Autoimmune diseases affect 3-5% of the population, but they attract medical attention only when they become sustained and cause lasting tissue damage . Depending on the affected organ, the clinical presentation of autoimmune diseases can be very heterogeneous and specific, or unspecific features can predominate. A common characteristic of autoimmune diseases is the presence of autoantibodies that are produced by autoreactive lymphocytes and that may be the direct cause of some of these disorders. For instance, in Graves' disease, autoantibodies bind to and stimulate the receptor for thyrotropin, resulting in unrestrained thyrocyte growth, excessive thyroid hormone production, and diffuse hyperplasia of the thyroid gland [2, 3]. In Hashimoto's thyroiditis, antibodies against thyroglobulin, thyroid peroxidase, and the thyrotropin receptor have been suggested to play a role in the progressive destruction of thyroid follicular cells [4, 5]. In pemphigus vulgaris, autoantibodies against the epidermal adhesion molecule desmoglein 3 disrupt the epidermis .
Although the pathogenic role played by autoantibodies is well characterized in these diseases, the cellular and molecular mechanisms underlying the initiation and the propagation of the autoimmune response remain unknown. Moreover, organ-specific damage by autoantibodies might not be sufficient to explain the progression or chronicity of an autoimmune disease. For instance, autoimmune gastritis is characterized by the production of parietal cell autoantibodies that are reactive with the alpha- and beta-subunits of the gastric H/K ATPase. However, experimental data of a murine (neonatal thymectomy) autoimmune gastritis model indicated that this autoimmune disease is mediated by CD4+ T cells and not by organ-specific autoantibodies [7, 8]. Furthermore, in a variety of autoimmune diseases, such as lupus erythematosus, autoantibodies are not directed against organ-specific structures but react with widely distributed intracellular antigens.
Autoantibodies against intracellular antigens have been implicated as usually not pathogenic and instead have been viewed largely as secondary consequences of the autoimmune process. This view has also been restricted recently: in a murine model of autoimmune arthritis, the transfer of IgG from diseased animals induced arthritis in healthy recipients . These pathogenic autoantibodies bind to glucose-6-phosphate isomerase, a ubiquitous intracellular antigen .
In summary, autoimmunity is mediated by both direct (autoantibody-asso-ciated) and indirect (cytokine-associated) immune response mechanisms. Depending on the respective autoimmune disease, one of those mechanisms may predominate. Thus, often the specificity of the autoantibodies does not correlate with clinical profiles, as exemplified by the autoimmune liver diseases. This chapter therefore deals with the relevance of autoantibodies for the diagnosis and natural history of autoimmune liver diseases including autoimmune hepatitis, primary biliary cirrhosis, and overlap syndrome.
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