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43-434: IEI may mean: Inborn errors of immunity , genetic mutations that cause an increased susceptibility to disease Idiopathic environmental intolerance, also known as multiple chemical sensitivity Institute for Emerging Issues Institution of Engineers (India) Institut d'échanges interculturels Institution of Engineers of Ireland Intensive English Institute , at

86-663: A PID, PIRDs, and/or IEM. In 1973, the World Health Organization (WHO) established the Inborn Errors of Immunity Committee for the purpose of classifying and identifying immune defects in humans. The committee focused on rare immune diseases. In the 1990s, the WHO decided to focus on more common diseases, and the committee was taken on by the International Union of Immunological Societies (i.e., IUIS). This relationship

129-461: 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

172-406: A biochemical rather than a clinical discipline. By the 1950s, the modern understanding of autoantibodies and autoimmune diseases started to spread. More recently, it has become accepted that autoimmune responses are an integral part of vertebrate immune systems (sometimes termed "natural autoimmunity"). Autoimmunity should not be confused with alloimmunity . While a high level of autoimmunity

215-482: A defect in a pathway that metabolizes proteins, fats, or carbohydrates or that impairs the function of a subcellular organelle . This mutation usually causes a complicated medical condition involving several human organ systems. When any one of the disorders in the PID, PIRDs, or IEM classifications is caused by a single gene mutation that disrupts the immune system, it is termed an IEI. Consequently, many IEIs are also termed

258-956: A persistent increased risk for autoimmune disease. It has been suggested that the slight, direct 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. 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 hypothesis attributes these correlations to

301-619: A variety of aberrant ways. There are a large number of immunodeficiency syndromes that present clinical and laboratory characteristics of autoimmunity. The decreased ability of the immune system to clear infections in these patients may be responsible for causing autoimmunity through perpetual immune system activation. One example is common variable immunodeficiency , in which multiple autoimmune diseases are seen, e.g., inflammatory bowel disease, autoimmune thrombocytopenia and autoimmune thyroid disease. Familial hemophagocytic lymphohistiocytosis , an autosomal recessive primary immunodeficiency,

344-466: Is also sometimes associated with the development of autoimmune and atopic phenomena. 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: The first two, which are involved in

387-759: Is also termed Bruton's agammaglobulinemia and the gene that when mutated causes this disease is termed the Bruton's tyrosine kinase , i.e., BKT , gene. The product of this gene, the BTK protein, contributes indirectly to promoting the production of all the antibody subtypes, i.e., IgG , IgA , IgM , and IgE . Impairments in the immune system's protective actions have been referred to as primary immunodeficiencies (PID), i.e., immune deficiencies that are present at birth and not caused by secondary factors such as other diseases or exposure to genotoxic agents. The PID disorders (see List of primary immunodeficiencies ) and its subgroup,

430-594: Is another example. Pancytopenia , rashes, swollen lymph nodes and enlargement of the liver and spleen are commonly seen in such individuals. Presence of multiple uncleared viral infections due to lack of perforin are thought to be responsible. In addition to chronic and/or recurrent infections many autoimmune diseases including arthritis, autoimmune hemolytic anemia, scleroderma and type 1 diabetes mellitus are also seen in X-linked agammaglobulinemia (XLA). Recurrent bacterial and fungal infections and chronic inflammation of

473-503: Is different from Wikidata All article disambiguation pages All disambiguation pages Inborn errors of immunity A human immune disease that would later be classified as an IEI was first defined by Ogden Bruton . In the early 1950s, he examined an 8-year-old boy who had 19 episodes of pneumonia over a period of 4 years. Expecting that individuals with such a history of repeated infections would have high levels of infection-fighting antibodies in their serum , Dr. Bruton

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516-914: Is involved in regulating the activity of immune cells, and so variations in this gene can lead to dysregulation of the immune response, making individuals more susceptible to autoimmune diseases. Most autoimmune diseases are sex-related ; a s a whole, women are much more likely to develop autoimmune disease than men. Being female is the single greatest risk factor for developing autoimmune disease than any other genetic or environmental risk factor yet discovered. Autoimmune conditions overrepresented in women include: lupus , primary biliary cholangitis , Graves' disease , Hashimoto's thyroiditis , and multiple sclerosis , among many others. A few autoimmune diseases that men are just as or more likely to develop as women include: ankylosing spondylitis , type 1 diabetes mellitus , granulomatosis with polyangiitis , primary sclerosing cholangitis , and psoriasis . The reasons for

