Alternative pathway activation by nephritic factor complement c3 c5 convertases. Medical search. Frequent questions

C3 nephritic factor is a serum immunoglobulin G that interacts with the C3bBb alternative pathway convertase to activate C3. (medscape.com)
Alternate pathway activation occurs when components of microbial cell surfaces (eg, yeast walls, bacterial cell wall lipopolysaccharide [endotoxin]) or immunoglobulin (eg, nephritic factor, aggregated IgA) cleave small amounts of C3. (msdmanuals.com)

Small amounts of C3b are constantly being formed in the circulation, which are inactivated by factors H and I. The binding of C3b to a foreign antigen decreases its affinity for factor H and allows for the formation of increasing amounts of the alternate pathway convertase. (medscape.com)
The classic and alternate pathway convertases cause C3 activation, forming C3a and C3b. (medscape.com)
1986) reported a consanguineous Algerian family in which 2 brothers had early-onset glomerulonephritis with C3 deposits and low levels (less than 10% of normal) of complement factor H . The factor H deficiency was defined by undetectable complement hemolytic activity by the classic (CH50) and alternate (AP50) pathways, and low levels of C3 and factor B (138470). (findzebra.com)
Activation of alternate complement pathway has been demonstrated in most patients. (medscape.com)
Activation of an alternate complement pathway, C3 hypocomplementemia with lysis of adipocytes induced by C3NeF, has been implicated. (medscape.com)

Lipodystrophy is often associated with glomerulonephritis, low C3 serum complement levels, and the presence of a C3 nephritic factor. (medscape.com)
1982) reported 2 families with partial factor H deficiency and glomerulonephritis. (findzebra.com)
[ 4 ] Patients with membranoproliferative glomerulonephritis are more likely to have low C3 levels and the presence of C3 nephritic factor (C3NeF). (medscape.com)

Adipocytes synthesize C3, factor B, and factor D (adipsin), which allows C3bBb to be formed locally, but which usually does not result in the activation of the terminal lytic part of the complement pathway (C5-9).The IgG antibody, C3Nef, prevents the alternative complement C3-convertase C3Bb from dissociative inactivation, resulting in adipocyte lysis. (medscape.com)
More than 80% of patients with MPGN II are positive for serum C3 nephritic factor (C3NeF), an autoantibody directed against C3bBb, the convertase of the alternative pathway of the complement cascade. (findzebra.com)
C3NeF prolongs the half-life of C3 convertase. (findzebra.com)
Patients with MPGN type II without C3NeF often have mutations in the CFH gene, which also results in prolonged activation of C3 convertase. (findzebra.com)

C3 nephritic factor induces the lysis of adipocytes that secrete adipsin, a product identical to complement factor D. The distribution of the lipoatrophy is postulated to be dictated by the variable amounts of adipsin secreted by the adipocytes at different locations. (medscape.com)
Model of the adipocyte destruction in acquired partial lipodystrophy showing complement activation at the adipocyte surface resulting in adipocyte lysis. (medscape.com)

Both sexes are affected equally, with the diagnosis usually made in children between the ages of 5 and 15 years who present with nonspecific findings such as hematuria, proteinuria, acute nephritic syndrome, or nephrotic syndrome. (findzebra.com)
It is a representative disease of acute nephritic syndrome in which inflammation of the glomerulus is manifested by proliferation of cellular elements secondary to an immunologic mechanism (see the following image). (medscape.com)

C3b is an opsonin itself, and C3 convertase facilitates the activation of the terminal pathway and the formation of the membrane attack complex C5b-9. (medscape.com)
C3 cleavage may result in formation of the membrane attack complex (MAC), the cytotoxic component of the complement system. (msdmanuals.com)

Adipocytes synthesize factor D, the limiting component of the alternative complement pathway, which cleaves C3-bound factor B to its active enzymatic form. (medscape.com)
The classical, lectin, and alternative pathways converge into a final common pathway when C3 convertase (C3 con) cleaves C3 into C3a and C3b. (msdmanuals.com)

