Autoimmunity
Encyclopedia
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease
. Autoimmunity is often caused by a lack of germ development of a target body and as such the immune response acts against its own cells and tissues. Prominent examples include Coeliac disease
, diabetes mellitus type 1
(IDDM), systemic lupus erythematosus
(SLE), Sjögren's syndrome
, Churg-Strauss Syndrome
, Hashimoto's thyroiditis
, Graves' disease
, idiopathic thrombocytopenic purpura
, rheumatoid arthritis
(RA), lupus
and allergies. Autoimmune diseases are very often treated with steroids.
The misconception that an individual's immune system is totally incapable of recognizing self antigens is not new. Paul Ehrlich
, at the beginning of the twentieth century, proposed the concept of horror autotoxicus, wherein a 'normal' body does not mount an immune response against its own tissues. Thus, any autoimmune response was perceived to be abnormal and postulated to be connected with human disease. Now, it is accepted that autoimmune responses are an integral part of vertebrate immune systems (sometimes termed 'natural autoimmunity'), normally prevented from causing disease by the phenomenon of immunological tolerance to self-antigens. Autoimmunity should not be confused with alloimmunity
.
.
Second, autoimmunity may have a role in allowing a rapid immune response in the early stages of an infection when the availability of foreign antigen
s limits the response (i.e., when there are few pathogens present). In their study, Stefanova et al. (2002) injected an anti-MHC Class II
antibody
into mice expressing a single type of MHC Class II molecule (H-2b) to temporarily prevent CD4+ T cell-MHC interaction. Naive
CD4+ T cells (those that have not encountered any antigens before) recovered from these mice 36 hours post-anti-MHC administration showed decreased responsiveness to the antigen
pigeon cytochrome C
peptide, as determined by Zap-70
phosphorylation
, proliferation, and Interleukin-2 production. Thus Stefanova et al. (2002) demonstrated that self-MHC recognition (which, if too strong may contribute to autoimmune disease) maintains the responsiveness of CD4+ T cells when foreign antigens are absent. This idea of autoimmunity is conceptually similar to play-fighting. The play-fighting of young cubs (TCR and self-MHC) may result in a few scratches or scars (low-level-autoimmunity), but is beneficial in the long-term as it primes the young cub for proper fights in the future.
in New York, and Roitt
and Doniach
at University College London
provided clear evidence that, at least in terms of antibody-producing B lymphocytes, diseases such as rheumatoid arthritis and thyrotoxicosis are associated with of loss of immunological tolerance, which is the ability of an individual to ignore 'self', while reacting to 'non-self'. This breakage leads to the immune system's mounting an effective and specific immune response against self determinants. The exact genesis of immunological tolerance is still elusive, but several theories have been proposed since the mid-twentieth century to explain its origin.
Three hypotheses have gained widespread attention among immunologists:
In addition, two other theories are under intense investigation:
Tolerance can also be differentiated into 'Central' and 'Peripheral' tolerance, on whether or not the above-stated checking mechanisms operate in the central lymphoid organs (Thymus and Bone Marrow) or the peripheral lymphoid organs (lymph node, spleen, etc., where self-reactive B-cells may be destroyed). It must be emphasised that these theories are not mutually exclusive, and evidence has been mounting suggesting that all of these mechanisms may actively contribute to vertebrate immunological tolerance.
A puzzling feature of the documented loss of tolerance seen in spontaneous human autoimmunity is that it is almost entirely restricted to the autoantibody responses produced by B lymphocytes. Loss of tolerance by T cells has been extremely hard to demonstrate, and where there is evidence for an abnormal T cell response it is usually not to the antigen recognised by autoantibodies. Thus, in rheumatoid arthritis there are autoantibodies to IgG Fc but apparently no corresponding T cell response. In systemic lupus there are autoantibodies to DNA, which cannot evoke a T cell response, and limited evidence for T cell responses implicates nucleoprotein antigens. In Celiac disease there are autoantibodies to tissue transglutaminase but the T cell response is to the foreign protein gliadin. This disparity has led to the idea that human autoimmune disease is in most cases (with probable exceptions including type I diabetes) based on a loss of B cell tolerance which makes use of normal T cell responses to foreign antigens in a variety of aberrant ways.
Three main sets of genes are suspected in many autoimmune diseases. These genes are related to:
The first two, which are involved in the recognition of antigens, are inherently variable and susceptible to recombination. These variations enable the immune system to respond to a very wide variety of invaders, but may also give rise to lymphocyte
s capable of self-reactivity.
Scientists such as H. McDevitt, G. Nepom, J. Bell and J. Todd have also provided strong evidence to suggest that certain MHC class II allotypes are strongly correlated with
Fewer correlations exist with MHC class I molecules. The most notable and consistent is the association between HLA B27 and ankylosing spondylitis
. Correlations may exist between polymorphisms
within class II MHC promoters and autoimmune disease.
The contributions of genes outside the MHC complex remain the subject of research, in animal models of disease (Linda Wicker's extensive genetic studies of diabetes in the NOD mouse), and in patients (Brian Kotzin's linkage analysis of susceptibility to SLE
).
Recently, PTPN22
has been associated with multiple autoimmune diseases including Type I diabetes, rheumatoid arthritis, systemic lupus erythematosis, Hashimoto’s thyroiditis, Graves’ disease, Addison’s disease, Myasthenia Gravis, vitiligo, systemic sclerosis juvenile idiopathic arthritis, and psoriatic arthritis.
