AUTOIMMUNE DISORDERS – PATHOGENETIC ASPECTS Edited by Clio P. Mavragani Autoimmune Disorders – Pathogenetic Aspects Edited by Clio P. Mavragani Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2011 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which permits to copy, distribute, transmit, and adapt the work in any medium, so long as the original work is properly cited. 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 Alenka Urbancic Technical Editor Teodora Smiljanic Cover Designer Jan Hyrat Image Copyright ZF, 2011. Used under license from Shutterstock.com First published September, 2011 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Autoimmune Disorders – Pathogenetic Aspects, Edited by Clio P. Mavragani p. cm. ISBN 978-953-307-643-0 free online editions of InTech Books and Journals can be found at www.intechopen.com Contents Preface IX Part 1 Pathogenesis of Systemic Autoimmune Disorders: Genetic and Enviromental Contributors 1 Chapter 1 Autoimmune Diseases: The Role of Environment and Gene Interactions 3 Wellington K. Ayensu, Emmanuel O. Keku, Raphael D. Isokpehi, Ibrahim O. Farah, Chris A. Arthur and Sophia S. Leggett Chapter 2 IRF-5 - A New Link to Autoimmune Diseases 35 Sujayita Roy and Paula M. Pitha Chapter 3 SLAM Family Receptors and Autoimmunity 53 Jordi Sintes, Ricardo Bastos and Pablo Engel Chapter 4 HLA and Citrullinated Peptides in Rheumatoid Arthritis 73 Iñaki Álvarez Chapter 5 Cell Surface Glycans at SLE – Changes During Cells Death, Utilization for Disease Detection and Molecular Mechanism Underlying Their Modification 89 Bilyy Rostyslav, Tomin Andriy, Yaroslav Tolstyak, Havrylyuk Anna, Chopyak Valentina, Kit Yuriy and Stoika Rostyslav Chapter 6 Regulatory T Cell Deficiency in Systemic Autoimmune Disorders – Causal Relationship and Underlying Immunological Mechanisms 111 Fang-Ping Huang and Susanne Sattler Chapter 7 Postinfectious Autoimmune Syndrome as a Key Factor in Chronization of the Infectious Disease 127 Natalia Cherepahina, Murat Agirov, Jamilyia Tabaksoeva, Kusum Ahmedilova and Sergey Suchkov VI Contents Chapter 8 Contribution of Peroxynitrite, a Reactive Nitrogen Species, in the Pathogenesis of Autoimmunity 141 Rizwan Ahmad and Haseeb Ahsan Chapter 9 Immunological Effects of Silica and Related Dysregulation of Autoimmunity 157 Naoko Kumagai, Hiroaki Hayashi, Megumi Maeda, Yoshie Miura, Hidenori Matsuzaki, Suni Lee, Yasumitsu Nishimura, Wataru Fujimoto and Takemi Otsuki Chapter 10 Gut Microbiota - “Lost in Immune Tolerance” 175 Serena Schippa and Valerio Iebba Part 2 Pathogenetic Aspects of Organ Specific Autoimmune Diseases 191 Chapter 11 Tolerance and Autoimmunity in Type 1 Diabetes 193 Valentina Di Caro, Nick Giannoukakis and Massimo Trucco Chapter 12 Immunogenetics of Type 1 Diabetes 221 Rajni Rani Chapter 13 Graves’ Disease - The Interaction of Lymphocytes and Thyroid Cells 245 Ben-Skowronek Iwona Chapter 14 Hashimoto’s Thyroiditis – Interactions of Lymphocytes, Thyroid Cells and Fibroblasts 257 Ben-Skowronek Iwona Chapter 15 Autoimmunity in Vitiligo 271 E. Helen Kemp, Sherif Emhemad, David J. Gawkrodger and Anthony P. Weetman Part 3 Comorbidities of Autoimmune Disorders 295 Chapter 16 Subclinical Atherosclerosis in Systemic Autoimmune Disorders 297 Giannelou M., Gravani F., Papadaki I., Ioakeimidis D. and Mavragani C.P. Chapter 17 Chronic Periaortitis as a Systemic Autoimmune Disease 319 Chang-Hee Suh Chapter 18 Endothelial Progenitor Cells: New Targets to Control Autoimmune Disorders 337 Sarah L. Brice, Andrew J. Sakko, Pravin Hissaria and Claudine S. Bonder Contents VII Chapter 19 Autoimmune Disorders and Lymphomas 355 Dolcetti R., Ponzoni M., Mappa S. and Ferreri A.J.M. Chapter 20 A Possible Link Between Autoimmunity and Cancer 403 Erika Cristaldi, Giulia Malaguarnera, Alessandra Rando and Mariano Malaguarnera Part 4 Immunology of Pregnancy 435 Chapter 21 Mechanism of Autoimmunity in Pregnancy - The Good and the Bad 437 Lotti Tajouri, Ekua W. Brenu, Donald R. Staines and Sonya M. Marshall-Gradisnik Chapter 22 T Lymphocyte Characteristics and Immune Tolerance During Human Pregnancy 463 Gergely Toldi, András Treszl and Barna Vásárhelyi Part 5 Osteoimmunology 487 Chapter 23 Osteoimmunology and Cancer - Clinical Implications 489 Evangelos Terpos, Maria Gkotzamanidou, Dimitrios Christoulas and Meletios A. Dimopoulos Preface The term “Autoimmune disorders” refers to a heterogeneous and multifaceted group of diseases which can affect virtually any organ system of the human body. They all arise from a misdirected attack of the organism’s immune defenses against ”self molecules” initially designed to protect them, resulting in chronic inflammation, autoantibody formation and tissue damage. They can be divided into systemic (response against ubiquitous self antigens) and organ-specific (against specific organs). Despite the unprecedented progress in the field of autoimmunity, the initial triggers for the aberrant immune reaction against “self” still remain to be defined. The interplay of environmental triggers, and an appropriate genetic makeup seem to be the prevailing belief for the pathogenesis of autoimmunity with many questions still unanswered. Furthermore, the contribution of autoimmune mechanisms in the generation of co-morbid conditions mainly manifested as cardiovascular burden or malignant transformation is currently a focus of intensive research. The present edition entitled “Autoimmune disorders - Pathogenetic aspects” aims to present the current available evidence of etiopathogenetic insights of both systemic and organ specific autoimmune disorders, the crossover interactions among autoimmunity, cardiovascular morbidity and malignancy, as well as novel findings in the exciting fields of osteoimmunology and immunology of pregnancy. We hope that this edition will provide a comprehensive overview of the recent advances in the field of autoimmunity, and at the same time foster further research efforts which will ultimately translate into better patient outcomes. Clio P. Mavragani, MD Department of Experimental Physiology, School of Medicine, University of Athens, Greece [...]