Pathogenic mechanisms and clinical relevance of autoantibodies

For many autoantibodies, a direct pathogenic effect and the mechanism, whereby they cause damage has already been proven. Some established or postulated mechanisms of autoantibody-mediated tissue damage include binding to surface membranes and subsequent destruction of the cell, binding to cell surface receptors and subsequent modification of cell biological activity without cytolysis, immune complex formation and tissue localization, translocation of intracellular antigens to cell membrane, penetration into living cells and binding to extracellular molecules. Although certain autoantibodies probably have no pathogenic effects and the pathogenic mechanisms for certain others are unclear, a direct role for autoantibody-mediated injury is possible or likely for many other autoantibodies. Furthermore, although the detection of some autoantibodies only reflects the presence to some extent of nonspecific autoimmune response (.that is antinuclear antibodies), the finding of many others has a paramount clinical relevance, either as diagnostic tools or for monitoring disease activity, or as both, and even for prediction of outcome. The scope of this book illustrates the important role that the demonstration of many autoantibodies has assumed in the diagnosis and monitoring of human disease. It has even become impossible to establish the diagnosis of many diseases, such as systemic lupus erythematosus (SLE) or the antiphospholipid syndrome (APS), in the absence of the relevant autoantibodies. The chapter reviews the different established or postulated mechanisms of autoantibody-mediated tissue damage.