An updated overview on celiac disease: from immuno-pathogenesis and immuno-genetics to therapeutic implications

ABSTRACT

Introduction

Celiac disease (CD) is an autoimmune enteropathy triggered by ingestion of gluten. While presenting many similarities with other autoimmune diseases, celiac disease is unique in that the external trigger, gluten, and the genetic background necessary for disease development (HLA DQ2/DQ8) are well described. The prevalence of celiac disease is dramatically increasing over the years and new epidemiologic data show changes regarding age of onset and symptoms. A better understanding of CD-pathogenesis is fundamental to highlight the reasons of this rise of celiac diagnoses.

Areas covered

In this review we describe CD-pathogenesis by dissecting all the components necessary to lose tolerance to gluten (ingestion of gluten, genetic predisposition, loss of barrier function and immune response). Additionally, we also highlight the role that microbiome plays in celiac disease as well as new proposed therapies and experimental tools.

Expert opinion

Prevalence of autoimmune diseases is increasing around the world. As a result, modern society is strongly impacted by a social and economic burden. Given the unique characteristics of celiac disease, a better understanding of its pathogenesis and the factors that contribute to it may shed light on other autoimmune diseases for which external trigger and genetic background are not known.

KEYWORDS:

• Celiac disease
• immune response
• barrier function
• gluten
• hla
• microbiome
• autoimmunity
• immunogenetics

Article highlights

• Celiac disease prevalence is increasing over the last decades, therefore suggesting that additional factors, other than gluten ingestion and correct genetic background, contribute to loss of tolerance to gluten.

• Given its unique characteristics, celiac disease can be ‘used’ as a model of autoimmunity to shed light on other autoimmune diseases.

• GWAS studies and RNAseq analyses have broadened the knowledge on genetic factors contributing to celiac disease onset.

• Immune response characterizing celiac disease pathogenesis is complex and each step, from innate immune response to ineffective suppression of T cells, is crucial to mount chronic inflammation.

• New experimental tools have been recently proposed to deeply investigate the different steps of celiac pathogenesis.

• The rising number of refractory celiac patients and the socio economic impact that following a gluten free diet has on patients, pushed the scientific community to find new therapies to treat celiac patients.

Declaration of interest

AF is a stockholder at Alba Therapeutics, serves as a consultant for Inova Diagnostics and

Innovate Biopharmaceuticals, is an advisory board member for Axial Biotherapeutics and

Ubiome, and has a speaker agreement with Mead Johnson Nutrition. All other authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.