The classic pathway is activated by the interaction of C1 with an antigen-antibody complex. (medscape.com)
This interaction results in the formation of C4b2a, which is the classic pathway C3b convertase. (medscape.com)
1987) studied a family in which 3 female sibs had undetectable levels of factor H and C3 nephritic factor, low levels of factor B, C3, and C5 (see 120500), and normal levels of C4-binding protein (120830), factor I (217030), and classic pathway factors. (findzebra.com)

Clinical presentations are similar for the three types of MPGN, but they manifest somewhat different mechanisms of complement activation and predisposition to recur in kidney transplants. (medscape.com)
2006) summarized features of MPGN relevant to the complement cascade. (findzebra.com)

Laboratory features usually include decreased serum levels of factor H , complement component C3 (120700), and a decrease in other alternative pathway components, indicating activation of the alternative complement pathway. (findzebra.com)
In 1 family, of Polish origin, a teenaged male had vasculitis, thrombocytopenia, proteinuria, and depressed levels of serum factor H and complement component C3. (findzebra.com)
The index case had depressed serum factors H and B levels and IgA nephropathy (161950) which progressed to renal failure. (findzebra.com)
A sister also had IgA nephropathy and depressed serum H and C3 levels. (findzebra.com)

Hypocomplementemia results from increased catabolism and decreased C3 synthesis. (medscape.com)
[ 11 , 12 ] C3 hypocomplementemia likely contributes to the association of this syndrome with autoimmune diseases and with a propensity for patients to acquire bacterial infections. (medscape.com)

Complement factor H deficiency (CFHD) can manifest as several different phenotypes, including asymptomatic, recurrent bacterial infections, and renal failure. (findzebra.com)
See also complement factor I deficiency (610984), which shows phenotypic overlap with this disorder. (findzebra.com)
1993) described a consanguineous Italian family in which 3 sibs had deficiency of factor H and its spliced isoform FHL1. (findzebra.com)

Low C3 levels are present in approximately 75% of patients with this condition. (medscape.com)
Electron microscopy of renal biopsies from both patients were typical for intramembranous dense deposit disease, but immunofluorescence microscopy showed an atypical pattern with abundant granular C3 deposits within the mesangium and along the capillary walls. (findzebra.com)

Another form of lipodystrophy that fits the classification of "acquired partial" not involving the complement pathway is associated with hematopoietic stem cell transplantation (HSCT) to treat leukemia or neuroblastoma. (medscape.com)

Classical pathway components are labeled with a C and a number (eg, C1, C3), based on the order in which they were identified. (msdmanuals.com)

The normal complement system consists of the classic and alternative pathways. (medscape.com)
The complement system is an enzyme cascade that helps defend against infection. (msdmanuals.com)

Factor D is expressed to a higher extent in the fat cells of the upper half of the body compared with the lower half, and it is possibly this regional difference that accounts for the restriction of fat loss to the head, arms, and trunk. (medscape.com)

The classical pathway is activated by an antibody binding to a target antigen, forming a complex. (aacc.org)
C- reactive protein can also activate the classical pathway. (aacc.org)
The lectin pathway is analogous to the classical pathway, except that the triggers for its activation are bacteria containing mannose on its cellular membranes. (aacc.org)
In the classical pathway, an immune complex formation exposes sites in the Fc fraction of immunoglobulins that will allow attachment of C1q, which is the first subcomponent of complement. (aacc.org)
For the lectin pathway, bacteria containing mannose are identified by the recognition molecule mannose binding lectin (MBL) and its associated proteases, mannose associated proteases 1 and 2 (MASP 1 and 2), both of which are structurally very similar to the C1 complex formed in the classical pathway. (aacc.org)
17. Formation of high affinity C5 convertase of the classical pathway of complement. (nih.gov)
Classical pathway components are labeled with a C and a number (eg, C1, C3), based on the order in which they were identified. (msdmanuals.com)
This pathway otherwise resembles the classical pathway structurally and functionally. (msdmanuals.com)
The classical pathway is initiated when the C1qrs complex binds the Fc region of IgG or IgM. (kireportscommunity.org)

