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Factor H Autoantibodies

Factor H Autoantibodies

Autoantibodies to Factor H, can block the function of the control protein, allowing for inappropriate activation of the alternative pathway of complement. Factor H Autoantibody has been associated with atypical Hemolytic Uremic Syndrome (aHUS), also known as complement related HUS.

What does factor H do?

Factor H is a regulator of complement activation that blocks the formation of C3 convertase and is a cofactor for cleavage of C3b by factor I. Deficiencies of factor H result in unregulated elaboration of C3b on activation of the alternative pathway.

What is factor H in immunology?

Complement factor H is a soluble complement regulator essential for controlling the alternative pathway in blood and on cell surfaces. Normal recognition of self cell markers (i.e. polyanions) and C3b/C3d fragments is necessary for factor H function.

What is factor H test?

Factor H Level Assay. Dense Deposit Disease, C3 Glomerulonephritis and atypical Hemolytic Uremic Syndrome. Complement Factor H (FH; MW: 155 kDa) is an important fluid-phase and cell-surface regulator of alternative pathway (AP) activity.

What is atypical hemolytic uremic syndrome AHUS?

Atypical hemolytic-uremic syndrome is a disease that primarily affects kidney function. This condition, which can occur at any age, causes abnormal blood clots (thrombi) to form in small blood vessels in the kidneys. These clots can cause serious medical problems if they restrict or block blood flow.

What is factor H binding protein?

Factor H binding protein (fHbp) is a 27-kDa lipoprotein present on the surface of Neisseria meningitidis that improves the survival of the bacterium in human blood by binding human factor H (hfH), a down-regulator of the complement alternative pathway (1, 2).

What is complement deficiency?

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.

What produces factor H?

Factor H production is stimulated by IFN-? in human mesangial cells (van den Dobbelsteen et al., 1994). These cells are involved in the structure and function of normal glomerulus (Couser et al., 1985; Lesher et al., 2013). Low levels of properdin have been detected in renal diseases due to hypercatabolism.

What do Anaphylatoxins do?

Function. Anaphylatoxins are able to trigger degranulation (release of substances) of endothelial cells, mast cells or phagocytes, which produce a local inflammatory response. If the degranulation is widespread, it can cause a shock-like syndrome similar to that of an allergic reaction.

Is Factor HA protein?

Factor H is a member of the regulators of complement activation family and is a complement control protein. It is a large (155 kilodaltons), soluble glycoprotein that circulates in human plasma (at typical concentrations of 200300 micrograms per milliliter).

What is the main reason for hemolytic uremic syndrome?

What causes HUS? Most cases of HUS occur after an infection in the digestive tract caused by the E. coli bacterium, O157:H7. Diarrhea and upper respiratory infections are the most common factors leading to HUS.

Is hemolytic uremic syndrome fatal?

What is hemolytic uremic syndrome (HUS)? HUS is a rare condition that can lead to kidney failure in children. Kidney failure develops as a result of destruction of the small, functional structures and vessels inside the kidney. HUS is a serious illness and potentially fatal.

How rare is hemolytic uremic syndrome?

Typical hemolytic uremic syndrome (HUS) is an uncommon disease that occurs in 5 to 15 percent of individuals, especially children, who are infected by the Escherichia coli (E. coli) bacterium, usually O157:H7 but also 0104:H4.

What is activation of complement?

Complement is a system of plasma proteins that can be activated directly by pathogens or indirectly by pathogen-bound antibody, leading to a cascade of reactions that occurs on the surface of pathogens and generates active components with various effector functions.

What is fHBP?

fHBP is naturally a lipoprotein, and early preclinical studies by Fletcher et al. clearly demonstrated that lipidated fHBP vaccines were more immunogenic than the same variants expressed without the lipidation tail (21).

What are the four major functions of the complement system?

The complement system has four major function, including lysis of infectious organisms, activation of inflammation, opsonization and immune clearance. There are three different complement pathways, the classical complement pathway, the alternative complement pathway, and the mannose-binding lectin pathway.

What disease can cause a low complement level?

Low complement C4 levels under 15 milligrams per deciliter might indicate some types of health problems and conditions such as: Malnutrition. Lupus. Liver diseases such as hepatitis and cirrhosis.

What is the most serious complement deficiency?

C2 deficiency is the most common complement deficiency, with frequency estimates between 1 in 10,000 to 1 in 20,000 for homozygous C2-deficient patients.

What causes complement deficiencies?

