Genetics of the Complement System

Alper, Chester A.; Rosen, Fred S.

doi:10.1007/978-1-4757-0659-8_4

Cited by 65 publications

(19 citation statements)

References 155 publications

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“…Allotypes of C3 and factor B have been carefully evaluated for functional activity and these variants have been demonstrated to possess similar hemolytic efficiency (14,15). There is one report suggesting differences in opsonic activity among C3 allotypes (16). In the uncommon variant of hereditary angioedema, normal or elevated concentrations of a nonfunctional C1 esterase inhibitor molecule are present (16,17) and this molecule does not inhibit the ability of C lg to split its natural substrates.…”

Section: Discussionmentioning

confidence: 99%

“…There is one report suggesting differences in opsonic activity among C3 allotypes (16). In the uncommon variant of hereditary angioedema, normal or elevated concentrations of a nonfunctional C1 esterase inhibitor molecule are present (16,17) and this molecule does not inhibit the ability of C lg to split its natural substrates. One difference between these previously described variations in the complement system and that of the S ~7 C4 molecule is that the former presumably represent single amino acid substitutions, whereas the latter is an apparent difference of ~2,000 daltons.…”

Section: Discussionmentioning

confidence: 99%

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A murine C4 molecule with reduced hemolytic efficiency.

Atkinson¹,

McGinnis²,

Brown³

et al. 1980

The Journal of Experimental Medicine

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C4 functional activity and antigenic levels were determined in H-2-congenic mouse strains. In strains with the H-2w7 haplotype, the C4 hemolytic activity per unit of residual Ss antigenic activity, after depletion of the nonfunctional Slp-positive molecules was 25-33% that found with other H-2 haplotypes. This reduced hemolytic efficiency was not the result of either a more labile C4 molecule or of the presence of inhibitors. Moreover, other strains with comparable antigenic concentrations of Ss (C4) and Slp has three- to fourfold higher levels of C4 hemolytic activity. Based on these data and previously reported structural differences between C4 molecules from the H-2w7 haplotype compared with other standard H-2 haplotypes, the reduced hemolytic efficiency of this molecule is probably secondary to alterations in the structure of its alpha-chain.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A murine C4 molecule with reduced hemolytic efficiency.

Atkinson¹,

McGinnis²,

Brown³

et al. 1980

The Journal of Experimental Medicine

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“…For a historical perspective, the reader is referred to an excellent review by Colten (1976). Many studies have clearly demonstrated that the liver is the primary site of synthesis of most of the complement components (reviewed in Colten, 1976;Perlmutter and Colten, 1986;Burger, 1988;Cole and Colten, 1988;DiScipio et ai, 1988), with hepatocytes producing over 90% of serum complement (Alper and Rosen, 1976). Hepatocytes synthesize all the components, with the possible exception of factor D, the receptors for C3 ligands (CR1-CR4), and properdin (Table 2).…”

Section: Tissue Sites Of Complement Synthesismentioning

confidence: 99%

Complement Biosynthesis in the Central Nervous System

Barnum

1995

Critical Reviews in Oral Biology & Medicine

187

103

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ABSTRACT:Complement is an important effector arm of the human immune response. Binding of proteolytic fragments derived from activation of complement by specific receptors leads to responses as diverse as inflammation, opsonization, and B-cell activation. The importance of characterizing the expression and regulation of complement in the CNS is highlighted by growing evidence that complement plays a significant role in the pathogenesis of a variety of neurological diseases, such as multiple sclerosis and Alzheimer's disease. \n vitro studies have demonstrated that astrocytes, the predominant glial cell type in the brain, are capable of expressing or producing a majority of the components of the complement system. Expression of many complement proteins synthesized by astrocytes is regulated by both pro-and anti-inflammatory cytokines, many of which are also produced by several cell types in the CNS. In addition to astrocytes, ependymal cells, endothelial cells, microglia, and neurons have recently been shown to synthesize various complement proteins or express complement receptors on their cell surfaces. Together, these studies demonstrate that several cell types throughout the brain have the potential to express complement and, in many cases, increase expression in response to mediators of the acute phase response. These studies suggest that complement may play a greater role in CNS immune responses than previously thought, and pave the way for better understanding of the dynamics of complement expression and regulation in vivo. Such understanding may lead to therapeutic manipulation of complement host defense functions in a variety of inflammatory and degenerative diseases in the CNS.

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“…Inherited deficiency states for almost all complement proteins, including inhibitors, have been described (11), including deficiency of C8 in three families (12)(13)(14). The availability of C8-deficient serum from one affected individual (12) made possible the present study which is concerned with genetic structural polymorphism in human C8.…”

mentioning

confidence: 98%

Genetic control of the eighth component of complement.

Raum¹,

Spence

Balavitch

et al. 1979

J. Clin. Invest.

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A B S T R A C T Using isoelectric focusing in polyacrylamide gel and a hemolytic assay for development of patterns, extensive structural polymorphism in human C8 has been delineated. Two C8 allotypes have been determined for two previously studied familes, each with a homozygous C8-deficient propositus. This study suggests that C8 deficiency is a silent or null allele of the C8 structural locus, and that half normal levels of C8 cannot be used as a single criterion for the establishment of heterozygous C8 deficiency. C8 allotypes, as well as 18 other autosomal markers, were also determined for 24 familes. The C8 structural locus is not closely linked to these markers, including the human histocompatibility loci complex.

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Genetics of the Complement System

Cited by 65 publications

References 155 publications

A murine C4 molecule with reduced hemolytic efficiency.

A murine C4 molecule with reduced hemolytic efficiency.

Complement Biosynthesis in the Central Nervous System

Genetic control of the eighth component of complement.

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