C3 nephritic factors are autoantibodies that prolong the half-life or prevent regulation of the alternative pathway C3 convertase, resulting in uncontrolled complement activation. (nih.gov)
This tight regulation of the alternative pathway can be dysregulated through several mechanisms . (kireportscommunity.org)

Three nephritic antibodies are described in MPGN that play a role in the development of hypocomplementemia[3, 4] : (1) nephritic factor of the classic pathway (NFc or C4NeF), (2) nephritic factor of the amplification loop (NFa or C3NeF), and (3) nephritic factor of the terminal pathway (NFt). (medscape.com)
Adipocytes synthesize C3, factor B, and factor D (adipsin), which allows C3bBb to be formed locally, but which usually does not result in the activation of the terminal lytic part of the complement pathway (C5-9).The IgG antibody, C3Nef, prevents the alternative complement C3-convertase C3Bb from dissociative inactivation, resulting in adipocyte lysis. (medscape.com)
[ 4 ] Patients with MPGN are more likely to have low C3 levels and the presence of C3 nephritic factor (C3NeF). (medscape.com)
Activation of an alternate complement pathway, C3 hypocomplementemia with lysis of adipocytes induced by C3NeF, has been implicated. (medscape.com)

Representative properdin-independent nephritic factors had no effect on C5 cleavage and terminal pathway activity, while properdin-dependent nephritic factors enhanced activity. (nih.gov)
Biacore analysis of four purified IgG samples confirmed resistance to decay and showed that properdin-independent nephritic factors increased convertase half-life over 50-fold, whereas properdin-dependent nephritic factors increased the half-life 10- to 20-fold and also increased activity of the C3 convertase up to 10-fold. (nih.gov)
20. Alternative pathway of complement: demonstration and characterization of initiating factor and its properdin-independent function. (nih.gov)

The classic pathway is activated by the interaction of C1 with an antigen-antibody complex. (medscape.com)
Multimerization and the presence of complement overcome the limited ability of monomeric antibody to mediate internalization of HIV-1 virions and may thus provide a therapeutic approach to clearing virus. (bvsalud.org)
Therefore, antibody multimerization in combination with complement may overcome the limited ability of monomeric antibody to mediate internalization of HIV-1 virions. (bvsalud.org)

11. Pathways of complement activation in membranoproliferative glomerulonephritis and allograft rejection. (nih.gov)

C3 cleavage may result in formation of the membrane attack complex (MAC), the cytotoxic component of the complement system. (msdmanuals.com)

This entire process is called the C3 amplification loop. (aacc.org)

Factor I, with cofactors including membrane cofactor protein (CD46), inactivates C3b and C4b. (msdmanuals.com)
The complement system is composed of more than 30 soluble and membrane-bound proteins which make up the classical, lectin-binding, and alternative pathways. (kireportscommunity.org)

The first and most common way are autoantibodies that stabilize C3 convertase thereby delaying its decay. (kireportscommunity.org)
These autoantibodies are referred to as C3 nephritic factors (C3NeFs). (kireportscommunity.org)

Complement inhibition with a terminal pathway blocker may alter disease course in some individuals. (nih.gov)

Forty-two of 48 nephritic factors tested prevented convertase decay by factor H, and most of these by decay accelerating factor (28) and complement receptor 1 (34). (nih.gov)
4. Properdin- and nephritic factor-dependent C3 convertases: requirement of native C3 for enzyme formation and the function of bound C3b as properdin receptor. (nih.gov)

Clinical presentations are similar for the three types of MPGN, but they manifest somewhat different mechanisms of complement activation and predisposition to recur in renal transplants. (medscape.com)
The complement system is an important part of innate immune response, and it is also considered to have major effector mechanisms in humoral immunity. (aacc.org)
12. Activation of the alternative complement pathway due to resistance of zymosan-bound amplification convertase to endogenous regulatory mechanisms. (nih.gov)

In the presence of properdin, binding of autoantibody was detected in 39 samples and convertase stabilization was detected in 36. (nih.gov)
9. Properdin: binding to C3b and stabilization of the C3b-dependent C3 convertase. (nih.gov)

