Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-19T12:42:12.899Z Has data issue: false hasContentIssue false
  • English
  • Français

Hereditary deficiency of the seventh component of complement and recurrent meningococcal infection: investigations of an Irish family using a novel haemolytic screening assay for complement activity and C7 M/N allotyping

Published online by Cambridge University Press:  15 May 2009

L. J. Egan ,
A. Orren ,
J. Doherty ,
R. Würzner  and
C. F. McCarthy
L. J. Egan
Affiliation:
Department of Medicine, Clinical Science Institute, University College Hospital, Galway, Ireland
A. Orren*
Affiliation:
Molecular Immunopathology Unit, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, England
J. Doherty
Affiliation:
Department of Medicine, Clinical Science Institute, University College Hospital, Galway, Ireland
R. Würzner
Affiliation:
Molecular Immunopathology Unit, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, England
C. F. McCarthy
Affiliation:
Department of Medicine, Clinical Science Institute, University College Hospital, Galway, Ireland
*
* Author for correspondence and present address: Dr A. Orren, Department of Immunology, University College Hospital, Galway, Ireland.
Rights & Permissions [Opens in a new window]

Summary

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Terminal complement component deficiency predisposes to meningococcal infection and is inherited in an autosomal co-dominant manner. An Irish family is described, in which 2 of 3 brothers had recurrent meningococcal infection. A novel screening assay was used to investigate for terminal complement deficiency and the 2 affected brothers were found to be completely deficient in the seventh component of complement (C7). Enzyme-linked immunosorbent assay for C7 revealed lower than normal levels in the remaining brother and parents. C7 M/N protein polymorphism allotyping, used to investigate the segregation of the C7 deficiency genes, showed that the apparently complement sufficient brother was heterozygous C7 deficient and a carrier of one of the deficiency genes. Complement screening should be carried out in any individual suffering recurrent meningococcal infection or infection with an uncommon meningococcal serogroup. Identification of complement deficient patients allows the implementation of strategies to prevent recurrent infection.

Type
Research Article
Information
Epidemiology & Infection , Volume 113 , Issue 2 , October 1994 , pp. 275 - 281
Copyright
Copyright © Cambridge University Press 1994

References

REFERENCES

1.Würzner, R, Orren, A, Lachmann, PJInherited deficiencies of the terminal components of human complement. Immunodef Rev 1992; 3: 123–47.Google ScholarPubMed
2.Hobart, MJ, Fernie, BA, DiScipio, RG, Lachmann, PJA physical map of the C6 and C7 complement component gene region on chromosome-5p13. Human Molec Genet 1993: 2: 1035–6.CrossRefGoogle ScholarPubMed
3.McBride, SJ, McCluskey, DR, Jackson, PTSelective C7 complement deficiency causing recurrent meningococcal infection. J Infect 1991; 22: 273–6.CrossRefGoogle ScholarPubMed
4.Hobart, MJ, Lachmann, PJAllotypes of complement components in man. Transplant Rev 1976; 32: 26–42.Google ScholarPubMed
5.Hobart, MJ, Joysey, V, Lachmann, PJInherited structural variation and linkage relationships of C7. J Immunogenet 1978: 5: 157–63.CrossRefGoogle ScholarPubMed
6.Würzner, R, Hobart, MJ, Orren, A et al. , A novel protein polymorphism of human complement C7 detected by a monoclonal antibody. Immunogenet 1992; 35: 398–402.CrossRefGoogle ScholarPubMed
7.Harrison, RA, Lachmann, PJ Complement technology. In: Weir, DM, ed. Handbook of experimental immunology, vol 1. Oxford: Blackwell Scientific Publications, 1986; 39.1–39, 49.Google Scholar
8.Würzner, R, Orren, A, Potter, P et al. , Functionally active complement proteins C6 and C7 detected in C6 and C7 deficient individuals. Clin Exp Immunol 1991; 83: 430–7.CrossRefGoogle ScholarPubMed
9.Würzner, R, Ranee, N, Potter, PC, Hendricks, ML, Lachmann, PJ, Orren, AThe C7 M/N protein polymorphism typing applied to inherited deficiencies of human complement proteins C6 and C7. Clin Exp Immunol 1992; 89: 485–9.CrossRefGoogle ScholarPubMed
10.Ross, SC, Denson, PComplement deficiency status and infection: epidemiology, pathogenesis and consequences of neisserial and other infections in an immune deficiency. Medicine 1984; 63: 243–73.CrossRefGoogle Scholar
11.Peterson, BH, Lee, TJ, Snyderman, R, Brooks, GFNeisseria meningitidis and Neisseria gonorrhoea bacteremia associated with C6, C7 or C8 deficiency. Ann Intern Med 1979: 90: 917–20.CrossRefGoogle Scholar
12.Corbett-Feeney, GAA change in meningococcal serogroups in the West of Ireland ? Ir J Med Sc 1991; 160: 134–6.CrossRefGoogle ScholarPubMed
13.Fijen, CAP, Kuijper, EJ, Hannema, AJ, Sjöholm, AG, Putten, JPMComplement deficiencies in patients over 10 years old with meningococcal disease due to uncommon serogroups. Lancet 1989; ii: 585–8.CrossRefGoogle Scholar
14.Ross, SC, Rosenthal, PJ, Berberich, HM, Denson, PKilling of Neisseria meningitidis by human neutrophils: implications for normal and complement deficient individuals. J Infect Dis 1987; 155: 1266–75.CrossRefGoogle ScholarPubMed
15.Lehner, PJ, Davies, KA, Walport, MJ et al. , Meningococcal septicaemia in a C6 deficient patient and effects of plasma transfusion on lipopolysaccharide release. Lancet 1992; 340: 1379–81.CrossRefGoogle Scholar
16.Potter, PC, Frasch, CE, van der Sande, WJM, Cooper, RC, Patel, Y, Orren, AProphylaxis against Neisseria meningitidis infections and antibody responses in patients with deficiency of the sixth component of complement. J Infect Dis 1990; 161: 932–7.CrossRefGoogle ScholarPubMed
17.Meningitis and Special Pathogens Branch, Division of Bacterial Diseases, Center for Infectious Diseases, CDC. Availability of meningococcal vaccine for in single dose vials for travellers and high risk persons. MMWR 1990; 39: 763.Google Scholar
18.Andreoni, J, Kayhty, H, Densen, PVaccination and the role of capsular polysaccharide antibody in prevention of recurrent meningococcal disease in late complement component deficient individuals. J Infect Dis 1993; 168: 227–31.CrossRefGoogle ScholarPubMed
19.Lifely, MR, Moreno, C, Lindon, JCAn integrated molecular and immunological approach towards a meningococcal group B vaccine. Vaccine 1987; 5: 11–26.CrossRefGoogle ScholarPubMed
20.Griffis, JMBactericidal activity of meningococcal antisera. Blocking by IgA of lytic antibody in human convalescent sera. J Immunol 1975; 114: 1779–84.CrossRefGoogle Scholar
21.Brai, M, Natoli, D, Misiano, G, Pecorano, V, D'Agostino, RHigh prevalence of C7/C8 deficiency among sporadic meningococcal disease patients in Sicily. Complement Inflamm 1989; 6: 316.Google Scholar
22.Zimran, A, Rudensky, B, Kramer, MR et al. , Hereditary complement deficiency in survivors of meningococcal disease: high prevalence of C7/C8 deficiency in Sephardic (Moroccan) Jews. Quart J Med 1987; 63: 349–58.Google ScholarPubMed