The primary objectives are: * Characterize the T cell receptor (TCR) repertoire in duodenal biopsy samples of participants pre- and post-challenge. * Compare for each patient the TCR repertoire of duodenal biopsy samples with the peripheral blood TCR repertoire of each study participant * Characterize the transcriptome of duodenal biopsy samples and blood from study participants pre- and post-challenge The secondary objectives are: * Ex vivo identification and validation of DQ-restricted gliadin specific TCRs. * Characterize the gluten-challenge induced changes in small intestine histology using standard for Celiac Disease (CeD) histological assessments
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
24
Administered orally daily for 14 days
Celiac Research Centre Mass General Hospital
Boston, Massachusetts, United States
Change from Baseline in small intestine TCR repertoire
Change in the T-cell receptor repertoire (measured by T cell receptor sequencing) in the small intestine after gluten challenge
Time frame: Up to 30 days post challenge
Change from Baseline in peripheral blood TCR repertoire
Change in the T-cell receptor repertoire (measured by T cell receptor sequencing) in peripheral blood after gluten challenge
Time frame: Up to 30 days post challenge
Changes from baseline in small intestine and peripheral blood transcriptome
Change in the gene expression profile (transcriptomic analysis by ribonucleic acid \[RNA\] sequencing and cellular indexing of transcriptomes and epitopes by sequencing \[CITEseq\]) of the small intestine and peripheral blood after gluten challenge
Time frame: Up to 30 days post challenge
Change from Baseline in Small Intestine Histology Based on Intraepithelial Lymphocytes (IEL) Count per 100 epithelial cells
IELs are white blood cells (WBCs) interspersed between epithelial cells of the small and large intestine where they function to preserve the integrity of the mucosal barrier by protecting the epithelium against pathogen or immune-induced pathology. Increased IELs count indicated more extreme CeD disease symptoms. Baseline values are defined as the last observed value before the first dose of gluten.
Time frame: Baseline and Day 15
Change from Baseline in Small Intestine Histology Based on Villous Height (Microns), Crypt Depth (Microns) and Villous Height to Crypt Depth Ratio (Vh:Cd)
Villi are the small finger like projections that line the small intestine and promote nutrient absorption and are often shortened in active CeD. Crypts are grooves between the villi that are often elongated in CeD. A decreased Vh:Cd ratio indicates more extreme CeD disease symptoms. Baseline values (Microns) will be defined as the last observed value before the first dose of gluten.
Time frame: Baseline and Day 15
Identification and ex vivo functional validation of gluten-specific T cells
Clonality of peripheral blood mononuclear cell (PBMC)-derived gluten-specific T cells (measured by T cell receptor sequencing) after ex vivo expansion with gluten peptides
Time frame: Up to 30 days post challenge
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