Plasma Proteins Invariant to Diet in Celiac Disease: Results From a Proteomics Study on the UK Biobank

TL;DR

This study identifies two blood proteins that can detect celiac disease even when patients are on a gluten-free diet, which could improve diagnosis.

Contribution

The study discovers two plasma proteins invariant to diet that may serve as novel biomarkers for celiac disease.

Findings

Carboxypeptidase A2 and integrin subunit beta 7 were uniquely elevated in celiac disease patients on a gluten-free diet.

These proteins could serve as potential diagnostic markers independent of dietary status.

The findings suggest new possibilities for non-invasive celiac disease detection.

Abstract

Our serologic and pathologic markers of celiac disease normalize with a gluten-free diet. Identifying celiac disease in those who are already on a gluten-free diet is therefore difficult and currently requires a gluten challenge. The gluten challenge may have low sensitivity and is often not palatable to patients due to associated morbidity from gluten ingestion. We aimed to identify potential serologic markers of celiac disease invariant to diet by performing proteomic analysis.

We performed a proteomic analysis using the UK Biobank, specifically looking for plasma protein levels associated with celiac disease among individuals self-reporting a gluten-free diet. Celiac disease was identified through the ICD-10 code of K90.0. We limited our analysis to those diagnosed with celiac disease prior to proteomic data being collected. We inverse-rank normalized proteomic measurements. Our primary analysis was looking at differential expression between those diagnosed with celiac disease who reported being gluten-free and controls.

A total of 1044 individuals received a diagnosis of celiac disease prior to proteomic analysis. Of these individuals, 141 were administered a dietary questionnaire, and 132 reported being gluten-free. There were 4 proteins which were significantly higher in this group, however only two were unique to celiac disease: carboxypeptidase A2 and integrin subunit beta 7.

Although further diagnostic accuracy studies are required, this study identified 2 potential markers for celiac disease that are invariant to diet and commercially available. This has dramatic implications for clinical practice.

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