C3 glomerulopathy (C3G) is a complex ultra-rare complement-mediated renal disease caused by uncontrolled activation of the complement alternative pathway (AP) in the fluid phase (as opposed to cell surface) that is rarely inherited in a simple mendelian fashion. (nih.gov)
C3 glomerulopathy (C3GN) is a term introduced around a decade ago to describe the clinical phenotype of glomerular disease arising from an overactivation of the alternative complement pathway. (kireportscommunity.org)

The complement system consists of a group of proteins that are activated in sequential steps, similarly to the coagulation cascade. (aacc.org)
The complement system is activated by the recognition of cleaved complement proteins by receptors on leukocytes and vascular cells. (aacc.org)
Complement proteins are produced mainly in the liver, but also by macrophages, monocytes, and epithelial cells in the urogenital and gastrointestinal tracts. (aacc.org)
For each of the pathways, the recognition molecule that will trigger activation of complement is different, and so are some of the proteins involved in each of the cascades. (aacc.org)
3. Activation of the alternative complement pathway with rabbit erythrocytes by circumvention of the regulatory action of endogenous control proteins. (nih.gov)
13. The binding of human complement proteins C5, factor B, beta 1H and properdin to complement fragment C3b on zymosan. (nih.gov)
18. Initiation of the alternative pathway of complement: recognition of activators by bound C3b and assembly of the entire pathway from six isolated proteins. (nih.gov)
These pathways are complex and a good portion of their Rube Goldberg nature can be explained by the fact that many of these proteins are zymogens which need to be cleaved in order to become active. (kireportscommunity.org)

14. Mechanism of complement inactivation by glycoprotein C of herpes simplex virus. (nih.gov)

The definitive diagnosis of C3G requires a renal biopsy with specialized immunofluorescence and electron microscopy studies both for diagnosis and to distinguish between the two major subtypes of C3G: C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). (nih.gov)
Treatment of C3GN: What's next for complement's alternative pathway? (kireportscommunity.org)
This trend is notably seen with ANCA vasculitis and anti-GBM disease, but the C3GN definition was special due to the existence of the complement inhibitor, eculizumab - a treatment that could benefit this group specifically. (kireportscommunity.org)
The potential treatments for C3GN have now expanded with the development of iptacopan which targets the alternative complement pathway. (kireportscommunity.org)

Next, C3b associates with Bb to form C3bBb, a C3 convertase that in turn amplifies the entire process noted above. (kireportscommunity.org)

Hypocomplementemia results from increased catabolism and decreased C3 synthesis. (medscape.com)

The lectin-binding pathway is initiated when hexamers of mannose-binding lectins bind bacterial carbohydrate motifs and associated with MBL-associated serine proteases to cleave C4 and C2 to again form the C4bC2b C3 convertase. (kireportscommunity.org)

In addition, spontaneous activation from hydrolysis of C3 occurs and generates C3b. (aacc.org)

Measurement by radial immunodiffusion and by inhibition of formation of properdin pathway C3 convertase. (nih.gov)

Here we optimized and compared a panel of assays to identify and interrogate nephritic factor activities. (nih.gov)
The objectives of this Pearl of Laboratory Medicine include a brief overview of the complement pathways, pre-analytical challenges for common analytes tested in the laboratory, analytical methods, and post-analytical challenges related to complement assays. (aacc.org)

which will be cleaved by Factor D to form a fluid phase C3 convertase. (aacc.org)

8. Properdin: initiation of alternative complement pathway. (nih.gov)
In contrast, the initiation of the alternative pathway is distinct in the fact that activation is continuous (figure 2). (kireportscommunity.org)

Close monitoring of renal function by a nephrologist with familiarity with the C3G disease spectrum, complete biannual assessment of the complement pathway, periodic eye examinations to evaluate the fundus. (nih.gov)
If the family history is positive for renal disease, evaluation of apparently asymptomatic at-risk relatives can include molecular genetic testing (if the pathogenic variants in the family are known), urinalysis, and comprehensive analysis of the complement system. (nih.gov)

This pathway is regulated by properdin, factor H, and decay-accelerating factor (CD55). (msdmanuals.com)