A person's sex
also seems to have some role in the development of autoimmunity, classifying most autoimmune diseases as sex-related diseases. Nearly 75% of the more than 23.5 million Americans who suffer from autoimmune disease are women, although it is less-frequently acknowledged that millions of men also suffer from these diseases. According to the American Autoimmune Related Diseases Association (AARDA), autoimmune diseases that develop in men tend to be more severe. A few autoimmune diseases that men are just as or more likely to develop as women, include: ankylosing spondylitis
, type 1 diabetes mellitus, Wegener's granulomatosis
, Crohn's disease
and psoriasis
.
The reasons for the sex role in autoimmunity are unclear. Women appear to generally mount larger inflammatory responses than men when their immune systems are triggered, increasing the risk of autoimmunity. Involvement of sex steroids is indicated by that many autoimmune diseases tend to fluctuate in accordance with hormonal changes, for example, during pregnancy, in the menstrual cycle, or when using oral contraception. A history of pregnancy also appears to leave a persistent increased risk for autoimmune disease. It has been suggested that the slight exchange of cells between mothers and their children during pregnancy may induce autoimmunity. This would tip the gender balance in the direction of the female.
Another theory suggests the female high tendency to get autoimmunity is due to an imbalanced X chromosome inactivation. The X-inactivation skew theory, proposed by Princeton University's Jeff Stewart, has recently been confirmed experimentally in scleroderma and autoimmune thyroiditis. Other complex X-linked genetic susceptibility mechanisms are proposed and under investigation.
References to the original scientific literature would be helpful here.
attributes these correlations to the immune manipulating strategies of pathogens. Whilst such an observation has been variously termed as spurious and ineffective, according to some studies, parasite infection is associated with reduced activity of autoimmune disease.
The putative mechanism is that the parasite attenuates the host immune response in order to protect itself. This may provide a serendipitous benefit to a host that also suffers from autoimmune disease. The details of parasite immune modulation are not yet known, but may include secretion of anti-inflammatory agents or interference with the host immune signaling.
A paradoxical observation has been the strong association of certain microbial organisms with autoimmune diseases.
For example, Klebsiella pneumoniae
and coxsackievirus B
have been strongly correlated with ankylosing spondylitis
and diabetes mellitus type 1
, respectively. This has been explained by the tendency of the infecting organism to produce super-antigens that are capable of polyclonal activation of B-lymphocytes, and production of large amounts of antibodies of varying specificities, some of which may be self-reactive (see below).
Certain chemical agents and drugs can also be associated with the genesis of autoimmune conditions, or conditions that simulate autoimmune diseases. The most striking of these is the drug-induced lupus erythematosus
. Usually, withdrawal of the offending drug cures the symptoms in a patient.
Cigarette smoking is now established as a major risk factor for both incidence and severity of rheumatoid arthritis
. This may relate to abnormal citrullination
of proteins, since the effects of smoking correlate with the presence of antibodies to citrullinated peptides.
The roles of specialized immunoregulatory cell types, such as regulatory T cells, NKT cells
, γδ T-cells in the pathogenesis of autoimmune disease are under investigation.
Using the traditional “organ specific” and “non-organ specific” classification scheme, many diseases have been lumped together under the autoimmune disease umbrella. However, many chronic inflammatory human disorders lack the telltale associations of B and T cell driven immunopathology. In the last decade it has been firmly established that tissue "inflammation against self" does not necessarily rely on abnormal T and B cell responses.
This has led to the recent proposal that the spectrum of autoimmunity should be viewed along an “immunological disease continuum,” with classical autoimmune diseases at one extreme and diseases driven by the innate immune system at the other extreme. Within this scheme, the full spectrum of autoimmunity can be included. Many common human autoimmune diseases can be seen to have a substantial innate immune mediated immunopathology using this new scheme. This new classification scheme has implications for understanding disease mechanisms and for therapy development (see PLoS Medicine article. http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0030297).
). In several systemic disorders, serological assays which can detect specific autoantibodies can be employed. Localised disorders are best diagnosed by immunofluorescence
of biopsy specimens. Autoantibodies are used to diagnose many autoimmune diseases. The levels of autoantibodies are measured to determine the progress of the disease.
, anti-inflammatory
(steroids), or palliative. Non-immunological therapies, such as hormone replacement in Hashimoto's thyroiditis or Type 1 diabetes mellitus treat outcomes of the autoaggressive response, thus these are palliative treatments. Dietary manipulation limits the severity of celiac disease. Steroidal or NSAID treatment limits inflammatory symptoms of many diseases. IVIG is used for CIDP and GBS. Specific immunomodulator
y therapies, such as the TNFα antagonists (e.g. etanercept
), the B cell depleting agent rituximab
, the anti-IL-6 receptor tocilizumab
and the costimulation blocker abatacept
have been shown to be useful in treating RA. Some of these immunotherapies may be associated with increased risk of adverse effects, such as susceptibility to infection.
Helminthic therapy
is an experimental approach that involves inoculation of the patient with specific parasitic intestinal nematodes (helminths). There are currently two closely related treatments available, inoculation with either Necator americanus, commonly known as hookworm
s, or Trichuris Suis Ova, commonly known as Pig Whipworm Eggs.
T cell vaccination
is also being explored as a possible future therapy for auto-immune disorders.
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
. Autoimmunity is often caused by a lack of germ development of a target body and as such the immune response acts against its own cells and tissues. Prominent examples include Coeliac disease
Coeliac disease
Coeliac disease , is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward...
, diabetes mellitus type 1
Insulin-dependent diabetes mellitus
Insulin-dependent diabetes mellitus is a medical term that describes diabetes mellitus that requires insulin therapy to avoid ketoacidosis...
