Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1990 Sep;81(3):423–427. doi: 10.1111/j.1365-2249.1990.tb05350.x

Prevalence of hereditary properdin, C7 and C8 deficiencies in patients with meningococcal infections.

M Schlesinger 1, Z Nave 1, Y Levy 1, P E Slater 1, Z Fishelson 1
PMCID: PMC1534994  PMID: 2397612

Abstract

High incidence of hereditary complement (C) deficiencies was found among 101 patients who had a meningococcal disease. This study revealed 11 non-related patients with complete C deficiency: five deficient in C7, three in C8, two in properdin and one in C2. Additional C-deficient individuals, most of them with no history of severe bacterial infections, were detected in family studies. The C8-deficient patients were found to have a selective deficiency of the C8-beta subunit and a reduced expression of the alpha/gamma subunit. Only a few families with properdin deficiency have been described so far. However, it is likely that frequent analysis of the activity of the alternative C pathway in survivors of severe bacterial infections will disclose numerous properdin-deficient patients. All our C7-, C8- and properdin-deficient patients are Sephardic Jews whose families originated from Morocco, Yemen (C7 and C8 deficient) or Tunisia (properdin deficient). This and other findings indicate that the type of complement abnormality found in association with meningococcal infections varies with the ethnic origin of the patient.

Full text

PDF
423

Images in this article

424Fig. 1
on p.424
425Fig. 2
on p.425

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Densen P., Weiler J. M., Griffiss J. M., Hoffmann L. G. Familial properdin deficiency and fatal meningococcemia. Correction of the bactericidal defect by vaccination. N Engl J Med. 1987 Apr 9;316(15):922–926. doi: 10.1056/NEJM198704093161506. [DOI] [PubMed] [Google Scholar]
  2. Fijen C. A., Kuijper E. J., Hannema A. J., Sjöholm A. G., van Putten J. P. Complement deficiencies in patients over ten years old with meningococcal disease due to uncommon serogroups. Lancet. 1989 Sep 9;2(8663):585–588. doi: 10.1016/s0140-6736(89)90712-5. [DOI] [PubMed] [Google Scholar]
  3. Gelfand E. W., Rao C. P., Minta J. O., Ham T., Purkall D. B., Ruddy S. Inherited deficiency of properdin and C2 in a patient with recurrent bacteremia. Am J Med. 1987 Mar 23;82(3 Spec No):671–675. doi: 10.1016/0002-9343(87)90122-7. [DOI] [PubMed] [Google Scholar]
  4. Goonewardena P., Sjöholm A. G., Nilsson L. A., Pettersson U. Linkage analysis of the properdin deficiency gene: suggestion of a locus in the proximal part of the short arm of the X chromosome. Genomics. 1988 Feb;2(2):115–118. doi: 10.1016/0888-7543(88)90092-4. [DOI] [PubMed] [Google Scholar]
  5. Goundis D., Holt S. M., Boyd Y., Reid K. B. Localization of the properdin structural locus to Xp11.23-Xp21.1. Genomics. 1989 Jul;5(1):56–60. doi: 10.1016/0888-7543(89)90085-2. [DOI] [PubMed] [Google Scholar]
  6. Hauptmann G. Frequency of complement deficiencies in man, disease associations and chromosome assignment of complement genes and linkage groups. A summary of the data from the literature. Complement Inflamm. 1989;6(2):74–80. doi: 10.1159/000463077. [DOI] [PubMed] [Google Scholar]
  7. Inaba S., Okochi K., Fukada K., Kinoshita S., Maeda Y., Yoshinari M. The occurrence of precipitating antibodies in transfused Japanese patients with hereditary ninth component of complement deficiency and frequency of C9 deficiency. Transfusion. 1987 Nov-Dec;27(6):475–477. doi: 10.1046/j.1537-2995.1987.27688071698.x. [DOI] [PubMed] [Google Scholar]
  8. Inai S., Akagaki Y., Moriyama T., Fukumori Y., Yoshimura K., Ohnoki S., Yamaguchi H. Inherited deficiencies of the late-acting complement components other than C9 found among healthy blood donors. Int Arch Allergy Appl Immunol. 1989;90(3):274–279. doi: 10.1159/000235037. [DOI] [PubMed] [Google Scholar]
  9. Klob W. P., Müller-Eberhard H. J. The membrane attack mechanism of complement: the three polypeptide chain structure of the eigth component (C8). J Exp Med. 1976 May 1;143(5):1131–1139. doi: 10.1084/jem.143.5.1131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  11. Mancini G., Carbonara A. O., Heremans J. F. Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry. 1965 Sep;2(3):235–254. doi: 10.1016/0019-2791(65)90004-2. [DOI] [PubMed] [Google Scholar]
  12. Medicus R. G., Esser A. F., Fernandez H. N., Müller-Eberhard H. J. Native and activated properdin: interconvertibility and identity of amino- and carboxy-terminal sequences. J Immunol. 1980 Feb;124(2):602–606. [PubMed] [Google Scholar]
