Genome-wide analysis of B and T cell gene expression during a six-week gluten challenge in patients with celiac disease

Dietary gluten proteins (prolamins) from wheat, rye, and barley are the driving forces behind celiac disease, an organ-specific autoimmune disorder that targets both the small intestine and organs outside the gut. In the small intestine, gluten induces inflammation and a typical morphological change of villous atrophy and crypt hyperplasia. Gut lesions improve and heal when gluten is excluded from the diet and the disease relapses when patients consume gluten. Oral immune tolerance towards gluten may be kept for years or decades before breaking tolerance in genetically susceptible individuals. Celiac disease provides a unique opportunity to study autoimmunity and the transition in immune cells as gluten breaks oral tolerance. Seventy-three celiac disease patients on a long-term gluten-free diet ingested a known amount of gluten daily for six weeks. A peripheral blood sample and intestinal biopsies were taken before and six weeks after initiating the gluten challenge. Biopsy results were reported on a continuous numeric scale that measured the villus height to crypt depth ratio to quantify gluten-induced gut mucosal injury. Pooled B and T cells were isolated from whole blood, and RNA was analyzed by DNA microarray looking for changes in peripheral B- and T-cell gene expression that correlated with changes in villus height to crypt depth, as patients maintained or broke oral tolerance in the face of a gluten challenge.

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Garber ME, Saldanha A, Parker JS, Jones WD, Kaukinen K, Laurila K, Lähdeaho ML, Khatri P, Khosla C, Adelman DC, Mäki M