(IDDM), systemic lupus erythematosus
Lupus erythematosus
Lupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...
(SLE), Sjögren's syndrome
Sjögren's syndrome
Sjögren's syndrome , also known as "Mikulicz disease" and "Sicca syndrome", is a systemic autoimmune disease in which immune cells attack and destroy the exocrine glands that produce tears and saliva....
, Churg-Strauss Syndrome
Churg-Strauss syndrome
Churg–Strauss syndrome is a medium and small vessel autoimmune vasculitis, leading to necrosis. It involves mainly the blood vessels of the lungs , gastrointestinal system, and peripheral nerves, but also affects the heart, skin and kidneys. It is a rare disease that is non-inheritable and...
, Hashimoto's thyroiditis
Hashimoto's thyroiditis
Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease...
, Graves' disease
Graves' disease
Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones...
, idiopathic thrombocytopenic purpura
Idiopathic thrombocytopenic purpura
Idiopathic thrombocytopenic purpura is the condition of having an abnormally low platelet count of no known cause . As most incidents of ITP appear to be related to the production of antibodies against platelets, immune thrombocytopenic purpura or immune thrombocytopenia are terms also used to...
, rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
(RA), lupus
Lupus
Lupus most commonly refers to the disease systemic lupus erythematosus.Lupus may also refer to:-Medicine:* Lupus erythematosus, a chronic autoimmune disease with several different forms...
and allergies. Autoimmune diseases are very often treated with steroids.
The misconception that an individual's immune system is totally incapable of recognizing self antigens is not new. Paul Ehrlich
Paul Ehrlich
Paul Ehrlich was a German scientist in the fields of hematology, immunology, and chemotherapy, and Nobel laureate. He is noted for curing syphilis and for his research in autoimmunity, calling it "horror autotoxicus"...
, at the beginning of the twentieth century, proposed the concept of horror autotoxicus, wherein a 'normal' body does not mount an immune response against its own tissues. Thus, any autoimmune response was perceived to be abnormal and postulated to be connected with human disease. Now, it is accepted that autoimmune responses are an integral part of vertebrate immune systems (sometimes termed 'natural autoimmunity'), normally prevented from causing disease by the phenomenon of immunological tolerance to self-antigens. Autoimmunity should not be confused with alloimmunity
Alloimmunity
Alloimmunity is a condition in which the body gains immunity against antigens of another individual of the same species, which are perceived as foreign....
.
Low-level autoimmunity
While a high level of autoimmunity is unhealthy, a low level of autoimmunity may actually be beneficial. First, low-level autoimmunity might aid in the recognition of neoplastic cells by CD8+ T cells, and thus reduce the incidence of cancerCancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
.
Second, autoimmunity may have a role in allowing a rapid immune response in the early stages of an infection when the availability of foreign antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s limits the response (i.e., when there are few pathogens present). In their study, Stefanova et al. (2002) injected an anti-MHC Class II
MHC class II
MHC Class II molecules are found only on a few specialized cell types, including macrophages, dendritic cells and B cells, all of which are professional antigen-presenting cells ....
antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
into mice expressing a single type of MHC Class II molecule (H-2b) to temporarily prevent CD4+ T cell-MHC interaction. Naive
Drug-naïve
Drug-naïve is the term used to describe patients or animals who are not under the influence of any psychotropic substances . This term usually refers to patients or animals undergoing drug-related testing, such as the effect of a certain drug on behaviour or cognitive ability.More specifically, it...
CD4+ T cells (those that have not encountered any antigens before) recovered from these mice 36 hours post-anti-MHC administration showed decreased responsiveness to the antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
pigeon cytochrome C
Cytochrome c
The Cytochrome complex, or cyt c is a small heme protein found loosely associated with the inner membrane of the mitochondrion. It belongs to the cytochrome c family of proteins. Cytochrome c is a highly soluble protein, unlike other cytochromes, with a solubility of about 100 g/L and is an...
peptide, as determined by Zap-70
ZAP-70
ZAP-70 is an abbreviation for Zeta-chain-associated protein kinase 70 . The protein is a member in the protein-tyrosine kinase family...
phosphorylation
Phosphorylation
Phosphorylation is the addition of a phosphate group to a protein or other organic molecule. Phosphorylation activates or deactivates many protein enzymes....
, proliferation, and Interleukin-2 production. Thus Stefanova et al. (2002) demonstrated that self-MHC recognition (which, if too strong may contribute to autoimmune disease) maintains the responsiveness of CD4+ T cells when foreign antigens are absent. This idea of autoimmunity is conceptually similar to play-fighting. The play-fighting of young cubs (TCR and self-MHC) may result in a few scratches or scars (low-level-autoimmunity), but is beneficial in the long-term as it primes the young cub for proper fights in the future.
Immunological tolerance
Pioneering work by Noel Rose and WitebskyErnst Witebsky
Ernst Witebsky, also Ernest Witebsky was a German-American immunologist.From 1920 to 1926 Witebsky studied medicine at the University of Frankfurt and the University of Heidelberg. He stayed at Heidelberg after graduating and worked with Dr. Hans Sachs...
in New York, and Roitt
Ivan Roitt
Professor Ivan Maurice Roitt was educated at King Edward's School, Birmingham and Balliol College, Oxford University.In 1956, together with Deborah Doniach and Peter Campbell, he made the classic discovery of thyroglobulin autoantibodies in Hashimoto's thyroiditis which helped to open the whole...
and Doniach
Deborah Doniach
Professor Deborah Doniach, MD, FRCP was a distinguished clinical immunologist and pioneer in the field of autoimmune diseases. -Selected Published Works:...
at University College London
University College London
University College London is a public research university located in London, United Kingdom and the oldest and largest constituent college of the federal University of London...
provided clear evidence that, at least in terms of antibody-producing B lymphocytes, diseases such as rheumatoid arthritis and thyrotoxicosis are associated with of loss of immunological tolerance, which is the ability of an individual to ignore 'self', while reacting to 'non-self'. This breakage leads to the immune system's mounting an effective and specific immune response against self determinants. The exact genesis of immunological tolerance is still elusive, but several theories have been proposed since the mid-twentieth century to explain its origin.