... these individuals are 14 Autoimmune Disorders – Pathogenetic Aspects Fig 2 Results: HepG2 Genes affected by Mercury exposure genetically prone to develop spontaneous autoimmune diseases The etiology and pathogenicity of these, mostly systenic, autoimmune states have been difficult to trace Immunological findings support the notion that the origins of majority of these idiopathic autoimmune diseases can... NZM.C57Lc4 congenic strain) in lupus-prone NZM2328 mice with the appropriate genomic interval from a non -autoimmune genome led to the predicted and expected milder form of glomerulonephritis (Waters et al., 2004) Conversely 18 Autoimmune Disorders – Pathogenetic Aspects when the susceptible QTL was bred into a non -autoimmune genome such as B6.NZM2410.Sle1 mice, which carry the NZM2410-derivedSle1 QTL that showed... susceptibility; this reaffirms the clustering of functionally related H-2 and non-H-2 genes in the H-2 region on 16 Autoimmune Disorders – Pathogenetic Aspects chromosome 17 to be active players in the induction of SLE, a typical example of AD usually quoted Genetic variants do exist in autoimmune susceptibility that may be a basis for health disparity among races and forewarns that in dealing with xenobiotics... becoming a powerful tool or vehicle that is helping in the understanding the functional roles of the polymorphic alleles particularly those alleles 22 Autoimmune Disorders – Pathogenetic Aspects prevailing across ethnic groups Analyses of population differences in autoimmune state is a first and important step in unraveling the complexity of these genes affected by environmental pollutants represented by mercury... 1993; Puck JM, Sneller MC 1997) and in humans (Liossis et al 1996) It is suggested there is a genetic basis for airway hyperresponsiveness with linkage to chromosomes 5q, 11q (Li and 12 Autoimmune Disorders – Pathogenetic Aspects Wilson1997) and 12q24 in Hispanic subgroups (Salvato 2001) While MeIA is well characterized into different arrays of disease susceptibility in animal studies (De Raeve et al 1997)... consume more than 80% of the resources Consequently the cost to public health from clinical management of these conditions is on the increase All indications point to future better 4 Autoimmune Disorders – Pathogenetic Aspects management of asthmatics through research and interventional efforts directed at communities, hospitalizations and high-cost patients in order to decrease health care resource... toxicity (Oberdörster, 2004a and 2004b; Lovern and Klaper, 2005; Lam et al., 2004; Shvedovaet al., 2005; Fortner et al., 2005) of unknown physiological mechanisms and hence consequences 6 Autoimmune Disorders – Pathogenetic Aspects 2.1.2 Particulate matter Nanoparticles compare with particle pollution or particulate matter (PM), a group of complex mixture of extremely small air-borne particles and liquid... their precise etiology and/or the initiating factors Of late a small fraction of the T cells, the regulatory T cells are among the focal area of studies and have become recognized as 8 Autoimmune Disorders – Pathogenetic Aspects particularly crucial for control of autoreactive immune responses Normally the processing of a self antigen by the antigen presenting cells (APC) allow binding of processed antigenic... identified, these neurotoxicants need to come under regulatory practices in order to restrict their use and to control exposure as, for example in the case of lead (Silbergeld, 1997) 20 Autoimmune Disorders – Pathogenetic Aspects 5.2 Spontaneous lupus: who are at risk To date genetic mappings endorse genetic susceptibility to autoimmunity and confirms it to be highly associated with individuals with certain... risk in developing asthma Clinicians have known for quite a while that asthma is not a single disease Risk to asthma stems from early environmental factors as well as the presence of 10 Autoimmune Disorders – Pathogenetic Aspects susceptibility genes; subsequent disease induction and progression from inflammation as well as response to therapeutic agents plays big roles in disease etiology It is a typical . AUTOIMMUNE DISORDERS – PATHOGENETIC ASPECTS Edited by Clio P. Mavragani Autoimmune Disorders – Pathogenetic Aspects Edited by Clio P. Mavragani. entitled Autoimmune disorders - Pathogenetic aspects aims to present the current available evidence of etiopathogenetic insights of both systemic and organ specific autoimmune disorders, . www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Autoimmune Disorders – Pathogenetic Aspects, Edited by Clio P. Mavragani p. cm. ISBN 978-953-307-643-0 free