559-560: Is overexpressed, or directs the formation of a product with reduced, increased, or no activity. Furthermore, the defective IEI gene in parents may not be expressed in their offspring depending on the IEI gene's dominant or recessive activity or may not be present in offspring depending on its location in the X chromosome , Y chromosome , or one of 46 remaining non-sex chromosomes (termed autosomes ; see sex linkage ). Individuals who do inherit an IEI gene may still not exhibit symptoms because: a)

602-508: Is present in all individuals, even in normal health state. It causes autoimmune diseases if self-reactivity can lead to tissue damage. In the later 19th century, it was believed that the immune system was unable to react against the body's own tissues. Paul Ehrlich , at the turn of the 20th century, proposed the concept of horror autotoxicus . Ehrlich later adjusted his theory to recognize the possibility of autoimmune tissue attacks, but believed certain innate protection mechanisms would prevent

645-594: Is the ability of an individual to ignore "self", while reacting to "non-self". This breakage leads to the immune system mounting an effective and specific immune response against self antigens. 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

688-450: Is unhealthy, a low level of autoimmunity may actually be beneficial. Taking the experience of a beneficial factor in autoimmunity further, one might hypothesize with intent to prove that autoimmunity is always a self-defense mechanism of the mammal system to survive. The system does not randomly lose the ability to distinguish between self and non-self; the attack on cells may be the consequence of cycling metabolic processes necessary to keep

731-731: The antigen pigeon cytochrome c peptide, as determined by ZAP70 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. Pioneering work by Noel Rose and Ernst Witebsky in New York, and Roitt and Doniach at University College London provided clear evidence that, at least in terms of antibody-producing B cells (B lymphocytes), diseases such as rheumatoid arthritis and thyrotoxicosis are associated with loss of immunological tolerance , which

774-411: The primary immune regulatory disorders (PIRDs; i.e., disorders of immunity characterized as excessive proliferations of lymphocytes and the development of immune responses against one's own normal tissues ), are immune disorders similar to those in IEI. Finally, inborn errors of metabolism (i.e., IEM) are a group of about 1700 disorders caused by a mutation in any one of about 1500 genes that causes

817-700: 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 lupus erythematosus ). In recent studies, the gene PTPN22 has emerged as a significant factor linked to various autoimmune diseases, such as Type I diabetes, rheumatoid arthritis, systemic lupus erythematosus, Hashimoto's thyroiditis, Graves' disease, Addison's disease, Myasthenia Gravis, vitiligo, systemic sclerosis, juvenile idiopathic arthritis, and psoriatic arthritis. PTPN22

860-611: The University of Illinois Urbana-Champaign Intuitive Ethical Introvert, in socionics theory Iran Electronics Industries Topics referred to by the same term [REDACTED] This disambiguation page lists articles associated with the title IEI . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=IEI&oldid=1155896283 " Category : Disambiguation pages Hidden categories: Short description

903-436: 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

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946-433: The autoimmune response from becoming pathological. 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. During the following decades, a number of conditions could be linked to autoimmune responses. However, the authoritative status of Ehrlich's postulate hampered the understanding of these findings. Immunology became

989-642: The blood chemistry in homeostasis. Second, autoimmunity may have a role in allowing a rapid immune response in the early stages of an infection when the availability of foreign antigens 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-2 ) to temporarily prevent CD4+ T cell-MHC interaction. Naive CD4+ T cells (those that have not encountered non-self antigens before) recovered from these mice 36 hours post-anti-MHC administration showed decreased responsiveness to

1032-545: 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

1075-414: The dysfunctional gene in some but not their tissues (see mosaicism ). Thus, the prevalence of IEIs in 2023 was estimated to be between 1 in 1,000 and 1 in 5,000 individuals but this may be an underestimate: its true prevalence may turn out to be as high as 1 in 500 individuals. As with other human genes, an IEI gene may be defective because it is not expressed (see gene expression ), is under expressed,

1118-538: The effects of smoking correlate with the presence of antibodies to citrullinated peptides . 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: The roles of specialized immunoregulatory cell types, such as regulatory T cells , NKT cells , γδ T-cells in

