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utoimmunity is the downstream outcome of a rather extensive and coordinated series of events that include loss of self-tolerance, peripheral lymphocyte Aactivation, disruption of the blood-systems barriers, cellular infiltration into the target organs and local inflammation. Cytokines, adhesion molecules, growth factors, antibodies, and other molecules induce and regulate critical cell functions that perpetuate inflammation, leading to tissue injury and clinical phenotype. The nature and intensity of this response as well as the physiological ability to restore homeostasis are to a large extent conditioned by the unique amino acid sequences that define allelic variants on each of the numerous participating mol ecules. Therefore, the coding genes in their germline configuration play a primary role in determining who is at risk for developing such disorders, how the disease progresses, and how someone responds to therapy. Although genetic components in these diseases are clearly present, the lack of obvious and homogeneous modes of transmission has slowed progress by prevent ing the full exploitation of classical genetic epidemiologic techniques. Furthermore, autoimmune diseases are characterized by modest disease risk heritability and m- tifaceted interactions with environmental influences. Yet, several recent discoveries have dramatically changed our ability to examine genetic variation as it relates to human disease. In addition to the development of large-scale laboratory methods and tools to efficiently recognize and catalog DNA diversity, over the past few years there has been real progress in the application of new analytical and data-manage ment approaches.
Many developments in immunology have occurred over the past 10 years that give us a better understanding of the immune system and its dysfunctions. Refined mapping of the major histocompatibility complex MHC; elucidation of its gene structure and polymorphism, as well as the molecular basis of MHC restriction; the arrangement, expression, and regulation of immunoglobulins; definition of the structure of the T cell receptor and organization of its genes; and the characterization of soluble factors involved in cell/cell interactions and cloning of their genes are among the major accomplishments. Volumes I and II build on these developments in basic immunology to introduce animal models of various diseases, corresponding human studies, and the genetic analysis of autoimmune traits at the patient population level. The book will be a tremendous asset to immunologists, geneticists, and physicians in various areas of clinical subspecialties.
Many developments in immunology have occurred over the past 10 years that give us a better understanding of the immune system and its dysfunctions. Refined mapping of the major histocompatibility complex
Autoimmunity is one of the most highly investigated areas of immunologic research. The principle of immune system discrimination between self and foreign molecules is fundamental to the survival of the species, and the failure to establish or maintain this discrimination can lead to a wide spectrum of diseases. As a consequence of intensive studies, much has been learned with regard to the normal functioning of the immune system and the editing processes by which self-tolerance is established. Moreover, many theories and experimental models have been developed to explore the mechanisms of autoimmune disease pathogenesis. This book is the first volume of the new series 'Current Directions in Autoimmunity', which aims to consolidate current knowledge of autoimmunity focusing on both basic and clinical aspects. Given that these diseases have a strong genetic basis, it seems appropriate that the first volume addresses this topic. It reviews the most recent findings on genes affecting autoimmunity and genome-wide studies defining the multiple loci predisposing to prominent autoimmune diseases, such as lupus, arthritis, diabetes and multiple sclerosis. For each of these entities, studies in experimental models as well as humans are covered. The authoritative and timely material will be of interest to investigators in the fields of immunology and genetics, to clinicians with interest in rheumatology, endocrinology and neurology, and to those working to devise gene-specific therapies for a variety of inflammatory conditions.
This title provides an extremely helpful analysis of genes that may be associated with autoimmunity, and answers questions such as how these genes can be identified, and how the functions of the gene products can be elucidated. Incorporating data on disease-associated chromosomal loci that has been accumulated from inbred mice, the title: descibes how some susceptibility loci may be common to many diseases, whereas others are relatively disease specific discusses the importance of developing criteria for establishing the significance of these different categories of disease-associated loci.
The clinical management of autoimmune diseases has proven to be extremely difficult. Current therapies focus on trying to alleviate symptoms, but fail to correct the fundamental immune defects that lead to pathology. To achieve this goal, it is necessary to understand much of the biology of antigen presentation, lymphocyte activation and the effects of cytokines. The articles in this book provide an up-to-date review of current innovative therapies using both biologic and gene therapy for the treatment of selected autoimmune diseases. Therapeutical approaches discussed include oral tolerance, the use of anti-CD4 monoclonal antibodies, IL-10 and anti-TNFa antibodies, DNA vaccination, and gene therapy applied to organ-specific autoimmune disease. Although some of these techniques are still in their infancy, their potential efficacy has been demonstrated in several animal models of autoimmune disease, holding great promise for the future development of treatments. Written by recognized experts in the field, the chapters in this book illustrate the concept of technology transfer from bench to bedside and provide a valuable update for clinicians and scientists in clinical immunology.
Autoimmune diseases are common and often associated with considerable morbidity or - in diseases such as IDDM, myasthenia gravis and multiple sclerosis - mortality. In this volume, experts of international stature in basic science and clinical medicine with a common interest in understanding the normal and aberrant immune response present their experiences. It was their intention to fur- ther the understanding of potential clinical application of scientific observations and to help to comprehend the huge amount of results in autoimmunity research.
This book will address the growing roles of epigenetics in disease pathogenesis, and review the contribution of epigenetic modifications to disease onset and progression. The roles that epigenetics plays in facilitating effects of the environment on allergy and immunologic diseases will be reviewed. The book is divided into three parts – the first is an introduction to epigenetics and the methods that have been developed to study epigenetics, the second addresses epigenetics in allergic diseases and the third part will cover epigenetics in autoimmune diseases. With the rapid expansion of knowledge of how genes are regulated and how this regulation affects disease phenotypes, this book will be attractive to experienced researchers as well as those just launching an epigenetics research program. It will also be of interest to allergist, immunologists, rheumatologists and dermatologist who are engaged in clinical practice as a resource for understanding the basis for personalized and precision medicine. For example, the role that epigenetics plays in the pathogenesis in various allergic and autoimmune disorders and how this determines disease phenotypes will be covered extensively in this book. This book will thus help fill the gap in available resources on epigenetics in allergy and autoimmune diseases.
The Mosaic of Autoimmunity: The Novel Factors of Autoimmune Diseases describes the multifactorial origin and diversity of expression of autoimmune diseases in humans. The term implies that different combinations of factors in autoimmunity produce varying and unique clinical pictures in a wide spectrum of autoimmune diseases. Most of the factors involved in autoimmunity can be categorized into four groups: genetic, immune defects, hormonal and environmental factors. In this book, the environmental factors are reviewed, including infectious agents, vaccines as triggers of autoimmunity, smoking and its relationship with rheumatoid arthritis, systemic lupus erythematosus, thyroid disease, multiple sclerosis and inflammatory bowel diseases. An entirely new syndrome, the autoimmune/inflammatory syndrome induced by adjuvants (ASIA), is also included, along with other diseases that are now recognized as having an autoimmune etiopathogenesis. Highlights the concept of the mosaic of autoimmune manifestations Includes new visions on unsuspected molecules Provides updated knowledge to physicians helping patients with autoimmune diseases Presents thorough, up-to-date information on specific diseases, along with clinical applications