Review
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World J Gastroenterol. Jun 7, 2014; 20(21): 6495-6503
Published online Jun 7, 2014. doi: 10.3748/wjg.v20.i21.6495
Involvement of heat shock proteins in gluten-sensitive enteropathy
Erna Sziksz, Domonkos Pap, Gábor Veres, Andrea Fekete, Tivadar Tulassay, Ádám Vannay
Erna Sziksz, Tivadar Tulassay, Ádám Vannay, MTA-SE, Pediatrics and Nephrology Research Group, H-1083 Budapest, Hungary
Erna Sziksz, Domonkos Pap, Gábor Veres, Tivadar Tulassay, Ádám Vannay, First Department of Pediatrics, Semmelweis University, H-1083 Budapest, Hungary
Andrea Fekete, MTA-SE, “Lendulet” Diabetes Research Group, H-1083 Budapest, Hungary
Author contributions: Sziksz E and Vannay Á designed the concept for this review and wrote the manuscript; Pap D contributed to the literature search; Veres G, Fekete A and Tulassay T contributed to the final revision of the article; all authors approved the final version of the manuscript.
Supported by OTKA-84087/2010, -K81117, -K105530, -PD83431, -PD105361, “Lendulet” Research Grant LP2011-008, 2011 and KMR_12-1-2012-0074; Vannay Á and Veres G are holders of the János Bolyai Research Grant by János Bolyai Research Scholarship of the Hungarian Academy of Sciences
Correspondence to: Erna Sziksz, PhD, MTA-SE, Pediatrics and Nephrology Research Group, Bokay Janos utca 53-54, H-1083 Budapest, Hungary. sziksz.erna@med.semmelweis-univ.hu
Telephone: +36-1-3343186 Fax: +36-1-3138212
Received: November 21, 2013
Revised: February 12, 2014
Accepted: March 7, 2014
Published online: June 7, 2014
Processing time: 196 Days and 18.1 Hours
Abstract

Gluten-sensitive enteropathy, also known as coeliac disease (CD), is an autoimmune disorder occurring in genetically susceptible individuals that damages the small intestine and interferes with the absorption of other nutrients. As it is triggered by dietary gluten and related prolamins present in wheat, rye and barley, the accepted treatment for CD is a strict gluten-free diet. However, a complete exclusion of gluten-containing cereals from the diet is often difficult, and new therapeutic strategies are urgently needed. A class of proteins that have already emerged as drug targets for other autoimmune diseases are the heat shock proteins (HSPs), which are highly conserved stress-induced chaperones that protect cells against harmful extracellular factors. HSPs are expressed in several tissues, including the gastrointestinal tract, and their levels are significantly increased under stress circumstances. HSPs exert immunomodulatory effects, and also play a crucial role in the maintenance of epithelial cell structure and function, as they are responsible for adequate protein folding, influence the degradation of proteins and cell repair processes after damage, and modulate cell signalling, cell proliferation and apoptosis. The present review discusses the involvement of HSPs in the pathophysiology of CD. Furthermore, HSPs may represent a useful therapeutic target for the treatment of CD due to the cytoprotective, immunomodulatory, and anti-apoptotic effects in the intestinal mucosal barrier.

Keywords: Gluten-sensitive enteropathy; Coeliac disease; Heat shock proteins; Gluten-free diet; Intestinal barrier

Core tip: The only current effective therapy for the treatment of coeliac disease (CD) is a gluten-free diet. However, therapies targeting heat shock proteins (HSPs) for the treatment of various autoimmune disorders and cancers have been developed and have shown promising results. As CD is an autoimmune disorder, these new therapies may prove beneficial as an alternative treatment strategy. This review highlights and discusses recent data concerning the involvement of HSPs in the pathophysiology of CD.