Complement participates in innumerous autoimmune and infectious processes. (aacc.org)

IgM has the greatest ability to activate complement among all immunoglobulins. (aacc.org)

This pathway is regulated by C1 inhibitor (C1-INH). (msdmanuals.com)

There are three pathways that are responsible for activation of the complement system and they differ in their mechanism of activation. (aacc.org)

In contrast, complement had little if any impact on internalization of monomer-opsonized virus. (bvsalud.org)

The complement system is an enzyme cascade that helps defend against infection. (msdmanuals.com)

The complement system is one of the cornerstones of the innate immune response. (aacc.org)
Complement also provides a bridge between innate and adaptive immune responses through receptors on lymphocytes and antigen-presenting cells. (aacc.org)

We found that, in the absence of complement, immune complexes consisting of HIV-1 virions and VRC01 multimers were slightly more efficiently internalized than were complexes formed with monomeric VRC01. (bvsalud.org)
The presence of complement, however, greatly augmented internalization of immune complexes formed with the multimeric MAb but had little impact on monomeric MAb-mediated internalization. (bvsalud.org)

There is a surveillance role for the alternative pathway, mediated by continuous hydrolysis of one complement component called C3. (aacc.org)
15. Analysis of the interactions between properdin, the third component of complement (C3), and its physiological activation products. (nih.gov)
16. The conversion of human complement component C5 into fragment C5b by the alternative-pathway C5 convertase. (nih.gov)

10. Control of the amplification convertase of complement by the plasma protein beta1H. (nih.gov)

Low C3 levels are present in approximately 75% of patients with this condition. (medscape.com)
Lipodystrophy is often associated with glomerulonephritis, low C3 serum complement levels, and the presence of a C3 nephritic factor. (medscape.com)

Properdin bound to microorganisms such as Neisseria or damaged cells can recruit C3b and activate the alternative pathway as well. (aacc.org)

The alternative pathway utilizes C3 and factors B and D to form the alternative pathway convertase C3b,Bb. (medscape.com)
Another form of lipodystrophy that fits the classification of "acquired partial" not involving the complement pathway is associated with hematopoietic stem cell transplantation (HSCT) to treat leukemia or neuroblastoma. (medscape.com)

6. The natural modulation of the amplification phase of complement activation. (nih.gov)

AMG 966 is a bi-specific, heteroimmunoglobulin molecule that binds both tumor necrosis factor alpha (TNFα) and TNF-like ligand 1A (TL1A). (bvsalud.org)

5. Complement C3 convertase: cell surface restriction of beta1H control and generation of restriction on neuraminidase-treated cells. (nih.gov)

Although discovered back in the 19th century, testing for complement abnormalities has regained interest in the last decade. (aacc.org)

Anatomy4

Organisms2

Diseases5

Chemicals and Drugs74

Analytical, Diagnostic and Therapeutic Techniques and Equipment3

Phenomena and Processes16

Information Science3

Immunoglobulin2

Alternate5

Glomerulonephritis3

C3Nef4

Lysis2

Acute nephriti2

Formation of the membrane attack2

Cleaves2

Classic pathway3

MPGN2

Serum4

Hypocomplementemia2

Deficiency3

Patients2

Partial1

Components1

System2

Lower1

Classical pathway9

Regulation of the alternative pathway2

C3NeF4

Properdin-independent3

Antibody3

Membranoproliferative glomerulonephritis1

Cleavage1

Amplification loop1

Membrane2

Autoantibodies2

Terminal1

Receptor2

Mechanisms3

Stabilization2

Glomerulopathy2

Proteins8

Inactivation1

C3GN4

C3bBb1

Hypocomplementemia1

Cleave1

Spontaneous1

Inhibition1

Assays2

Fluid phase1

Initiation2

Renal2

Decay accele1

Autoimmune1

Immunoglobulins1

Inhibitor1

Mechanism1

Contrast1

Enzyme1

Innate2

Immune complexes2

Component3

Protein1

Levels2

Bound1

Form2

Phase1

Specific1

Cell surface1

Decade1