Autoimmune Disease: Mechanisms

Abstract

The immune system provides protection against infections and repairs tissue damage induced by physical trauma. Autoimmune disease occurs when the immune response inadvertently inflicts damage to tissues in the body. Similar features between autoimmune diseases suggest that common pathogenic mechanisms could lead to the development of autoimmune disease in genetically susceptible individuals. Activation of specific innate immune pathways is a characteristic of many autoimmune diseases. Innate immune cell activation directs antigen‐specific autoimmune T and B cells to cause tissue pathology under the influence of sex hormones. Thus, most autoimmune diseases occur predominantly in one sex or the other such as type I diabetes, Crohn's disease and myocarditis in men vs. thyroiditis, rheumatoid arthritis and lupus in women. Importantly, at least 80% of all autoimmune diseases occur in women. Current research targets these common immune mechanisms in an effort to develop better therapies and to prevent autoimmune disease.

Key Concepts

  • Genes and the environment contribute to the development of autoimmune diseases.
  • Nearly 80% of autoimmune diseases occur in women.
  • Sex hormones regulate inflammation and alter autoimmune disease in animal models.
  • Estrogens increase auto‐antibodies, which are key diagnostic criteria for most autoimmune diseases.
  • Many theories exist for how infections and chemicals could cause autoimmune diseases.
  • Microbial and/or chemical activation of innate immunity must occur at the same time as damage to self‐tissues in order for autoimmune disease to develop.
  • Dysregulation of peripheral immunoregulatory mechanisms is a key characteristic of autoimmune diseases.
  • Successful treatment of autoimmune diseases might require the targeting of multiple effector pathways.

Keywords: genetics; epigenetics; environment; sex hormones; infection; innate immunity; tolerance

Figure 1. The development of autoimmune disease depends on a combination of genetic/epigenetic and environmental factors such as hormones, chemicals, diet, toxins, drugs and infections. Genetic pre‐disposition accounts for only about one‐third of the risk of developing an autoimmune disease, while non‐inherited environmental factors account for the remaining 70% risk.
Figure 2. Sex hormones influence the development of autoimmune disease. Estrogens, including estradiol (E2), stimulate antibody and auto‐antibody production from B cells, while androgens like testosterone (Te) amplify inflammation. At least 80% of the individuals with an autoimmune disease are women. Auto‐antibodies serve not only as key diagnostic and classification criteria for autoimmune diseases, but are involved in driving pathology by causing tissue damage.
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Further Reading

Fairweather D (2015) Autoimmune skin diseases: role of sex hormones, vitamin D and menopause. In: Farage MA , Miller KW , Fugate‐Woods N and Maibach HI (eds) Skin, Mucosa and Menopause: Management of Clinical Issues. Berlin Heidelberg: Springer‐Verlag.

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Rose NR and Mackay IR (eds) (2014) The Autoimmune Diseases, 5th edn. London: Elsevier Academic Press.

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Wahren‐Herlenius M and Dorner T (2013) Immunopathogenic mechanisms of systemic autoimmune disease. Lancet 382: 819–831.

Zouali M (ed) (2009) The Epigenetics of Autoimmune Diseases. Oxford: Wiley‐Blackwell.

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Fairweather, DeLisa, and Root‐Bernstein, Robert(Jul 2015) Autoimmune Disease: Mechanisms. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020193.pub2]