Tài liệu Celiac Disease – From Pathophysiology to Advanced Therapies Edited by Peter Kruzliak and

CELIAC DISEASE – FROM

PATHOPHYSIOLOGY TO

ADVANCED THERAPIES

Edited by Peter Kruzliak and Govind Bhagat

Celiac Disease – From Pathophysiology to Advanced Therapies

Edited by Peter Kruzliak and Govind Bhagat

Published by InTech

Janeza Trdine 9, 51000 Rijeka, Croatia

Copyright © 2012 InTech

All chapters are Open Access distributed under the Creative Commons Attribution 3.0

license, which allows users to download, copy and build upon published articles even for

commercial purposes, as long as the author and publisher are properly credited, which

ensures maximum dissemination and a wider impact of our publications. After this work

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any publication of which they are the author, and to make other personal use of the

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As for readers, this license allows users to download, copy and build upon published

chapters even for commercial purposes, as long as the author and publisher are properly

credited, which ensures maximum dissemination and a wider impact of our publications.

Notice

Statements and opinions expressed in the chapters are these of the individual contributors

and not necessarily those of the editors or publisher. No responsibility is accepted for the

accuracy of information contained in the published chapters. The publisher assumes no

responsibility for any damage or injury to persons or property arising out of the use of any

materials, instructions, methods or ideas contained in the book.

Publishing Process Manager Romina Skomersic

Technical Editor Teodora Smiljanic

Cover Designer InTech Design Team

First published July, 2012

Printed in Croatia

A free online edition of this book is available at www.intechopen.com

Additional hard copies can be obtained from [email protected]

Celiac Disease – From Pathophysiology to Advanced Therapies,

Edited by Peter Kruzliak and Govind Bhagat

p. cm.

ISBN 978-953-51-0684-5

Contents

Preface IX

Section 1 New Insights on Pathophysiology of Celiac Disease 1

Chapter 1 Mucosal Expression of Claudins in Celiac Disease 3

Dorottya Nagy-Szakál, Hajnalka Győrffy, Katalin Eszter Müller,

Kriszta Molnár, Ádám Vannay, Erna Sziksz, Beáta Szebeni,

Mária Papp, András Arató and Gábor Veres

Chapter 2 Antioxidant Status of the Celiac Mucosa:

Implications for Disease Pathogenesis 17

Vesna Stojiljković, Jelena Kasapović, Snežana Pejić,

Ljubica Gavrilović, Nedeljko Radlović, Zorica S. Saičić

and Snežana B. Pajović

Chapter 3 Heat Shock Proteins in Coeliac Disease 37

Erna Sziksz, Leonóra Himer, Gábor Veres, Beáta Szebeni,

András Arató, Tivadar Tulassay and Ádám Vannay

Section 2 Clinical Manifestations

and Complications of Celiac Disease 69

Chapter 4 Celiac Disease and Diabetes Mellitus Type 1 71

Mieczysław Szalecki, Piotr Albrecht and Stefan Kluzek

Chapter 5 Hematologic Manifestations of Celiac Disease 83

Peter Kruzliak

Chapter 6 Multiple Sclerosis and Celiac Disease 101

Carlos Hernández-Lahoz and Luis Rodrigo

Section 3 Detection of Cereal Toxic Peptides

Based on New Laboratory Methods 113

Chapter 7 Sensitive Detection of Cereal Fractions that

Are Toxic to Coeliac Disease Patients, Using Monoclonal

Antibodies to a Main Immunogenic Gluten Peptide 115

Carolina Sousa, Ana Real, Mª de Lourdes Moreno

and Isabel Comino

VI Contents

Section 4 Advanced Therapies in Celiac Disease 137

Chapter 8 Enzyme Therapy

for Coeliac Disease: Is it Ready for Prime Time? 139

Hugh J. Cornell and Teodor Stelmasiak

Section 5 Follow-up of Patients with Celiac Disease 165

Chapter 9 Principles and Strategies

for Monitoring Individuals with Celiac Disease 167

Mohsin Rashid

Chapter 10 On Treatment Outcomes

in Coeliac Disease Diagnosed in Adulthood 179

Claes Hallert and Susanne Roos

Preface

Celiac Disease (CD) or Gluten Sensitive Enteropathy (GSE) is a life‐long disorder. It is

characterized by inflammation in the small intestine of genetically predisposed

individuals caused by inappropriate immune response to gluten, a protein enriched in

some of our common grains (wheat, rye and barley). The toxicity of gluten is

manifested by the autoimmune action of T‐lymphocytes on mucosal cells in the small

intestine, disrupting its vital function of absorbing  

nutrients from food. Epidemiological studies conducted during the past decade

revealed that CD is one of the most common lifelong disorders worldwide. CD can

manifest with a previously unsuspected range of clinical presentations, including the

typical malabsorption syndrome and a spectrum of symptoms potentially affecting

any organ system. Since CD is often atypical or even silent on clinical ground, many

cases remain undiagnosed and exposed to the risk of long term complications, such as

anemia and other hematological complications, osteoporosis, neurological

complications or cancer.  