Three hypotheses have gained widespread attention among immunologists:
- Clonal Deletion theory, proposed by BurnetFrank Macfarlane BurnetSir Frank Macfarlane Burnet, , usually known as Macfarlane or Mac Burnet, was an Australian virologist best known for his contributions to immunology....
, according to which self-reactive lymphoid cells are destroyed during the development of the immune system in an individual. For their work Frank M. Burnet and Peter B. Medawar were awarded the 1960 Nobel Prize in Physiology or Medicine "for discovery of acquired immunological tolerance". - Clonal Anergy theory, proposed by NossalGustav NossalSir Gustav Victor Joseph Nossal, AC, CBE, FRS, FAA is an Australian research biologist.-Life and career:Gustav Nossal's family was from Vienna, Austria. He was born four weeks prematurely in Bad Ischl while his mother was on holiday...
, in which self-reactive T- or B-cells become inactivated in the normal individual and cannot amplify the immune response. - Idiotype Network theory, proposed by Jerne, wherein a network of antibodies capable of neutralizing self-reactive antibodies exists naturally within the body.
In addition, two other theories are under intense investigation:
- The so-called "Clonal Ignorance" theory, according to which host immune responses are directed to ignore self-antigens
- The "Suppressor population" or "Regulatory T cellRegulatory T cellRegulatory T cells , sometimes known as suppressor T cells, are a specialized subpopulation of T cells which suppresses activation of the immune system and thereby maintains tolerance to self-antigens. The existence of regulatory T cells was the subject of significant controversy among...
" theories, wherein regulatory T-lymphocytes (commonly CD4+FoxP3+ cells, among others) function to prevent, downregulate, or limit autoaggressive immune responses in the immune system.
Tolerance can also be differentiated into 'Central' and 'Peripheral' tolerance, on whether or not the above-stated checking mechanisms operate in the central lymphoid organs (Thymus and Bone Marrow) or the peripheral lymphoid organs (lymph node, spleen, etc., where self-reactive B-cells may be destroyed). It must be emphasised that these theories are not mutually exclusive, and evidence has been mounting suggesting that all of these mechanisms may actively contribute to vertebrate immunological tolerance.
A puzzling feature of the documented loss of tolerance seen in spontaneous human autoimmunity is that it is almost entirely restricted to the autoantibody responses produced by B lymphocytes. Loss of tolerance by T cells has been extremely hard to demonstrate, and where there is evidence for an abnormal T cell response it is usually not to the antigen recognised by autoantibodies. Thus, in rheumatoid arthritis there are autoantibodies to IgG Fc but apparently no corresponding T cell response. In systemic lupus there are autoantibodies to DNA, which cannot evoke a T cell response, and limited evidence for T cell responses implicates nucleoprotein antigens. In Celiac disease there are autoantibodies to tissue transglutaminase but the T cell response is to the foreign protein gliadin. This disparity has led to the idea that human autoimmune disease is in most cases (with probable exceptions including type I diabetes) based on a loss of B cell tolerance which makes use of normal T cell responses to foreign antigens in a variety of aberrant ways.
Genetic Factors
Certain individuals are genetically susceptible to developing autoimmune diseases. This susceptibility is associated with multiple genes plus other risk factors. Genetically predisposed individuals do not always develop autoimmune diseases.Three main sets of genes are suspected in many autoimmune diseases. These genes are related to:
- Immunoglobulins
- T-cell receptors
- The major histocompatibility complexMajor histocompatibility complexMajor histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
es (MHC).
The first two, which are involved in the recognition of antigens, are inherently variable and susceptible to recombination. These variations enable the immune system to respond to a very wide variety of invaders, but may also give rise to lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s capable of self-reactivity.
Scientists such as H. McDevitt, G. Nepom, J. Bell and J. Todd have also provided strong evidence to suggest that certain MHC class II allotypes are strongly correlated with
- HLA DR2 is strongly positively correlated with Systemic Lupus ErythematosusSystemic lupus erythematosusSystemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
, narcolepsyNarcolepsyNarcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
and multiple sclerosisMultiple sclerosisMultiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
, and negatively correlated with DM Type 1. - HLA DR3 is correlated strongly with Sjögren's syndromeSjögren's syndromeSjögren's syndrome , also known as "Mikulicz disease" and "Sicca syndrome", is a systemic autoimmune disease in which immune cells attack and destroy the exocrine glands that produce tears and saliva....
, myasthenia gravisMyasthenia gravisMyasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...
, SLELupus erythematosusLupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...
, and DM Type 1. - HLA DR4 is correlated with the genesis of rheumatoid arthritisRheumatoid arthritisRheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
, Type 1 diabetes mellitusDiabetes mellitusDiabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
, and pemphigus vulgarisPemphigus vulgarisPemphigus vulgaris is a chronic blistering skin disease with skin lesions that are rarely pruritic, but which are often painful.-Pathophysiology:...
