|Young woman with the typical "butterfly rash" found in systemic lupus erythematosus|
|Specialty||Rheumatology, immunology, gastroenterology, neurology, dermatology|
|Symptoms||Depends on the condition. Commonly low grade fever, feeling tired|
|Types||Alopecia areata, celiac disease, diabetes mellitus type 1, Graves' disease, inflammatory bowel disease, multiple sclerosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, others|
|Medication||Nonsteroidal anti-inflammatory drugs, immunosuppressants, intravenous immunoglobulin|
|Frequency||24 million / 7% (USA)|
An autoimmune disease is a condition arising from an abnormal immune response to a normal body part. There are at least 80 types of autoimmune diseases. Nearly any body part can be involved. Common symptoms include low grade fever and feeling tired. Often symptoms come and go.
The cause is generally unknown. Some autoimmune diseases such as lupus run in families, and certain cases may be triggered by infections or other environmental factors. Some common diseases that are generally considered autoimmune include celiac disease, diabetes mellitus type 1, Graves' disease, inflammatory bowel disease, multiple sclerosis, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus. The diagnosis can be difficult to determine.
Treatment depends on the type and severity of the condition. Nonsteroidal anti-inflammatory drugs (NSAIDs) and immunosuppressants are often used. Intravenous immunoglobulin may also occasionally be used. While treatment usually improves symptoms, they do not typically cure the disease.
About 24 million (7%) people in the United States are affected by an autoimmune disease. Women are more commonly affected than men. Often they start during adulthood. The first autoimmune diseases were described in the early 1900s.
Signs and symptoms
Autoimmune diseases have a wide variety of different effects. They do tend to have one of three characteristic pathological effects which characterize them as autoimmune diseases:
- Damage to or destruction of tissues
- Altered organ growth
- Altered organ function
It has been estimated that autoimmune diseases are among the leading causes of death among women in the United States in all age groups up to 65 years.
A substantial minority of the population suffers from these diseases, which are often chronic, debilitating, and life-threatening.
There are more than 80 illnesses caused by autoimmunity.
The cause is generally unknown. Some autoimmune diseases such as lupus run in families, and certain cases may be triggered by infections or other environmental factors. There are more than 100 autoimmune diseases. Some common diseases that are generally considered autoimmune include celiac disease, diabetes mellitus type 1, Graves' disease, inflammatory bowel disease, multiple sclerosis, psoriasis, rheumatoid arthritis, and systemic lupus erythematosus.
The human immune system typically produces both T cells and B cells that are capable of being reactive with self-antigens, but these self-reactive cells are usually either killed prior to becoming active within the immune system, placed into a state of anergy (silently removed from their role within the immune system due to over-activation), or removed from their role within the immune system by regulatory cells. When any one of these mechanisms fail, it is possible to have a reservoir of self-reactive cells that become functional within the immune system. The mechanisms of preventing self-reactive T cells from being created takes place through negative selection process within the thymus as the T cell is developing into a mature immune cell.
Some infections, such as Campylobacter jejuni, have antigens that are similar (but not identical) to our own self-molecules. In this case, a normal immune response to C. jejuni can result in the production of antibodies that also react to a lesser degree with gangliosides of myelin sheath surrounding peripheral nerves' axons (i.e., Guillain–Barré). A major understanding of the underlying pathophysiology of autoimmune diseases has been the application of genome wide association scans that have identified a degree of genetic sharing among the autoimmune diseases.
Autoimmunity, on the other hand, is the presence of self-reactive immune response (e.g., auto-antibodies, self-reactive T cells), with or without damage or pathology resulting from it. This may be restricted to certain organs (e.g. in autoimmune thyroiditis) or involve a particular tissue in different places (e.g. Goodpasture's disease which may affect the basement membrane in both the lung and the kidney).
There are many theories as to how an autoimmune disease state arises. Some common ones are listed below.
Cryptic determinants/molecular sequestration
Although it is possible for a potential autoantigen to be spatially sequestered in an immune privileged site within the body (e.g. the eye), mechanisms exist to express even these antigens in a tolerogenic fashion to the immune system. However, it is impossible to induce tolerance (immune unresponsiveness) to all aspects of an autoantigen. This is because under normal physiologic conditions some regions of a self-antigen are not expressed at a sufficient level to induce tolerance. These poorly displayed areas of an antigen are called "cryptic determinants." The immune system maintains a high-affinity repertoire to the cryptic self because the presentation of these determinants was insufficient to induce strong tolerance.
The concept of molecular mimicry describes a situation in which a foreign antigen can initiate an immune response in which a T or B cell component cross-recognizes self. The cross reactive immune response is responsible for the autoimmune disease state. Cross-reactive immune responses to self were first described for antibodies.