Complement deficiency

Acquired deficiency can be caused by infection. MBL deficiency is thought to be the most common. Uncontrolled or deranged complement activity can also cause disease by promoting inflammation. The complement system can be involved in the pathogenesis of autoimmune diseases.

How is the alternative pathway activated?

The alternative pathway (AP) is slowly activated spontaneously by hydrolysis of the internal C3 thioester bond [1214] and further triggered by contact with various proteins, lipids and carbohydrate structures on microorganisms and other foreign surfaces [1, 15].

What is Properdin system?

Properdin is the only gene of the complement system that is encoded on the X chromosome. Properdin stabilizes the alternative pathway C3 and C5 convertases by extending the half-lives of the C3 and C5 converting enzymes. Properdin deficiency is inherited as an X-linked recessive trait.

Who discovered Properdin?

Properdin was first described over 50 years ago by Louis Pillemer and his collaborators as a vital component of an antibody-independent complement activation pathway. In the 1970’s properdin was shown to be a stabilizing component of the alternative pathway convertases, the central enzymes of the complement cascade.

How do anaphylatoxins cause inflammation?

Additionally, anaphylatoxins induce mast cell and basophil degranulation, which releases vasoactive substances such as histamine and serotonin, leading to vasodilation, thus increasing blood flow to areas of inflammation. C5a works to activate the immune system and mediate inflammation in a variety of ways.

How does C3a cause inflammation?

C3a, C4a, and particularly C5a trigger the degranulation of mast cells and basophils, which release the vasoactive amines that cause the increased vascular permeability and smooth muscle contraction characteristic of inflammation.

How does DAF help regulate the complement system?

DAF is a GPI-anchored membrane complement regulator that inhibits the C3 and C5 convertases of both the classical and alternative pathways.

How is C3 convertase formed?

The C3 convertase formed in the classical or lectin pathways is formed of C4b and C2b instead (NB: C2b, the larger fragment of C2 cleavage, was formerly known as C2a). The cleavage of C4 and C2 is mediated by serine proteases.

Which regulatory factors prevents Association of C9 with the Mac?

CD59 prevents polymerization of C9 by the complex C5bC6C7C8, thus preventing synthesis of MAC on normal cells.

What are the 5 symptoms of hemolytic uremic syndrome?

Symptoms of HUS include vomiting, bloody diarrhea (loose stool/poop), stomach pain, fever, chills, and headache. As infection progresses, persons may experience fatigue, weakness, fainting, bruising, and paleness.

How do you know if you have HUS?

Early symptoms of HUS include decreased urine output, diarrhea, and feeling slow and tired (lethargy). Low red blood cell count (anemia), low platelet count, and decreased kidney function are signs that might be detected by laboratory testing.

Can Covid cause hemolytic uremic syndrome?

It has been reported in the past that TMA/atypical HUS can relapse in the setting of viral illnesses like influenza. Some authors have suggested adding COVID-19 as a triggering factor for aHUS relapse.

Is hemolytic uremic syndrome curable?

More than 85 percent of patients with the most common form of HUS recover complete kidney function. However, even with full recovery, there is the chance for high blood pressure or other kidney problems in the years ahead.

Can HUS cause brain damage?

Heart and lung injury is rare in HUS, but can be fatal if it occurs. Brain damage (encephalopathy) can cause stroke or cerebral edema (swelling of the brain) and is the most frequent cause of death in HUS patients.

Can you survive HUS?

Although those surviving HUS usually escape immediate serious complications, about 3-5% are left with long-term damage to organs other than the kidneys, especially to the pancreas or brain. An equal number are left with severe kidney damage and, thus, require chronic dialysis and kidney transplant within a few years.

Can you live with aHUS?

In more than half of all patients, aHUS progresses to kidney failure, often within three years of diagnosis. Death rates among aHUS patients are as high as 25%.

What medications can cause hemolytic uremic syndrome?

Cisplatin, one of the most frequently used antineoplastic drugs, also induces HUS. Cyclosporin causes HUS, probably due to endothelial damage and/or an inhibition of prostacyclin synthesis. A case of FK506 induced HUS has been recently reported. Quinine and Cocaine also can induce HUS.

Can HUS cause liver damage?

During the recovery stage of the hemolytic uremic syndrome in 2 cases an increase of serum levels of GOT, GPT, LDH, gammaGT, 5’ND and AP was noticed, without signs of a recurrence of the disease. In one patient also jaundice and hepatomegaly were found. The observations suggest a parenchymal damage of the liver.

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