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Antony Rosen


February 27, 2014: This chapter has been re-evaluated and remains up-to-date. No changes have been necessary.

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date: 28 April 2017

Autoimmune diseases occur when a sustained, specific, adaptive immune response is generated against self-components, and results in tissue damage or dysfunction. They probably affect more than 3% of Western populations, more commonly women than men, and have peak incidence in the third to sixth decades.

Aetiology and pathogenesis

These can usefully be described in terms of (1) susceptibility—inherited or acquired defects in pathways required to maintain tolerance to self antigens render the individual susceptible to disease initiation; (2) initiation of autoimmunity—interaction between susceptibility genes and environmental events initiate an immune response directed at self antigens; (3) propagation—specific immune response to self antigens causes damage of tissues, with the release of more antigens that further drive the immune response; (4) transition—targets of immune response change and are amplified, with clinical symptoms assuming a recognizable phenotype.

Although a single immune effector pathway may predominate in generating tissue dysfunction and damage in some autoimmune diseases, it is much commoner for multiple effector pathways to participate in generating the final phenotype. Those pathways which generate tissue damage or dysfunction include autoantibody binding to target cells, immune complex-mediated activation of complement and Fc receptor (FcR) pathways, cytokine pathways, as well as lymphocyte-mediated cytotoxicity of target cells. The nature and sites of tissue damage determine the pathological and clinical features of specific diseases.

Tissue-specific autoimmune diseases

Immune-mediated damage is restricted to a particular tissue or organ that specifically expresses the targeted antigen, e.g. (1) Graves’ disease—autoantibodies bind to and stimulate the TSH receptor, resulting in thyrotoxicosis; (2) myasthenia gravis—autoantibodies target the acetylcholine receptor at the neuromuscular junction, resulting in muscular weakness and fatigue due to the inefficient transmission of the acetylcholine signal; (3) type 1 diabetes—a cytotoxic T-cell response to the β‎ cells of the pancreatic islets results in destruction of the insulin-producing cells.

Systemic autoimmune diseases

Typically characterized by simultaneous damage in multiple tissues, e.g. kidney, lung, skeletal muscle, nervous system, and skin. Unlike autoantibodies in tissue-specific autoimmune diseases, which target tissue-specific antigens, the autoantibodies in systemic autoimmune diseases are frequently directed against molecules expressed ubiquitously in multiple tissues, e.g. (1) aminoacyl-tRNA synthetases—targeted in autoimmune myositis and associated interstitial lung disease; (2) small nuclear ribonucleoproteins (snRNPs)—targeted in systemic lupus erythematosus (SLE); (3) toposiomerase-1—targeted in scleroderma. Each of these molecules is expressed in all cells, where they play critical roles in essential cellular processes, e.g. protein translation, mRNA splicing, and DNA replication and remodelling (respectively).

Nonsustained autoimmune diseases

Organ or tissue damage and dysfunction tend to be self-limited and resolve after the first attack, and are very unlikely to recur, e.g. epidemic Guillain–Barré syndrome. These diseases typically occur in the setting of infection, and are associated with cross-reactive antibody responses that recognize both components of the infecting organism as well as the target tissue.

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