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Spatial tissue proteomics analysis of laser capture microdisscted intestinal crypt compartment in celiac disease

ABSTRACT: Crypt hyperplasia is a key feature of celiac disease and various other small intestinal inflammatory conditions. By undertaking mass spectrometry-based tissue proteomics of the gut epithelial crypt zone, we found that active celiac disease is characterized by a strong interferon-γ (IFN-γ) signal. This signal, hallmarked by increased expression of MHC molecules, coincides with a markedly reduced expression of proteins associated with fatty acid metabolism. This dataset contains protoemics analysis of crypt comparment samples isolated by laser capture microdissection of tissue sections from FFPE duodenal gut biopsies from human subjects with and without celiac disease.

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ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Duodenum

SUBMITTER: Jorunn Stamnaes

LAB HEAD: Jorunn Stamnæs

PROVIDER: PXD062610 | Pride | 2025-08-08

REPOSITORIES: Pride

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Project description:Coeliac disease is a small intestinal disorder caused by an abarrent immune response towards dietary gluten due to activation of pro-inflammatory gluten specific CD4+ T cells. Histological evaluation and classification of gluten induced musosal changes is part of the diagnostic work up. of adults. The kinetics of mucosal recovery following commencesment of a gluten free diet (disease remission) and the degree of mucosal changes induced by gluten reintroduction (gluten challenge) varies between patients. Also, patients classified with similar clinical and histological disease remission, can develop different degree of mucosal damage following the same gluten challenge regime. This variation poses a challenge for the interpretation of gluten induced mucosal changes both in a diagnostic and clinical trial settings. In this study, we have analysed material from small intestinal biopsies collected from 19 treated coeliac disease patients before and after completion of a 14-day oral gluten challenge. These patients are part of a previoslpreviouslyu described study where all patients were in clinical and mucosal remission at baseline but only some patients developed histological changes in the mucosa in response to gluten. We have performed shotgun LC-MSMS analysis and label-free quantification of total gut tissue and from laser capture microdissected epithelial cell layer samples. We found that differences in tissue proteome expression could separate patients as responders and non-responders to the gluten challenge. Patients whoich responded strongly to gluten , had signs of gut inflammation already at baseline, supported by presence of low-level blood inflammatory parameters and a slight increase in numbers of gluten-specific CD4+ T cells at baseline. Our proteomics analysis demonstrated baseline differences in gut tissue state between patients that were not evident from routine clinical and histological evaluation. These baseline differences likely explains why some patients respond more strongly to gluten challenge than others.

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Spatial tissue proteomics analysis of laser capture microdisscted intestinal crypt compartment in celiac disease

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