  13. Nagata M., Hara T., Aoki T., Mizuno Y., Akeda H., Inaba S., Tsumoto K., Ueda K. Inherited deficiency of ninth component of complement: an increased risk of meningococcal meningitis. J Pediatr. 1989 Feb;114(2):260–264. doi: 10.1016/s0022-3476(89)80793-0. [DOI] [PubMed] [Google Scholar]
  14. Nielsen H. E., Koch C. Congenital properdin deficiency and meningococcal infection. Clin Immunol Immunopathol. 1987 Aug;44(2):134–139. doi: 10.1016/0090-1229(87)90060-2. [DOI] [PubMed] [Google Scholar]
  15. Nürnberger W., Pietsch H., Willers R., Bufon T., Hänsch G. M., Seger R., Rodriguez-Valverde V., Schroten H., Hershko C., Tedesco F. Deficiency of the eighth component of complement. Evidence for linkage of C8 alpha-gamma pattern with C8 beta deficiency in sera of twelve patients. Scand J Immunol. 1989 Jul;30(1):45–49. doi: 10.1111/j.1365-3083.1989.tb01187.x. [DOI] [PubMed] [Google Scholar]
  16. Orren A., Potter P. C., Cooper R. C., du Toit E. Deficiency of the sixth component of complement and susceptibility to Neisseria meningitidis infections: studies in 10 families and five isolated cases. Immunology. 1987 Oct;62(2):249–253. [PMC free article] [PubMed] [Google Scholar]
  17. Platts-Mills T. A., Ishizaka K. Activation of the alternate pathway of human complements by rabbit cells. J Immunol. 1974 Jul;113(1):348–358. [PubMed] [Google Scholar]
  18. Rittner C., Hargesheimer W., Stradmann B., Bertrams J., Baur M. P., Petersen B. H. Human C81 (alpha-gamma) polymorphism: detection in the alpha-gamma subunit on SDS-PAGE, formal genetics and linkage relationship. Am J Hum Genet. 1986 Apr;38(4):482–491. [PMC free article] [PubMed] [Google Scholar]
  19. Rogde S., Olaisen B., Gedde-Dahl T., Jr, Teisberg P. The C8A and C8B loci are closely linked on chromosome 1. Ann Hum Genet. 1986 May;50(Pt 2):139–144. doi: 10.1111/j.1469-1809.1986.tb01032.x. [DOI] [PubMed] [Google Scholar]
  20. Ross S. C., Densen P. Complement deficiency states and infection: epidemiology, pathogenesis and consequences of neisserial and other infections in an immune deficiency. Medicine (Baltimore) 1984 Sep;63(5):243–273. [PubMed] [Google Scholar]
  21. Rother K. Summary of reported deficiencies. Prog Allergy. 1986;39:202–211. [PubMed] [Google Scholar]
  22. Schreiber R. D., Morrison D. C., Podack E. R., Müller-Eberhard H. J. Bactericidal activity of the alternative complement pathway generated from 11 isolated plasma proteins. J Exp Med. 1979 Apr 1;149(4):870–882. doi: 10.1084/jem.149.4.870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schreiber R. D., Müller-Eberhard H. J. Assembly of the cytolytic alternative pathway of complement from 11 isolated plasma proteins. J Exp Med. 1978 Dec 1;148(6):1722–1727. doi: 10.1084/jem.148.6.1722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sjöholm A. G., Braconier J. H., Söderström C. Properdin deficiency in a family with fulminant meningococcal infections. Clin Exp Immunol. 1982 Nov;50(2):291–297. [PMC free article] [PubMed] [Google Scholar]
  25. Sjöholm A. G., Kuijper E. J., Tijssen C. C., Jansz A., Bol P., Spanjaard L., Zanen H. C. Dysfunctional properdin in a Dutch family with meningococcal disease. N Engl J Med. 1988 Jul 7;319(1):33–37. doi: 10.1056/NEJM198807073190106. [DOI] [PubMed] [Google Scholar]
  26. Söderström C., Braconier J. H., Käyhty H., Sjöholm A. G., Thuresson B. Immune response to tetravalent meningococcal vaccine: opsonic and bactericidal functions of normal and properdin deficient sera. Eur J Clin Microbiol Infect Dis. 1989 Mar;8(3):220–224. doi: 10.1007/BF01965264. [DOI] [PubMed] [Google Scholar]
  27. Tedesco F. Component deficiencies. 8. The eighth component. Prog Allergy. 1986;39:295–306. [PubMed] [Google Scholar]
  28. Torisu M., Sonozaki H., Inai S., Arata M. Deficiency of the fourth component of complement in man. J Immunol. 1970 Mar;104(3):728–737. [PubMed] [Google Scholar]
  29. Towbin H., Staehelin T., Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350–4354. doi: 10.1073/pnas.76.9.4350. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Zimran A., Rudensky B., Kramer M. R., Tedesco F., Ehrenfeld M., Raz R., Greif Z., Gelber M., Lishner M., Golan E. Hereditary complement deficiency in survivors of meningococcal disease: high prevalence of C7/C8 deficiency in Sephardic (Moroccan) Jews. Q J Med. 1987 Apr;63(240):349–358. [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES