Immunologic Disorders: Autoimmunity: Genetics and Immunologic Mechanisms

Autoimmune diseases, whether the immunopathology is mediated by T cells or antibodies, represent a failure of the normal mechanisms that maintain immunologic homeostasis in response to specific antigens. Environmental as well as genetic factors are involved in initiating autoimmunity. Many of the genes specifying components of the immune system are polymorphic and are likely to lead to variation in specific immune responses to foreign and self antigens and the likelihood of generating autoreactive T and B cells. The HLA class I and class II loci are the most polymorphic coding sequences in the human genome. Susceptibility and protection to a variety of diseases, many of which are common human disorders, are associated with specific alleles at HLA class I and class II loci and specific combinations of alleles, either in cis or in trans, determine the extent of genetic risk. Other loci within the MHC, as well as others scattered throughout the genome, are also likely to influence disease susceptibility and progression. Some of these loci have an apparent relevance to disease onset such as cytokine and cytokine receptor genes, whereas other more recently described genes have as yet unknown roles. Recent developments in the genetic analysis of autoimmune diseases are likely to have a significant clinical impact on the ability to predict disease predisposition as well as disease severity.