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. 1976 Jun;57(6):1635–1643. doi: 10.1172/JCI108434

Hereditary deficiency of the fifth component of complement in man. II. Biological properties of C5-deficient human serum.

S I Rosenfeld, J Baum, R T Steigbigel, J P Leddy
PMCID: PMC436823  PMID: 777027

Abstract

The first known human kindred with hereditary deficiency of the fifth component of complement (C5) was documented in the accompanying report. This study examines several biological properties of C5-deficient (C5D) human serum, particularly sera obtained from two C5D homozygotes. The proband, who has inactive systemic lupus erythematosus is completely lacking C5, while her healthy half-sister has 1-2% of normal levels. Both sera were severely impaired in their ability to generate chemotactic activity for normal human neutrophils upon incubation with aggregated human gamma-globulin or Escherichia coli endotoxin. This function was fully restored in the sibling's serum, and substantially improved in the proband's serum, by addition of highly purified human C5 to normal serum concentrations. Sera from eight family members who were apparently heterozygous for C5 deficiency gave normal chemotactic scores. The ability of C5D serum to opsonize Saccharomyces cerevisiae (baker's yeast) or Candida albicans for ingestion by normal neutrophils was completely normal. In addition, C5D serum was capable of promoting normal phagocytosis and intracellular killing of Staphylococcus aureus. The proband's serum was incapable of mediating lysis of erythrocytes from a patient with paroxysmal nocturnal hemoglobinuria in both the sucrose hemolysia and acid hemolysis tests, and also lacked bactericidal activity against sensitized or unsensitized Salmonella typhi. The sibling's serum, containing only 1-2% of normal C5, effectively lysed S. typhi, but only at eightfold lower serum dilutions as compared to normals. These findings underscore the critical role of C5 in the generation of chemotactic activity and in cytolytic reactions, as opposed to a nonobligatory or minimal role in opsonization, at least for the organisms under study.