1161-520: The expression of the IEI gene without changing this gene's nucleic acid sequence (termed epigenetic regulation ). Mosaicism , i.e., an IEI mutation arising after fertilization of an egg, has been shown to lead to offsspring with two different cell populations, one with and one without the IEI gene. Individuals with this mosaicism may develop a mild IEI disorder, an IEI disorder much later in life, or no IEI disorder. The International Union of Immunological Societies (2022) has classified IEI disorders into

1204-885: The following 10 categories: Autoimmunity In immunology , autoimmunity is the system of immune responses of an organism against its own healthy cells , tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an " autoimmune disease ". Prominent examples include celiac disease , diabetes mellitus type 1 , Henoch–Schönlein purpura , systemic lupus erythematosus , Sjögren syndrome , eosinophilic granulomatosis with polyangiitis , Hashimoto's thyroiditis , Graves' disease , idiopathic thrombocytopenic purpura , Addison's disease , rheumatoid arthritis , ankylosing spondylitis , polymyositis , dermatomyositis , and multiple sclerosis . Autoimmune diseases are very often treated with steroids . Autoimmunity means presence of antibodies or T cells that react with self-protein and

1247-508: The gene is under expressed (termed reduced penetrrance ) or not expressed (termed non-penetrance) in males or females (these different expression patterns are also termed gender-related penetrance ), b) the presence of other genes which modify the activity of the inherited IEI gene (termed genetic modifiers ), c) exposure to environmental factors with modify the activity of the inherited IEI gene (termed environmental modifiers ), and/or d) epigenetic , i.e., caused by factors which regulate

1290-416: 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

1333-808: The gut and lungs are seen in chronic granulomatous disease (CGD) as well. CGD is a caused by decreased production of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase by neutrophils. Hypomorphic RAG mutations are seen in patients with midline granulomatous disease; an autoimmune disorder that is commonly seen in patients with granulomatosis with polyangiitis and NK/T cell lymphomas. Wiskott–Aldrich syndrome (WAS) patients also present with eczema, autoimmune manifestations, recurrent bacterial infections and lymphoma. In autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy also autoimmunity and infections coexist: organ-specific autoimmune manifestations (e.g., hypoparathyroidism and adrenocortical failure) and chronic mucocutaneous candidiasis. Finally, IgA deficiency

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1376-653: 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

1419-570: The immune-manipulating strategies of pathogens. While 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 has autoimmune disease. The details of parasite immune modulation are not yet known, but may include secretion of anti-inflammatory agents or interference with

1462-469: 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. Diagnosis of autoimmune disorders largely rests on accurate history and physical examination of

1505-473: The pathogenesis of autoimmune disease are under investigation. 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. 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

1548-477: The patient, and high index of suspicion against a backdrop of certain abnormalities in routine laboratory tests (example, elevated C-reactive protein ). 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

1591-486: The progress of the disease. Treatments for autoimmune disease have traditionally been immunosuppressive , anti-inflammatory , or palliative . Managing inflammation is critical in autoimmune diseases. 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

1634-587: 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 lymphocytes capable of self-reactivity. Fewer correlations exist with MHC class I molecules. The most notable and consistent is the association between HLA B27 and spondyloarthropathies like ankylosing spondylitis and reactive arthritis . Correlations may exist between polymorphisms within class II MHC promoters and autoimmune disease. The contributions of genes outside

1677-592: The severity of celiac disease. Steroidal or NSAID treatment limits inflammatory symptoms of many diseases. IVIG is used for CIDP and GBS . Specific immunomodulatory 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

1720-448: The sex role in autoimmunity vary. 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

1763-429: 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

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1806-539: Was made official in 2008. The number of genes that when mutated to cause specific IEI disorders has steadily rose from less than 10 in the 1980s to the IUIS expert committee's 2022 classification of 485 mutated genes causing these disorders. These numbers are expected to increase further as DNA sequencing using automated methods (e.g., massive parallel sequencing ), further studies of less severe immune disorders, and analyses of multiple tissues in individuals that may have carry

1849-509: Was surprised to find that the boy had hypogammaglobulinemia , i.e., his serum lacked detectible levels of circulating antibodies which attack infection-causing microorganisms and virus. That same year, Dr. Bruton and colleagues published on two other infection-prone patients who also lacked detectable levels of these serum antibodies This particular from of hypogammaglobulinemia, now termed X-linked agammaglobulinemia and characterized as an IEI, occurs in about 1 per 379,000 live births. It

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