Altered glycan theory
According to this theory the effector function of the immune response is mediated by the glycans (polysaccharides) displayed by the cells and humoral components of the immune system. Individuals with autoimmunity have alterations in their glycosylation profile such that a proinflammatory immune response is favored. It is further hypothesized that individual autoimmune diseases will have unique glycan signatures.
According to the hygiene hypothesis, high levels of cleanliness expose children to fewer antigens than in the past, causing their immune systems to become overactive and more likely to misidentify own tissues as foreign, resulting in autoimmune or allergic conditions such as asthma.
- Direct evidence from transfer of disease-causing antibody or disease-causing T lymphocyte white blood cells
- Indirect evidence based on reproduction of the autoimmune disease in experimental animals
- Circumstantial evidence from clinical clues
The first estimate of US prevalence for autoimmune diseases as a group was published in 1997 by Jacobson, et al. They reported US prevalence to be around 9 million, applying prevalence estimates for 24 diseases to a US population of 279 million. Jacobson's work was updated by Hayter & Cook in 2012. This study used Witebsky's postulates, as revised by Rose & Bona, to extend the list to 81 diseases and estimated overall cumulative US prevalence for the 81 autoimmune diseases at 5.0%, with 3.0% for males and 7.1% for females. The estimated community prevalence, which takes into account the observation that many people have more than one autoimmune disease, was 4.5% overall, with 2.7% for males and 6.4% for females.
In both autoimmune and inflammatory diseases, the condition arises through aberrant reactions of the human adaptive or innate immune systems. In autoimmunity, the patient's immune system is activated against the body's own proteins. In chronic inflammatory diseases, neutrophils and other leukocytes are constitutively recruited by cytokines and chemokines, leading to tissue damage.
Mitigation of inflammation by activation of anti-inflammatory genes and the suppression of inflammatory genes in immune cells is a promising therapeutic approach. There is a body of evidence that once the production of autoantibodies has been initialized, autoantibodies have the capacity to maintain their own production.
Stem cell transplantation is being studied and has shown promising results in certain cases.
Traditionally it was believed that the immune system was unable to react against the body's own tissues, a concept described by the German immunologist Paul Ehrlich as "horror autotoxicus". In 1904 this theory was challenged by the discovery of a substance in the serum of patients with paroxysmal cold hemoglobinuria that reacted with red blood cells.
- "Autoimmune diseases fact sheet". OWH. 16 July 2012. Archived from the original on 5 October 2016. Retrieved 5 October 2016.
- Katz, U; Shoenfeld, Y; Zandman-Goddard, G (2011). "Update on intravenous immunoglobulins (IVIg) mechanisms of action and off- label use in autoimmune diseases". Current Pharmaceutical Design. 17 (29): 3166–75. doi:10.2174/138161211798157540. PMID 21864262.
- Borgelt, Laura Marie (2010). Women's Health Across the Lifespan: A Pharmacotherapeutic Approach. ASHP. p. 579. ISBN 9781585281947. Archived from the original on 2017-09-08.
- Hohlfeld, Reinhard; Dornmair, Klaus; Meinl, Edgar; Wekerle, Hartmut (2016). "The search for the target antigens of multiple sclerosis, part 1: Autoreactive CD4+ T lymphocytes as pathogenic effectors and therapeutic targets". The Lancet Neurology. 15 (2): 198–209. doi:10.1016/S1474-4422(15)00334-8. PMID 26724103.
- Paniker, Ananthanarayan And (2005). Ananthanarayan and Paniker's Textbook of Microbiology. Orient Blackswan. p. 169. ISBN 9788125028086. Archived from the original on 2017-09-08.
- "Autoimmune disorders: MedlinePlus Medical Encyclopedia". www.nlm.nih.gov. Archived from the original on 2016-01-12. Retrieved 2016-01-21.
- Walsh, SJ; Rau, LM (September 2000). "Autoimmune diseases: a leading cause of death among young and middle-aged women in the United States". American Journal of Public Health. 90 (9): 1463–6. doi:10.2105/ajph.90.9.1463. PMC 1447637. PMID 10983209.
- "MedlinePlus medical encyclopedia – autoimmune disorders". National Institutes of Health. 16 July 2014. Archived from the original on 5 January 2015. Retrieved 21 December 2014.
- "Autoimmune Disease List • AARDA". AARDA. 2016-06-01. Retrieved 2019-03-21.
- Cotsapas C, Hafler DA (2013). "Immune-mediated disease genetics: the shared basis of pathogenesis". Trends in Immunology. 34 (1): 22–6. doi:10.1016/j.it.2012.09.001. PMID 23031829.
- Harrison's Principles of Internal Medicine: Volumes 1 and 2, 18th Edition (18 ed.). McGraw-Hill Professional. 2011-08-11. ISBN 9780071748896.