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Selected References

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  1. Alper C. A., Rosen F. S. Genetic aspects of the complement system. Adv Immunol. 1971;14:251–290. doi: 10.1016/s0065-2776(08)60286-2. [DOI] [PubMed] [Google Scholar]
  2. Boyer J. T., Gall E. P., Norman M. E., Nilsson U. R., Zimmerman T. S. Hereditary deficiency of the seventh component of complement. J Clin Invest. 1975 Oct;56(4):905–913. doi: 10.1172/JCI108170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. CINADER B., DUBISKI S., WARDLAW A. C. DISTRIBUTION, INHERITANCE, AND PROPERTIES OF AN ANTIGEN, MUB1, AND ITS RELATION TO HEMOLYTIC COMPLEMENT. J Exp Med. 1964 Nov 1;120:897–924. doi: 10.1084/jem.120.5.897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Caren L. D., Rosenberg L. T. The role of complement in resistance to endogenous and exogenous infection with a common mouse pathogen, Corynebacterium kutscheri. J Exp Med. 1966 Oct 1;124(4):689–699. doi: 10.1084/jem.124.4.689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cooper N. R., Müller-Eberhard H. J. The reaction mechanism of human C5 in immune hemolysis. J Exp Med. 1970 Oct 1;132(4):775–793. doi: 10.1084/jem.132.4.775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gallin J. I., Clark R. A., Frank M. M. Kinetic analysis of chemotactic factor generation in human serum via activation of the classical and alternate complement pathways. Clin Immunol Immunopathol. 1975 Jan;3(3):334–346. doi: 10.1016/0090-1229(75)90020-3. [DOI] [PubMed] [Google Scholar]
  7. Götze O., Müller-Eberhard H. J. The C3-activator system: an alternate pathway of complement activation. J Exp Med. 1971 Sep 1;134(3 Pt 2):90s–108s. [PubMed] [Google Scholar]
  8. Jacobs J. C., Miller M. E. Fatal familial Leiner's disease: a deficiency of the opsonic activity of serum complement. Pediatrics. 1972 Feb;49(2):225–232. [PubMed] [Google Scholar]
  9. Kolb W. P., Muller-Eberhard H. J. The membrane attack mechanism of complement. Isolation and subunit composition of the C5b-9 complex. J Exp Med. 1975 Apr 1;141(4):724–735. [PMC free article] [PubMed] [Google Scholar]
  10. Lachmann P. J., Kay A. B., Thompson R. A. The chemotactic activity for neutrophil and eosinophil leucocytes of the trimolecular complex of the fifth, sixth and seventh components of human complement (C567) prepared in free solution by the 'reactive lysis' procedure. Immunology. 1970 Dec;19(6):895–899. [PMC free article] [PubMed] [Google Scholar]
  11. Leddy J. P., Frank M. M., Gaither T., Baum J., Klemperer M. R. Hereditary deficiency of the sixth component of complement in man. I. Immunochemical, biologic, and family studies. J Clin Invest. 1974 Feb;53(2):544–553. doi: 10.1172/JCI107588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lehrer R. I., Cline M. J. Interaction of Candida albicans with human leukocytes and serum. J Bacteriol. 1969 Jun;98(3):996–1004. doi: 10.1128/jb.98.3.996-1004.1969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Miller M. E., Nilsson U. R. A familial deficiency of the phagocytosis-enhancing activity of serum related to a dysfunction of the fifth component of complement (C5). N Engl J Med. 1970 Feb 12;282(7):354–358. doi: 10.1056/NEJM197002122820702. [DOI] [PubMed] [Google Scholar]
  14. Miller M. E., Nilsson U. R. A major role of the fifth component of complement (C5) in the opsonization of yeast particles. Partial dichotomy of function and immunochemical measurement. Clin Immunol Immunopathol. 1974 Jan;2(2):246–255. doi: 10.1016/0090-1229(74)90042-7. [DOI] [PubMed] [Google Scholar]
  15. Morelli R., Rosenberg L. T. Role of complement during experimental Candida infection in mice. Infect Immun. 1971 Apr;3(4):521–523. doi: 10.1128/iai.3.4.521-523.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Morelli R., Rosenberg L. T. The role of complement in the phagocytosis of Candida albicans by mouse peripheral blood leukocytes. J Immunol. 1971 Aug;107(2):476–480. [PubMed] [Google Scholar]
  17. Mowat A. G., Baum J. Chemotaxis of polymorphonuclear leukocytes from patients with rheumatoid arthritis. J Clin Invest. 1971 Dec;50(12):2541–2549. doi: 10.1172/JCI106754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nilsson U. R., Miller M. E., Wyman S. A functional abnormality of the fifth component of complement (C5) from human serum of individuals with a familial opsonic defect. J Immunol. 1974 Mar;112(3):1164–1176. [PubMed] [Google Scholar]
  19. Nilsson U. R., Müller-Eberhard H. J. Deficiency of the fifth component of complement in mice with an inherited complement defect. J Exp Med. 1967 Jan 1;125(1):1–16. doi: 10.1084/jem.125.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nilsson U. R., Tomar R. H., Taylor F. B., Jr Additional studies on human C5: development of a modified purification method and characterization of the purified product by polyacrylamide gel electrophoresis. Immunochemistry. 1972 Jul;9(7):709–723. doi: 10.1016/0019-2791(72)90015-8. [DOI] [PubMed] [Google Scholar]
  21. Root R. K., Ellman L., Frank M. M. Bactericidal and opsonic properties of C4-deficient guinea pig serum. J Immunol. 1972 Sep;109(3):477–486. [PubMed] [Google Scholar]
  22. Rosenfeld S. I., Kelly M. E., Leddy J. P. Hereditary deficiency of the fifth component of complement in man. I. Clinical, immunochemical, and family studies. J Clin Invest. 1976 Jun;57(6):1626–1634. doi: 10.1172/JCI108433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shin H. S., Smith M. R., Wood W. B., Jr Heat labile opsonins to pneumococcus. II. Involvement of C3 and C5. J Exp Med. 1969 Dec 1;130(6):1229–1241. doi: 10.1084/jem.130.6.1229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Snyderman R., Phillips J. K., Mergenhagen S. E. Biological activity of complement in vivo. Role of C5 in the accumulation of polymorphonuclear leukocytes in inflammatory exudates. J Exp Med. 1971 Nov 1;134(5):1131–1143. doi: 10.1084/jem.134.5.1131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Snyderman R., Phillips J., Mergenhagen S. E. Polymorphonuclear leukocyte chemotactic activity in rabbit serum and Guinea pig serum treated with immune complexes: evidence for c5a as the major chemotactic factor. Infect Immun. 1970 Jun;1(6):521–525. doi: 10.1128/iai.1.6.521-525.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Solberg C. O., Hellum K. B. Influence of serum on the bactericidal activity of neutrophil granulocytes. Acta Pathol Microbiol Scand B Microbiol Immunol. 1973 Oct;81(5):621–626. doi: 10.1111/j.1699-0463.1973.tb02252.x. [DOI] [PubMed] [Google Scholar]
  27. Steigbigel R. T., Lambert L. H., Jr, Remington J. S. Phagocytic and bacterial properties of normal human monocytes. J Clin Invest. 1974 Jan;53(1):131–142. doi: 10.1172/JCI107531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tachibana D. K., Hayflick L., Rosenberg L. T. Effect of complete and genetically defective mouse complement on Mycoplasma canis. J Infect Dis. 1970 May;121(5):541–544. doi: 10.1093/infdis/121.5.541. [DOI] [PubMed] [Google Scholar]
  29. WARD P. A., COCHRANE C. G., MUELLER-EBERHARD H. J. THE ROLE OF SERUM COMPLEMENT IN CHEMOTAXIS OF LEUKOCYTES IN VITRO. J Exp Med. 1965 Aug 1;122:327–346. doi: 10.1084/jem.122.2.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ward P. A., Lepow I. H., Newman L. J. Bacterial factors chemotactic for polymorphonuclear leukocytes. Am J Pathol. 1968 Apr;52(4):725–736. [PMC free article] [PubMed] [Google Scholar]
  31. Ward P. A., Newman L. J. A neutrophil chemotactic factor from human C'5. J Immunol. 1969 Jan;102(1):93–99. [PubMed] [Google Scholar]
  32. Wellek B., Opferkuch W. A case of deficiency of the seventh component of complement in man. Biological properties of a C7-deficient serum and description of a C7-inactivating principle. Clin Exp Immunol. 1975 Feb;19(2):223–235. [PMC free article] [PubMed] [Google Scholar]

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