.
Fewer correlations exist with MHC class I molecules. The most notable and consistent is the association between HLA B27 and ankylosing spondylitis
Ankylosing spondylitis
Ankylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...
. Correlations may exist between polymorphisms
Polymorphism (biology)
Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...
within class II MHC promoters and autoimmune disease.
The contributions of genes outside the MHC complex remain the subject of research, in animal models of disease (Linda Wicker's extensive genetic studies of diabetes in the NOD mouse), and in patients (Brian Kotzin's linkage analysis of susceptibility to SLE
Lupus erythematosus
Lupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...
).
Recently, PTPN22
PTPN22
Protein tyrosine phosphatase, non-receptor type 22 , also known as PTPN22, is a protein that in humans is encoded by the PTPN22 gene. Alternative splicing of this gene results in two transcript variants encoding distinct isoforms...
has been associated with multiple autoimmune diseases including Type I diabetes, rheumatoid arthritis, systemic lupus erythematosis, Hashimoto’s thyroiditis, Graves’ disease, Addison’s disease, Myasthenia Gravis, vitiligo, systemic sclerosis juvenile idiopathic arthritis, and psoriatic arthritis.
Sex
| Ratio of female/male incidence Incidence (epidemiology) Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the... of autoimmune diseases |
|
|---|---|
| Hashimoto's thyroiditis Hashimoto's thyroiditis Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease... |
10/1 |
| Graves' disease Graves' disease Graves' disease is an autoimmune disease where the thyroid is overactive, producing an excessive amount of thyroid hormones... |
7/1 |
| Multiple sclerosis Multiple sclerosis Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms... (MS) |
2/1 |
| Myasthenia gravis Myasthenia gravis Myasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability... |
2/1 |
| Systemic lupus erythematosus Systemic lupus erythematosus Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage... (SLE) |
9/1 |
| Rheumatoid arthritis Rheumatoid arthritis Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development... |
5/2 |
A person's sex
Sex
In biology, sex is a process of combining and mixing genetic traits, often resulting in the specialization of organisms into a male or female variety . Sexual reproduction involves combining specialized cells to form offspring that inherit traits from both parents...
also seems to have some role in the development of autoimmunity, classifying most autoimmune diseases as sex-related diseases. Nearly 75% of the more than 23.5 million Americans who suffer from autoimmune disease are women, although it is less-frequently acknowledged that millions of men also suffer from these diseases. According to the American Autoimmune Related Diseases Association (AARDA), autoimmune diseases that develop in men tend to be more severe. A few autoimmune diseases that men are just as or more likely to develop as women, include: ankylosing spondylitis
Ankylosing spondylitis
Ankylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...
, type 1 diabetes mellitus, Wegener's granulomatosis
Wegener's granulomatosis
Wegener's granulomatosis , more recently granulomatosis with polyangiitis , is an incurable form of vasculitis that affects the nose, lungs, kidneys and other organs. Due to its end-organ damage, it is life-threatening and requires long-term immunosuppression...
, Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
and psoriasis
Psoriasis
Psoriasis is an autoimmune disease that appears on the skin. It occurs when the immune system mistakes the skin cells as a pathogen, and sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is not contagious. However, psoriasis has been linked to an increased risk of...
.
The reasons for the sex role in autoimmunity are unclear. Women appear to generally mount larger inflammatory responses than men when their immune systems are triggered, increasing the risk of autoimmunity. Involvement of sex steroids is indicated by that many autoimmune diseases tend to fluctuate in accordance with hormonal changes, for example, during pregnancy, in the menstrual cycle, or when using oral contraception. A history of pregnancy also appears to leave a persistent increased risk for autoimmune disease. It has been suggested that the slight exchange of cells between mothers and their children during pregnancy may induce autoimmunity. This would tip the gender balance in the direction of the female.
Another theory suggests the female high tendency to get autoimmunity is due to an imbalanced X chromosome inactivation. The X-inactivation skew theory, proposed by Princeton University's Jeff Stewart, has recently been confirmed experimentally in scleroderma and autoimmune thyroiditis. Other complex X-linked genetic susceptibility mechanisms are proposed and under investigation.
References to the original scientific literature would be helpful here.
Environmental Factors
An interesting inverse relationship exists between infectious diseases and autoimmune diseases. In areas where multiple infectious diseases are endemic, autoimmune diseases are quite rarely seen. The reverse, to some extent, seems to hold true. The hygiene hypothesisHygiene hypothesis
In medicine, the Hygiene Hypothesis states that a lack of early childhood exposure to infectious agents, symbiotic microorganisms , and parasites increases susceptibility to allergic diseases by suppressing natural development of the immune system...
attributes these correlations to the immune manipulating strategies of pathogens. Whilst such an observation has been variously termed as spurious and ineffective, according to some studies, parasite infection is associated with reduced activity of autoimmune disease.
The putative mechanism is that the parasite attenuates the host immune response in order to protect itself. This may provide a serendipitous benefit to a host that also suffers from autoimmune disease. The details of parasite immune modulation are not yet known, but may include secretion of anti-inflammatory agents or interference with the host immune signaling.
A paradoxical observation has been the strong association of certain microbial organisms with autoimmune diseases.