In recent years, there have been noticeable shifts in the age of onset of symptoms and

in the clinical presentation of CD, changes that seem to be associated with a delayed

introduction of gluten coupled with its reduced amount in the complications in the

diet. Another controversial topic concerns the complications of untreated CD. Multiple

studies that have focused on the biochemistry and toxicity of gluten‐containing grains

and the immune response to these grains suggest that individuals affected by CD

should be treated,    irrespective of the presence or absence of symptoms and/or

associated conditions.  Nevertheless, there is general agreement that the persistence of

mucosal injury, with or without typical symptoms, can lead to severe complications in

CD patients who do not strictly comply with a gluten‐free diet.

Research into gluten sensitivity has never been more popular nor more exciting. With

regard to gluten sensitivity we are in a period of great change occasioned by the

application of new methods to identify gluten sequences as T‐cell antigens, the study

of genetic and mollecular pathophysiology,  the use of  immunohistocytochemical and

mRNA probing response to gluten and the research of future therapeutic options.

This book covers most of the aforementioned controversial and yet unresolved topics

by including the contributions of experts in CD. What the reader will surely find

X Preface

stimulating about this book is not only its exhaustive coverage of our current

knowledge of CD, but also provocative new concepts in disease pathogenesis and

treatment.

To do this book would have been impossible without the contributions of friends and

colleagues from around the world who have devoted so much interest to the project. It

has also been necessary for them to master the unique chapter‐writing skills required

of every manuscript in this book. This projet would not have been possible without the

expertise and invaluable contribution and technical support of Ms. Romina Skomersic

and Ms. Natalia Reinic and of the InTech publishing team.

It has been a privilege to put together „Celiac Disease  ‐  From Pathophysiology to

Advanced Therapies“ that is offered in the hope that its pages will contain the

necessary information for researches, gastroenterologists, physicians, and others who

are interested in this field of medicine and science.  

Even if I do not give you any big answers in this book, I am still proud that you are

holding it in your hands. It is because I learned, during my time as an editor and

author of this book, that even if we do not reach the endpoint of our journey, we can

still make a great contribution travelling to it.  

Peter Kruzliak, M.D., BSc.

5th Department of Internal Medicine

University Hospital and Medical Faculty of Comenius University

Bratislava,  

Slovakia

Section 1

New Insights on Pathophysiology

of Celiac Disease

1

Mucosal Expression of Claudins

in Celiac Disease

Dorottya Nagy-Szakál1, Hajnalka Győrffy2, Katalin Eszter Müller1,

Kriszta Molnár1, Ádám Vannay1,3, Erna Sziksz1,3, Beáta Szebeni1,3,

Mária Papp4, András Arató1 and Gábor Veres1

1First Department of Pediatrics, Semmelweis University, Budapest, 2Second Department of Pathology, Semmelweis University, Budapest,

3Research Group for Pediatrics and Nephrology, Semmelweis University

and Hungarian Academy of Sciences, Budapest,

4Department of Medicine, University of Debrecen,

Hungary

1. Introduction

Celiac disease is an autoimmune gluten-sensitive enteropathy or nontropical sprue

occurring in genetically susceptible individuals, triggered by dietary gluten and related

prolamins, which damage small intestine and interfere with absorption of nutrients. Tight

junctions play an important role in the pathomechanism of different gastrointestinal

diseases. Claudins, the main tight junction proteins are found in the monolayer of the

gastrointestinal epithelium (Bornholdt et al., 2011). The presence and distribution of claudin

depend on the organs and the function of the tissues (Gonzales-Mariscal et al., 2003). The

expression levels of various claudins correlate to the distinct physiological and pathological

conditions. Claudins modulate the permeability of the epithelial barrier (Bornholdt et al.,

2011). Surprisingly, there is only one study analyzing different claudins at protein level of

intestinal biopsies in patients with celiac disease. At first, general information of tight

junctions and the characteristics of claudins in different gastrointestinal disorders will be

highlighted for a better understanding of the role of claudins in celiac disease.

2. Characteristics of tight junctions

Intercellular junctions are presented in multicellular organism as linking cells and

maintaining barrier function between the two sides of cell layer (Staehelin et al., 1974). It

plays a structural role in maintaining biological compartments, cell polarity, and a barrier

function separating the internal and external environments (Krause et al., 2008). It also

controls the paracellular transport (Balda et al., 1996). The barrier and fence function are

dynamically changing and guide cell behavior. Three major types of intercellular junctions

are the zonula occludens (tight junction), the zonula adherens (adherens junction) and the

macula adherens (desmosome). The tight junction is an intercellular junction by interlinked

rows of integral membrane proteins limiting the intercellular transport. One of the most

important components of tight junction is claudin (Figure 1).