CELIACDISEASE–FROM PATHOPHYSIOLOGYTO ADVANCEDTHERAPIES EditedbyPeterKruzliakandGovindBhagat 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 has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. 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 orders@intechopen.com 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 CeliacDisease(CD)orGlutenSensitiveEnteropathy(GSE)isalife‐longdisorder.Itis characterized by inflammation in the small intestine of genetically predisposed individualscausedbyinappropriateimmuneresponsetogluten,aproteinenrichedin some of our common grains (wheat, rye and barley). The toxicity of gluten is manifestedbytheautoimmune actionofT‐lymphocytesonmucosalcellsinthesmall intestine,disruptingitsvitalfunctionofabsorbing 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 previouslyunsuspected range of clinical presentations,includingthe typical malabsorption syndrome and a spectrum of symptoms potentially affecting any organ system. Since CD is oftenatypical or even silent on clinical ground, many casesremainundiagnosed andexposedtotheriskoflongtermcomplications,suchas anemia and other hematological complications, osteoporosis, neurological complicationsorcancer. Inrecentyears,therehavebeennoticeableshiftsintheageofonsetofsymptomsand 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 controversialtopicconcernsthecomplicationsofuntreatedCD.Multiple studiesthathavefocusedonthebiochemistryandtoxicityofgluten‐containinggrains 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 associatedconditions.Nevertheless, thereisgeneralagreementthatthepersistenceof mucosalinjury,withorwithouttypicalsymptoms,canleadtoseverecomplicationsin CDpatientswhodonotstrictlycomplywithagluten‐freediet. Researchintoglutensensitivityhasneverb eenmorepopularnormoreexciting.With regard to gluten sensitivity we are in a period of great change occasioned by the applicationof new methods toidentify glutensequences as T‐cellantigens, thestudy ofgenetic andmollecularpathophysiology,theuseofimmunohistocytochemicaland mRNAprobingresponsetoglutenandtheresearchoffuturetherapeuticoptions. Thisbookcovers mostof theaforementioned controversialandyet 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. Todothisbookwouldhavebeenimpossiblewithoutthecontributionsoffriendsand colleaguesfromaroundtheworldwhohavedevotedsomuchinterest totheproject.It hasalsobeennecessary forthem to masterthe uniquechapter‐writing skills required ofeverymanuscriptinthisbook.Thisprojetwouldnothavebeenpossiblewithoutthe expertiseandinvaluablecontributionandtechnicalsupportofMs.RominaSkomersic andMs.NataliaReinicandof theInTechpublishingteam. 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 areinterestedinthisfieldofmedicineandscience. Even if I do not give you any big answers inthis 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 authorofthis book,that even if wedonot reach theendpoint ofour journey,we can stillmakeagreatcontributiontravellingtoit. PeterKruzliak,M.D.,BSc. 5thDepartmentofInternalMedicine UniversityHospitalandMedicalFacultyofComeniusUniversity Bratislava, Slovakia . CELIAC DISEASE – FROM PATHOPHYSIOLOGY TO ADVANCED THERAPIES EditedbyPeterKruzliakandGovindBhagat Celiac Disease – From Pathophysiology to Advanced Therapies. Claudin, GIST: gastrointestinal stromal tumour, IBD: inflammatory bowel disease) Celiac Disease – From Pathophysiology to Advanced Therapies 8 Since the damage of the cell-cell adhesion. required ofeverymanuscriptinthisbook.Thisprojetwouldnothavebeenpossiblewithoutthe expertiseandinvaluablecontributionandtechnicalsupportofMs.RominaSkomersic andMs.NataliaReinicandof theInTechpublishingteam. It has been a privilege to put together Celiac Disease ‐ From Pathophysiology to Advanced Therapies that is offered in the hope that its pages