For example, Klebsiella pneumoniae
Klebsiella pneumoniae
Klebsiella pneumoniae is a Gram-negative, non-motile, encapsulated, lactose fermenting, facultative anaerobic, rod shaped bacterium found in the normal flora of the mouth, skin, and intestines....
and coxsackievirus B
Coxsackie B
Coxsackie B is the name of a group of six serotypes of pathogenic enteroviruses that trigger illness ranging from mild gastrointestinal distress to full-fledged pericarditis and myocarditis.-Geographic distribution:...
have been strongly correlated with ankylosing spondylitis
Ankylosing spondylitis
Ankylosing spondylitis , previously known as Bekhterev's disease, Bekhterev syndrome, and Marie-Strümpell disease is a chronic inflammatory disease of the axial skeleton with variable involvement of peripheral joints and nonarticular structures...
and diabetes mellitus type 1
Diabetes mellitus type 1
Diabetes mellitus type 1 is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose...
, respectively. This has been explained by the tendency of the infecting organism to produce super-antigens that are capable of polyclonal activation of B-lymphocytes, and production of large amounts of antibodies of varying specificities, some of which may be self-reactive (see below).
Certain chemical agents and drugs can also be associated with the genesis of autoimmune conditions, or conditions that simulate autoimmune diseases. The most striking of these is the drug-induced lupus erythematosus
Drug-induced lupus erythematosus
Drug-induced lupus erythematosus is an autoimmune disorder caused by chronic use of certain drugs. These drugs cause an autoimmune response producing symptoms similar to those of SLE...
. Usually, withdrawal of the offending drug cures the symptoms in a patient.
Cigarette smoking is now established as a major risk factor for both incidence and severity of rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
. This may relate to abnormal citrullination
Citrullination
Citrullination or deimination is the term used for the post-translational modification of the amino acid arginine in a protein into the amino acid citrulline. This reaction, shown below, is performed by enzymes called peptidylarginine deiminases...
of proteins, since the effects of smoking correlate with the presence of antibodies to citrullinated peptides.
Pathogenesis of autoimmunity
Several mechanisms are thought to be operative in the pathogenesis of autoimmune diseases, against a backdrop of genetic predisposition and environmental modulation. It is beyond the scope of this article to discuss each of these mechanisms exhaustively, but a summary of some of the important mechanisms have been described:- T-Cell Bypass - A normal immune system requires the activation of B-cells by T-cells before the former can produce antibodies in large quantities. This requirement of a T-cell can be bypassed in rare instances, such as infection by organisms producing super-antigens, which are capable of initiating polyclonal activation of B-cells, or even of T-cells, by directly binding to the β-subunit of T-cell receptors in a non-specific fashion.
- T-Cell-B-Cell discordance - A normal immune response is assumed to involve B and T cell responses to the same antigen, even if we know that B cells and T cells recognise very different things: conformations on the surface of a molecule for B cells and pre-processed peptide fragments of proteins for T cells. However, there is nothing as far as we know that requires this. All that is required is that a B cell recognising antigen X endocytoses and processes a protein Y (normally =X) and presents it to a T cell. Roosnek and Lanzavecchia showed that B cells recognising IgGFc could get help from any T cell responding to an antigen co-endocytosed with IgG by the B cell as part of an immune complex. In coeliac disease it seems likely that B cells recognising tissue transglutamine are helped by T cells recognising gliadin.
- Aberrant B cell receptor-mediated feedback - A feature of human autoimmune disease is that it is largely restricted to a small group of antigens, several of which have known signaling roles in the immune response (DNA, C1q, IgGFc, Ro, Con. A receptor, Peanut agglutinin receptor(PNAR)). This fact gave rise to the idea that spontaneous autoimmunity may result when the binding of antibody to certain antigens leads to aberrant signals being fed back to parent B cells through membrane bound ligands. These ligands include B cell receptor (for antigen), IgG Fc receptors, CD21, which binds complement C3d, Toll-like receptors 9 and 7 (which can bind DNA and nucleoproteins) and PNAR. More indirect aberrant activation of B cells can also be envisaged with autoantibodies to acetyl choline receptor (on thymic myoid cells) and hormone and hormone binding proteins. Together with the concept of T-cell-B-cell discordance this idea forms the basis of the hypothesis of self-perpetuating autoreactive B cells. Autoreactive B cells in spontaneous autoimmunity are seen as surviving because of subversion both of the T cell help pathway and of the feedback signal through B cell receptor, thereby overcoming the negative signals responsible for B cell self-tolerance without necessarily requiring loss of T cell self-tolerance.
- Molecular MimicryMolecular mimicryMolecular mimicry is defined as the theoretical possibility that sequence similarities between foreign and self-peptides are sufficient to result in the cross-activation of autoreactive T or B cells by pathogen-derived peptides...
- An exogenous antigenAntigenAn antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
may share structural similarities with certain host antigens; thus, any antibody produced against this antigen (which mimics the self-antigens) can also, in theory, bind to the host antigens, and amplify the immune response. The idea of molecular mimicry arose in the context of Rheumatic FeverRheumatic feverRheumatic fever is an inflammatory disease that occurs following a Streptococcus pyogenes infection, such as strep throat or scarlet fever. Believed to be caused by antibody cross-reactivity that can involve the heart, joints, skin, and brain, the illness typically develops two to three weeks after...
, which follows infection with Group A beta-haemolytic streptococci. Although rheumatic fever has been attributed to molecular mimicry for half a century no antigen has been formally identified (if anything too many have been proposed). Moreover, the complex tissue distribution of the disease (heart, joint, skin, basal ganglia) argues against a cardiac specific antigen. It remains entirely possible that the disease is due to e.g. an unusual interaction between immune complexes, complement components and endothelium. - Idiotype Cross-Reaction - Idiotypes are antigenic epitopes found in the antigen-binding portion (Fab) of the immunoglobulin molecule. Plotz and Oldstone presented evidence that autoimmunity can arise as a result of a cross-reaction between the idiotype on an antiviral antibody and a host cell receptor for the virus in question. In this case, the host-cell receptor is envisioned as an internal image of the virus, and the anti-idiotype antibodies can react with the host cells.
