Functionally active complement proteins C6 and C7 detected in C6- and C7-deficient individuals

Würzner, Reinhard; Orren, Ann; Potter, Paul; Morgan, B. Paul; Ponard, D.; Späth, Peter; Brai, M.; Schulze, Matthias; Happe, Ludger; Götze, Otto

doi:10.1111/j.1365-2249.1991.tb05656.x

Cited by 56 publications

(13 citation statements)

References 30 publications

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“…The terminal complement complex (TCC), which forms the membrane attack complex (MAC), is responsible for the lytic complement action. 8,9 The MAC plays a basic role in recHUS by inducing cell damage and probably also by inducing the typical symptoms of HUS. 9,10 In this study, we investigated TCC as a marker for MAC in patients with recHUS and in healthy controls.…”

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confidence: 99%

Terminal Complement Complex (C5b-9) in Children with Recurrent Hemolytic Uremic Syndrome

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Scheiring

Sautter

et al. 2006

Semin Thromb Hemost

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Recurrent hemolytic uremic syndrome (recHUS) is a heterogeneous group of disorders. The pathogenesis of recHUS is not fully understood. recHUS has a high risk of development of terminal renal insufficiency and other sequelae. Abnormalities in complement factor H or in membrane-bound complement inhibitors with consecutive complement activation can be found in approximately 30 to 50% of the patients. Starting in 2001, we evaluated 42 patients with recHUS from five European countries (Germany, Austria, Hungary, Switzerland, and the Czech Republic). We measured the terminal complement complex (TCC) by an enzyme-linked immunosorbent assay using a neoepitope-specific anti-C9 antibody in 17 patients in plasma (native complement activation), serum (after coagulation), and zymosan-activated serum (Z-serum; after stimulation of coagulation). We compared the results to those of 16 healthy persons. In patients with recHUS (eight males, nine females) with a median age of 10.8 years, the TCC values were higher in plasma (0.57 versus 0.48 microg/mL; P = 0.04) and serum (3.1 versus 2.2 microg/mL) than in those of the control group, with a median age of 28.6 years (six males, 10 females) The TCC values in patients with low C3 compared with patients with normal C3 levels were even higher in plasma and serum, and the ratio was much lower. Children with recHUS have higher concentrations of TCC in plasma and serum. The ratio of Z-serum to serum showed significantly lower values in children with recHUS (96.01 versus 150.3; P = 0.01). These findings indicate a higher grade of complement activation and consumption in recHUS, suggesting that TCC may mediate cell toxicity. This may play an important role in the inferior outcome of these patients. The isolated substitution of factor H, or other complement inhibitors to block TCC formation, may represent useful therapies for these patients.

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confidence: 99%

Terminal Complement Complex (C5b-9) in Children with Recurrent Hemolytic Uremic Syndrome

Prüfer

Scheiring

Sautter

et al. 2006

Semin Thromb Hemost

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“…Table 1 C7 concentration and CH50 activity in the serum of the members of family 1 and family 2 included in the study. The normal concentration of C7 in serum is 90 (±36) lg ⁄ ml [22].…”

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confidence: 99%

C7 Deficiency and Meningococcal Infection Susceptibility in Two Spanish Families

et al. 2010

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In this work, we report the genetic basis of C7 deficiency in two different Spanish families. In family 1, by using exon‐specific polymerase chain reaction and sequencing, a recently described mutation was found in homozygosity in the patient; a single base change in exon 15 (C2107T) leading to a stop codon that causes truncation of the C‐terminal portion of C7 (Q681X). Patient’s father, mother and sister were heterozygous for this mutation. Interestingly, patient’s parents were not related. In family 2, a new single base mutation in exon 2 (G90A), leading to a stop codon that causes the premature truncation of C7 (W8X), was found in the patient, mother and sister 1. Additionally, patient 2, her father and sisters, displayed a missense mutation in exon 9 (G1135C) resulting in a change of aminoacid (G357R). Although sister 1 bore the same mutations in the C7 gene that patient 2, she remains asymptomatic. Because both mutations were found in the patient and her sister, we analyse other defence mechanisms such as FcγR polymorphisms as well as mannose‐binding lectin alleles (MBL2 gene) and MBL levels. Results showed that both siblings bore identical combinations of FcγR allotypes and different MBL2 alleles, exhibiting patient 2 a MBL‐insufficient genotype. Normal MBL levels were found in patient 1 and in two previously studied C7‐deficient siblings, suggesting the involvement of other mechanisms of immunity distinct of FcγR variants and the MBL pathway, for the absence of meningococcal recurrent infections in certain C7‐deficient individuals.

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“…4 Four single base pair deletions, each causing a frame-shift mutation, have been found to be responsible for C6Q0; 5 the patients were either coloured or black. Three of the mutations were first reported in African-Americans, but the fourth (828delG) was first reported in coloured and black individuals.…”

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Complement component C5 and C6 mutation screening indicated in meningococcal disease in South Africa

et al. 2012

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Functionally active complement proteins C6 and C7 detected in C6- and C7-deficient individuals

Cited by 56 publications

References 30 publications

Terminal Complement Complex (C5b-9) in Children with Recurrent Hemolytic Uremic Syndrome

Terminal Complement Complex (C5b-9) in Children with Recurrent Hemolytic Uremic Syndrome

C7 Deficiency and Meningococcal Infection Susceptibility in Two Spanish Families

Complement component C5 and C6 mutation screening indicated in meningococcal disease in South Africa

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