- Gammon G, Sercarz E (1989). "How some T cells escape tolerance induction". Nature. 342 (6246): 183–5. Bibcode:1989Natur.342..183G. doi:10.1038/342183a0. PMID 2478888.
- Wucherpfennig KW, Strominger JL (1995). "Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein". Cell. 80 (5): 695–705. doi:10.1016/0092-8674(95)90348-8. PMID 7534214.
- Maverakis E, Kim K, Shimoda M, Gershwin M, Patel F, Wilken R, Raychaudhuri S, Ruhaak LR, Lebrilla CB (2015). "Glycans in the immune system and The Altered Glycan Theory of Autoimmunity". J Autoimmun. 57 (6): 1–13. doi:10.1016/j.jaut.2014.12.002. PMC 4340844. PMID 25578468.
- Rook, Graham A. W. (17 November 2011). "Hygiene Hypothesis and Autoimmune Diseases". Clinical Reviews in Allergy & Immunology. 42 (1): 5–15. doi:10.1007/s12016-011-8285-8. PMID 22090147.
- Witebsky E, Rose NR, Terplan K, Paine JR, Egan RW (1957). "Chronic thyroiditis and autoimmunization". J. Am. Med. Assoc. 164 (13): 1439–47. doi:10.1001/jama.1957.02980130015004. PMID 13448890.
- Rose NR, Bona C (September 1993). "Defining criteria for autoimmune diseases (Witebsky's postulates revisited)". Immunol. Today. 14 (9): 426–30. doi:10.1016/0167-5699(93)90244-F. PMID 8216719.
- Jacobson, DL; Gange, SJ; Rose, NR; Graham, NM (September 1997). "Epidemiology and estimated population burden of selected autoimmune diseases in the United States". Clinical Immunology and Immunopathology. 84 (3): 223–43. doi:10.1006/clin.1997.4412. PMID 9281381.
- Hayter, SM; Cook, MC (August 2012). "Updated assessment of the prevalence, spectrum and case definition of autoimmune disease". Autoimmunity Reviews. 11 (10): 754–65. doi:10.1016/j.autrev.2012.02.001. PMID 22387972.
- Rose, NR; Bona, C (September 1993). "Defining criteria for autoimmune diseases (Witebsky's postulates revisited)". Immunology Today. 14 (9): 426–30. doi:10.1016/0167-5699(93)90244-F. PMID 8216719.
- Mukundan L, Odegaard JI, Morel CR, Heredia JE, Mwangi JW, Ricardo-Gonzalez RR, Goh YP, Eagle AR, Dunn SE, et al. (Nov 2009). "PPAR-delta senses and orchestrates clearance of apoptotic cells to promote tolerance". Nat Med. 15 (11): 1266–72. doi:10.1038/nm.2048. PMC 2783696. PMID 19838202.
- Roszer T, Menéndez-Gutiérrez MP, Lefterova MI, Alameda D, Núñez V, Lazar MA, Fischer T, Ricote M (Jan 2011). "Autoimmune kidney disease and impaired engulfment of apoptotic cells in mice with macrophage peroxisome proliferator-activated receptor gamma or retinoid X receptor alpha deficiency". J Immunol. 186 (1): 621–31. doi:10.4049/jimmunol.1002230. PMC 4038038. PMID 21135166.
- Singh RP, Waldron RT, Hahn BH (2012). "Genes, tolerance and systemic autoimmunity". Autoimmunity Reviews. 11 (9): 664–9. doi:10.1016/j.autrev.2011.11.017. PMC 3306516. PMID 22155015.
- Böhm I (2003). "Disruption of the cytoskeleton after apoptosis induction by autoantibodies". Autoimmunity. 36 (3): 183–9. doi:10.1080/0891693031000105617. PMID 12911286.
- Swart, JF; Delemarre, EM; van Wijk, F; Boelens, JJ; Kuball, J; van Laar, JM; Wulffraat, NM (April 2017). "Haematopoietic stem cell transplantation for autoimmune diseases". Nature Reviews. Rheumatology. 13 (4): 244–256. doi:10.1038/nrrheum.2017.7. PMID 28228650.
- Moticka, Edward J. (2013). Historical perspective on evidence-based immunology. Elsevier Science Publishing. p. 300. ISBN 9780123983817.
- Vinay Kumar, Abul K. Abbas, Nelson Fausto, Jon Aster, Robbins and Cotran Pathologic Basis of Disease, Elsevier, 8th edition, 2010, 1464 pp., ISBN 978-1-4160-3121-5
- Handbook of Systemic Autoimmune Diseases, edited by Ronald Asherson, Elsevier, in 10 Volumes: http://www.elsevier.com/wps/find/bookdescription.cws_home/BS_HSAD/description#description