- Cytokine Dysregulation - Cytokines have been recently divided into two groups according to the population of cells whose functions they promote: Helper T-cells type 1 or type 2. The second category of cytokines, which include IL-4, IL-10 and TGF-β (to name a few), seem to have a role in prevention of exaggeration of pro-inflammatory immune responses.
- Dendritic cell apoptosis - immune system cells called dendritic cellDendritic cellDendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...
s present antigenAntigenAn antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s to active lymphocytes. Dendritic cells that are defective in apoptosis can lead to inappropriate systemic lymphocyteLymphocyteA lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
activation and consequent decline in self-tolerance. - Epitope spreading or epitope drift - when the immune reaction changes from targeting the primary epitopeEpitopeAn epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that recognizes the epitope is called a paratope...
to also targeting other epitopes. In contrast to molecular mimicry, the other epitopes need not be structurally similar to the primary one. - Epitope modification or Cryptic epitope exposure – this mechanism of autoimmune disease is unique in that it does not result from a defect in the hematopoietic system. Instead, disease results from the exposure of cryptic N-glycan (polysaccharide) linkages common to lower eukaryotes and prokaryotes on the glycoproteins of mammalian non-hematopoietic cells and organs This exposure of phylogenically primitive glycans activates one or more mammalian innate immune cell receptors to induce a chronic sterile inflammatory state. In the presence of chronic and inflammatory cell damage, the adaptive immune system is recruited and self–tolerance is lost with increased autoantibody production. In this form of the disease, the absence of lymphocytes can accelerate organ damage, and intravenous IgG administration can be therapeutic. Although this route to autoimmune disease may underlie various degenerative disease states, no diagnostics for this disease mechanism exist at present, and thus its role in human autoimmunity is currently unknown.
The roles of specialized immunoregulatory cell types, such as regulatory T cells, NKT cells
Natural Killer T cell
Natural killer T cells are a heterogeneous group of T cells that share properties of both T cells and natural killer cells. Many of these cells recognize the non-polymorphic CD1d molecule, an antigen-presenting molecule that binds self- and foreign lipids and glycolipids...
, γδ T-cells in the pathogenesis of autoimmune disease are under investigation.
Classification
Autoimmune diseases can be broadly divided into systemic and organ-specific or localised autoimmune disorders, depending on the principal clinico-pathologic features of each disease.- Systemic autoimmune diseases include SLELupus erythematosusLupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...
, Sjögren's syndromeSjögren's syndromeSjögren's syndrome , also known as "Mikulicz disease" and "Sicca syndrome", is a systemic autoimmune disease in which immune cells attack and destroy the exocrine glands that produce tears and saliva....
, sclerodermaSclerodermaSystemic sclerosis or systemic scleroderma is a systemic autoimmune disease or systemic connective tissue disease that is a subtype of scleroderma.-Skin symptoms:...
, rheumatoid arthritisRheumatoid arthritisRheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...
, and dermatomyositisDermatomyositisDermatomyositis is a connective-tissue disease related to polymyositis and Bramaticosis that is characterized by inflammation of the muscles and the skin.- Causes :...
. These conditions tend to be associated with autoantibodies to antigens which are not tissue specific. Thus although polymyositisPolymyositisPolymyositis is a type of chronic inflammation of the muscles related to dermatomyositis and inclusion body myositis.-Signs and symptoms:...
is more or less tissue specific in presentation, it may be included in this group because the autoantigens are often ubiquitous t-RNA synthetases.
- Local syndromes which affect a specific organ or tissue:
- Endocrinologic: Diabetes mellitus type 1Diabetes mellitus type 1Diabetes mellitus type 1 is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose...
, Hashimoto's thyroiditisHashimoto's thyroiditisHashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease...
, Addison's diseaseAddison's diseaseAddison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones... - Gastrointestinal: Coeliac diseaseCoeliac diseaseCoeliac disease , is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward...
, Crohn's DiseaseCrohn's diseaseCrohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
, Pernicious anaemia - Dermatologic: Pemphigus vulgarisPemphigus vulgarisPemphigus vulgaris is a chronic blistering skin disease with skin lesions that are rarely pruritic, but which are often painful.-Pathophysiology:...
, VitiligoVitiligoVitiligo is a condition that causes depigmentation of sections of skin. It occurs when melanocytes, the cells responsible for skin pigmentation, die or are unable to function. The cause of vitiligo is unknown, but research suggests that it may arise from autoimmune, genetic, oxidative stress,... - Haematologic: Autoimmune haemolytic anaemia, Idiopathic thrombocytopenic purpuraIdiopathic thrombocytopenic purpuraIdiopathic thrombocytopenic purpura is the condition of having an abnormally low platelet count of no known cause . As most incidents of ITP appear to be related to the production of antibodies against platelets, immune thrombocytopenic purpura or immune thrombocytopenia are terms also used to...
- Neurological: Myasthenia gravisMyasthenia gravisMyasthenia gravis is an autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatiguability...
- Endocrinologic: Diabetes mellitus type 1
Using the traditional “organ specific” and “non-organ specific” classification scheme, many diseases have been lumped together under the autoimmune disease umbrella. However, many chronic inflammatory human disorders lack the telltale associations of B and T cell driven immunopathology. In the last decade it has been firmly established that tissue "inflammation against self" does not necessarily rely on abnormal T and B cell responses.
