Not an Intolerance — An Autoimmune Disease
Coeliac disease is frequently confused with food intolerance, but the distinction is critical. It is a systemic autoimmune condition triggered by gluten — a storage protein found in wheat, barley, and rye — in genetically susceptible individuals. Unlike food intolerance, which produces functional symptoms without tissue damage, coeliac disease causes immune-mediated destruction of the small intestinal mucosa, leading to villous atrophy, crypt hyperplasia, and malabsorption.
The Genetic Prerequisite
Approximately 95 percent of coeliac patients carry the HLA-DQ2 haplotype, and most of the remainder carry HLA-DQ8. These human leukocyte antigen molecules present deamidated gliadin peptides to CD4+ T cells in the lamina propria, initiating an adaptive immune response. However, roughly 30 percent of the general population carries HLA-DQ2 or DQ8, yet only 1 percent develops coeliac disease — indicating that additional genetic and environmental triggers (infections, infant feeding patterns, microbiome composition) are necessary.
The Tissue Transglutaminase Connection
The enzyme tissue transglutaminase (tTG) deamidates gliadin peptides, converting glutamine residues to glutamic acid and increasing their binding affinity for HLA-DQ2/DQ8 molecules. The immune system produces antibodies against both the deamidated gliadin and against tTG itself — making anti-tTG IgA the primary serological screening test for coeliac disease, with sensitivity and specificity both exceeding 95 percent in IgA-sufficient individuals.
Why Testing Before Diet Change Matters
Once gluten is removed from the diet, antibody levels fall and mucosal healing begins — which means that serological testing and duodenal biopsies performed after starting a gluten-free diet (GFD) may produce false-negative results. This is one of the most common diagnostic pitfalls: patients self-initiate a GFD based on symptoms, feel better, and then cannot be accurately tested. Guidelines unanimously recommend that coeliac disease must be excluded while the patient is still consuming gluten.
Beyond the Gut
Coeliac disease is not purely a gastrointestinal condition. Extraintestinal manifestations include dermatitis herpetiformis (an intensely pruritic blistering skin rash), iron-deficiency anaemia refractory to oral supplementation, osteoporosis, peripheral neuropathy, cerebellar ataxia, liver enzyme elevation, and reproductive complications. Some patients present with no gastrointestinal symptoms at all — so-called "silent coeliac disease" — detected incidentally through screening of at-risk groups.
The Gluten-Free Diet: Treatment, Not Trend
A strict, lifelong GFD is the only established treatment for coeliac disease. It requires eliminating all sources of wheat, barley, and rye — including hidden sources in sauces, processed foods, medications, and communion wafers. Adherence is challenging: studies show that even patients who believe they are fully compliant have inadvertent gluten exposure. Emerging therapies — including gluten-degrading enzymes, tight-junction modulators (larazotide acetate), and immunomodulatory approaches — are in clinical trials but none has yet received approval.