Transcriptomics,Genomics

Dataset Information

26

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


ABSTRACT: 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. Overall design: Whole blood sample were taken before and six weeks after a gluten challenge in 73 patients with celiac disease. B and T cells were purified from whole blood using anti-CD3 and anti-CD19 conjugated magnetic beads. Total RNA obtained from the purified pool of B and T cells was used for DNA microarray analysis using the Illumina platform.

INSTRUMENT(S): Illumina HumanHT-12 V3.0 expression beadchip

SUBMITTER: Mitchell E Garber  

PROVIDER: GSE87629 | GEO | 2017-01-27

SECONDARY ACCESSION(S): PRJNA345434

REPOSITORIES: GEO

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Publications

A B-Cell Gene Signature Correlates With the Extent of Gluten-Induced Intestinal Injury in Celiac Disease.

Garber Mitchell E ME   Saldanha Alok A   Parker Joel S JS   Jones Wendell D WD   Kaukinen Katri K   Laurila Kaija K   Lähdeaho Marja-Leena ML   Khatri Purvesh P   Khosla Chaitan C   Adelman Daniel C DC   Mäki Markku M  

Cellular and molecular gastroenterology and hepatology 20170128 1


Celiac disease (CeD) provides an opportunity to study autoimmunity and the transition in immune cells as dietary gluten induces small intestinal lesions.Seventy-three celiac disease patients on a long-term, gluten-free diet ingested a known amount of gluten daily for 6 weeks. A peripheral blood sample and intestinal biopsy specimens were taken before and 6 weeks after initiating the gluten challenge. Biopsy results were reported on a continuous numeric scale that measured the villus-height-to-cr  ...[more]

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