| Terminal complement pathway deficiency | |
|---|---|
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| complement membrane attack complex |
Terminal complement pathway deficiency is a genetic condition affecting the complement membrane attack complex (MAC).
It involves deficiencies of C5, C6, C7, and C8. (While C9 is part of the MAC, and deficiencies have been identified, [1] it is not required for cell lysis. [2] )
People with this condition are prone to meningococcal infection. [3] Vaccination may be recommended. [4]
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Suspect terminal complement pathway deficiency in patients with more than one Neisseria infection episode.
| C4 (C) | FB (A) | C3 | CH50 | Conditions |
|---|---|---|---|---|
| · | ↓ | ↓ | ↓ | PSG, C3 NeF AA |
| ↓ | · | ↓ | · | HAE, C4D |
| · | · | · | ↓ | TCPD |
| ↓ | ·/↓ | ↓ | ↓ | SLE |
| ↑ | ↑ | ↑ | ↑ | inflammation |
Initial complement tests often include C3 and C4, but not C5 through C9. Instead, the CH50 result may play a role in diagnosis: if the CH50 level is low but C3 and C4 are normal, then analysis of the individual terminal components may be warranted.
Patients with terminal complement pathway deficiency should receive meningococcal and pneumococcal vaccinations. They can receive live vaccines.
Waterhouse–Friderichsen syndrome (WFS) is defined as adrenal gland failure due to bleeding into the adrenal glands, commonly caused by severe bacterial infection. Typically, it is caused by Neisseria meningitidis.
The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen's cell membrane. It is part of the innate immune system, which is not adaptable and does not change during an individual's lifetime. The complement system can, however, be recruited and brought into action by antibodies generated by the adaptive immune system.
Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affect the patient's immune system. Examples of these extrinsic factors include HIV infection and environmental factors, such as nutrition. Immunocompromisation may also be due to genetic diseases/flaws such as SCID.
The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune system. The classical complement pathway is initiated by antigen-antibody complexes with the antibody isotypes IgG and IgM.
The alternative pathway is a type of cascade reaction of the complement system and is a component of the innate immune system, a natural defense against infections.
C3 convertase belongs to family of serine proteases and is necessary in innate immunity as a part of the complement system which eventuate in opsonisation of particles, release of inflammatory peptides, C5 convertase formation and cell lysis.
The membrane attack complex (MAC) or terminal complement complex (TCC) is a complex of proteins typically formed on the surface of pathogen cell membranes as a result of the activation of the host's complement system, and as such is an effector of the immune system. Antibody-mediated complement activation leads to MAC deposition on the surface of infected cells. Assembly of the MAC leads to pores that disrupt the cell membrane of target cells, leading to cell lysis and death.
Complement component 3, often simply called C3, is a protein of the immune system that is found primarily in the blood. It plays a central role in the complement system of vertebrate animals and contributes to innate immunity. In humans it is encoded on chromosome 19 by a gene called C3.
C5 convertase is an enzyme belonging to a family of serine proteases that play key role in the innate immunity. It participates in the complement system ending with cell death.
Meningococcal disease describes infections caused by the bacterium Neisseria meningitidis. It has a high mortality rate if untreated but is vaccine-preventable. While best known as a cause of meningitis, it can also result in sepsis, which is an even more damaging and dangerous condition. Meningitis and meningococcemia are major causes of illness, death, and disability in both developed and under-developed countries.
The lectin pathway or MBL pathway is a type of cascade reaction in the complement system, similar in structure to the classical complement pathway, in that, after activation, it proceeds through the action of C4 and C2 to produce activated complement proteins further down the cascade. In contrast to the classical complement pathway, the lectin pathway does not recognize an antibody bound to its target. The lectin pathway starts with mannose-binding lectin (MBL) or ficolin binding to certain sugars.
Complement component 9 (C9) is a MACPF protein involved in the complement system, which is part of the innate immune system. Once activated, about 12-18 molecules of C9 polymerize to form pores in target cell membranes, causing lysis and cell death. C9 is one member of the complement membrane attack complex (MAC), which also includes complement components C5b, C6, C7 and C8. The formation of the MAC occurs through three distinct pathways: the classical, alternative, and lectin pathways. Pore formation by C9 is an important way that bacterial cells are killed during an infection, and the target cell is often covered in multiple MACs. The clinical impact of a deficiency in C9 is an infection with the gram-negative bacterium Neisseria meningitidis.
Complement C2 is a protein that in humans is encoded by the C2 gene. The protein encoded by this gene is part of the classical pathway of the complement system, acting as a multi-domain serine protease. Deficiency of C2 has been associated with certain autoimmune diseases.
Eculizumab, sold under the brand name Soliris among others, is a recombinant humanized monoclonal antibody used to treat paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), generalized myasthenia gravis, and neuromyelitis optica. In people with PNH, it reduces both the destruction of red blood cells and need for blood transfusion, but does not appear to affect the risk of death. Eculizumab was the first drug approved for each of its uses, and its approval was granted based on small trials. It is given by intravenous infusion.
Properdin deficiency is a rare X-linked disease in which properdin, an important complement factor responsible for the stabilization of the alternative C3 convertase, is deficient. There are three forms of properdin deficiencies: Type I, which is identified by the total absence of the properdin protein in the plasma, Type II, which is a low but detectable amount of the properdin protein in the plasma, and Type III, which is a rare case of normal levels of properdin protein, but a dysfunctional variant. One of the first studied cases of properdin deficiency was in 1980 by Davis and Forrestal. These families had members with only partial deficiencies which resulted in a lowered consumption of the C3 protein. Properdin deficiency was studied again shortly after in 1982 by Sjoholm in which all of the subjects were deceased shortly after the study because of their disease. The largest study of properdin deficiency was in 1989 by Fijen which included nine males across three generations. Out of the 46 family members in Fijen's study, the 9 who were affected were found to be more susceptible to diseases from the Neisseria genus.
C3b is the larger of two elements formed by the cleavage of complement component 3, and is considered an important part of the innate immune system. C3b is potent in opsonization: tagging pathogens, immune complexes (antigen-antibody), and apoptotic cells for phagocytosis. Additionally, C3b plays a role in forming a C3 convertase when bound to Factor B, or a C5 convertase when bound to C4b and C2b or when an additional C3b molecule binds to the C3bBb complex.
Complement deficiency is an immunodeficiency of absent or suboptimal functioning of one of the complement system proteins. Because of redundancies in the immune system, many complement disorders are never diagnosed. Some studies estimate that less than 10% are identified. Hypocomplementemia may be used more generally to refer to decreased complement levels, while secondary complement disorder means decreased complement levels that are not directly due to a genetic cause but secondary to another medical condition.
NmVac4-A/C/Y/W-135 is the commercial name of the polysaccharide vaccine against the bacterium that causes meningococcal meningitis. The product, by JN-International Medical Corporation, is designed and formulated to be used in developing countries for protecting populations during meningitis disease epidemics.
Complement 3 deficiency is a genetic condition affecting complement component 3 (C3). People can suffer from either primary or secondary C3 deficiency. Primary C3 deficiency refers to an inherited autosomal-recessive disorder that involves mutations in the gene for C3. Secondary C3 deficiency results from a lack of factor I or factor H, two proteins that are key for the regulation of C3. Both primary and secondary C3 deficiency are characterized by low levels or absence of C3.
Total complement activity (TCA) refers to a series of tests that determine the functioning of the complement system in an individual.