subset
- Genetic variability between oat cultivars
- Possible dietary intolerance independent of autoimmunity
Clinical guidelines differ on whether celiac patients should consume oats. See oats for the dedicated synthesis page.
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