This has led to the recent proposal that the spectrum of autoimmunity should be viewed along an “immunological disease continuum,” with classical autoimmune diseases at one extreme and diseases driven by the innate immune system at the other extreme. Within this scheme, the full spectrum of autoimmunity can be included. Many common human autoimmune diseases can be seen to have a substantial innate immune mediated immunopathology using this new scheme. This new classification scheme has implications for understanding disease mechanisms and for therapy development (see PLoS Medicine article. http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0030297).
Diagnosis
Diagnosis of autoimmune disorders largely rests on accurate history and physical examination of the patient, and high index of suspicion against a backdrop of certain abnormalities in routine laboratory tests (example, elevated C-reactive proteinC-reactive protein
C-reactive protein is a protein found in the blood, the levels of which rise in response to inflammation...
). In several systemic disorders, serological assays which can detect specific autoantibodies can be employed. Localised disorders are best diagnosed by immunofluorescence
Immunofluorescence
Immunofluorescence is a technique used for light microscopy with a fluorescence microscope and is used primarily on biological samples. This technique uses the specificity of antibodies to their antigen to target fluorescent dyes to specific biomolecule targets within a cell, and therefore allows...
of biopsy specimens. Autoantibodies are used to diagnose many autoimmune diseases. The levels of autoantibodies are measured to determine the progress of the disease.
Treatments
Treatments for autoimmune disease have traditionally been immunosuppressiveImmunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
, anti-inflammatory
Anti-inflammatory
Anti-inflammatory refers to the property of a substance or treatment that reduces inflammation. Anti-inflammatory drugs make up about half of analgesics, remedying pain by reducing inflammation as opposed to opioids, which affect the central nervous system....
(steroids), or palliative. Non-immunological therapies, such as hormone replacement in Hashimoto's thyroiditis or Type 1 diabetes mellitus treat outcomes of the autoaggressive response, thus these are palliative treatments. Dietary manipulation limits the severity of celiac disease. Steroidal or NSAID treatment limits inflammatory symptoms of many diseases. IVIG is used for CIDP and GBS. Specific immunomodulator
Immunomodulator
An immunomodulator, also known as an immunotherapy is a substance which has an effect on the immune system.- Immunosuppressants :Inhibits immune response in organ transplantation and autoimmune diseases.- Immunostimulants :...
y therapies, such as the TNFα antagonists (e.g. etanercept
Etanercept
Etanercept is a drug that treats autoimmune diseases by interfering with the tumor necrosis factor by acting as a TNF inhibitor. Pfizer describes in a SEC filing that the drug is used to treat rheumatoid, juvenile rheumatoid and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis...
), the B cell depleting agent rituximab
Rituximab
Rituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
, the anti-IL-6 receptor tocilizumab
Tocilizumab
Tocilizumab is an immunosuppressive drug, mainly for the treatment of rheumatoid arthritis and systemic juvenile idiopathic arthritis, a severe form of RA in children. It is a humanized monoclonal antibody against the interleukin-6 receptor...
and the costimulation blocker abatacept
Abatacept
Abatacept is a fusion protein composed of an immunoglobulin fused to the extracellular domain of CTLA-4, a molecule capable of binding B7. Abatacept is a selective costimulation modulator as it inhibits the costimulation of T cells...
have been shown to be useful in treating RA. Some of these immunotherapies may be associated with increased risk of adverse effects, such as susceptibility to infection.
Helminthic therapy
Helminthic therapy
Helminthic therapy, a type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the ova of a helminth. Helminths are parasitic worms such as hookworms and whipworms....
is an experimental approach that involves inoculation of the patient with specific parasitic intestinal nematodes (helminths). There are currently two closely related treatments available, inoculation with either Necator americanus, commonly known as hookworm
Hookworm
The hookworm is a parasitic nematode that lives in the small intestine of its host, which may be a mammal such as a dog, cat, or human. Two species of hookworms commonly infect humans, Ancylostoma duodenale and Necator americanus. A. duodenale predominates in the Middle East, North Africa, India...
s, or Trichuris Suis Ova, commonly known as Pig Whipworm Eggs.
T cell vaccination
T cell vaccination
T cell vaccination is immunization with inactivated autoreactive T cells. The concept of T cell vaccination is, at least partially, analogous to classical vaccination against infectious disease. However, the agents to be eliminated or neutralized are not foreign microbial agents but a pathogenic...
is also being explored as a possible future therapy for auto-immune disorders.
See also
- Autoimmune diseaseAutoimmune diseaseAutoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
- Protective autoimmunityProtective autoimmunityProtective autoimmunity is a condition in which cells of the adaptive immune system contribute to maintenance of the functional integrity of a tissue, or facilitate its repair following an insult. The term ‘protective autoimmunity’ was coined by Prof...
- Systemic autoimmune disease
External links
- The Autoimmunity Blog
- Autoimmunity – an Introduction Learning Unit on Chemgaroo
- American Autoimmune Related Diseases Association: a nonprofit advocacy
- Immune Tolerance Network: a research-oriented resource
- Nobel Prize The 1960 Nobel Prize in Physiology or Medicine was awarded to Frank M. Burnet and Peter B Medawar.
- http://www.nature.com/nature/journal/vaop/ncurrent/abs/nature07405.html Autoimmunity can be caused by environmental toxins
- The Immunology Database and Analysis Portal - an NIAID-funded database resource of reference and experiment data covering the entire immunology domain