Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1976 Jan;57(1):222–229. doi: 10.1172/JCI108263

Homozygous human C3 deficiency. The role of C3 in antibody production, C-1s-induced vasopermeability, and cobra venom-induced passive hemolysis.

C A Alper, H R Colten, J S Gear, A R Rabson, F S Rosen
PMCID: PMC436642  PMID: 1107355

Abstract

Studies of the family of a patient with marked deficiency of the third component of complement (C3) demonstrated that the patient was homozygous for a blank allele at the C3 locus, C3-. Metabolic studies with purified radiolabeled C3 in the patient revealed a mildly elevated fractional catabolic rate and a markedly reduced synthesis rate, consistent with a lack of C3 synthesis as the patient's primary defect. There was also a mild increase in the rate of conversion of purified C3 added to her serum and incubated at 37 degrees C in vitro. Major blood group-compatible erythrocytes from a patient with paroxysmal nocturnal hemoglobinuria had the same shortened survival in the C3-deficient patient as in a normal control. Although no leukocytosis developed in the patient in spontaneous infection by pyogenic organisms, there was a normal leukocytosis in response to the injection of thyphoid vaccine. The intradermal injection of C-1s, which produces a marked increase in vasopermeability in the skin of normal subjects, produced no definite change in the patient, possibly implicating C3 or a protein in the alternative pathway as the normal mediator of this response. The patient's serum exhibited near-normal immune adherence activity, confirming the lack of requirement of C3 for this function. C5 inactivation and passive hemolysis of unsensitized guinea pig erythrocytes occurred normally in C3-deficient serum on incubation with cobra venom factor, indicating that C3 is not required for these reactions. The patient's humoral antibody response to both protein and carbohydrate antigens was entirely normal, making it unlikely that C3 is required for antigen processing.

Full text

PDF
222

Images in this article

225Image
on p.225
225Image
on p.225

Selected References

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

  1. Abramson N., Alper C. A., Lachmann P. J., Rosen F. S., Jandl J. H. Deficiency of C3 inactivator in man. J Immunol. 1971 Jul;107(1):19–27. [PubMed] [Google Scholar]
  2. Alper C. A., Bloch K. J., Rosen F. S. Increased susceptibility to infection in a patient with type II essential hypercatabolism of C3. N Engl J Med. 1973 Mar 22;288(12):601–606. doi: 10.1056/NEJM197303222881204. [DOI] [PubMed] [Google Scholar]
  3. Alper C. A., Colten H. R., Rosen F. S., Rabson A. R., Macnab G. M., Gear J. S. Homozygous deficiency of C3 in a patient with repeated infections. Lancet. 1972 Dec 2;2(7788):1179–1181. doi: 10.1016/s0140-6736(72)92598-6. [DOI] [PubMed] [Google Scholar]
  4. Alper C. A., Propp R. P. Genetic polymorphism of the third component of human complement (C'3). J Clin Invest. 1968 Sep;47(9):2181–2191. doi: 10.1172/JCI105904. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Alper C. A., Propp R. P., Klemperer M. R., Rosen F. S. Inherited deficiency of the third component of human complement (C'3). J Clin Invest. 1969 Mar;48(3):553–557. doi: 10.1172/JCI106013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Alper C. A., Rosen F. S. Alper CA, Rosen FS: Studies of the in vivo behavior of human C'3 in normal subjects and patients. J Clin Invest. 1967 Dec;46(12):2021–2034. doi: 10.1172/JCI105691. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ballow M., Cochrane C. G. Two anticomplementary factors in cobra venom: hemolysis of guinea pig erythrocytes by one of them. J Immunol. 1969 Nov;103(5):944–952. [PubMed] [Google Scholar]
  8. Bitter-Suermann D., Dierich M., König W., Hadding U. Bypass-activation of the complement system starting with C3. I. Generation and function of an enzyme from a factor of guinea-pig serum and cobra venom. Immunology. 1972 Sep;23(3):267–281. [PMC free article] [PubMed] [Google Scholar]
  9. Cooper N. R. Immune adherence by the fourth component of complement. Science. 1969 Jul 25;165(3891):396–398. doi: 10.1126/science.165.3891.396. [DOI] [PubMed] [Google Scholar]
  10. Dias Da Silva W., Lepow I. H. Complement as a mediator of inflammation. II. Biological properties of anaphylatoxin prepared with purified components of human complement. J Exp Med. 1967 May 1;125(5):921–946. doi: 10.1084/jem.125.5.921. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. GRAY S. J., STERLING K. The tagging of red cells and plasma proteins with radioactive chromium. J Clin Invest. 1950 Dec;29(12):1604–1613. doi: 10.1172/JCI102403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Götze O., Müller-Eberhard H. J. Paroxysmal nocturnal hemoglobinuria. Hemolysis initiated by the C3 activator system. N Engl J Med. 1972 Jan 27;286(4):180–184. doi: 10.1056/NEJM197201272860403. [DOI] [PubMed] [Google Scholar]
  13. HAINES A. L., LEPOW I. H. STUDIES ON HUMAN C'1-ESTERASE. II. FUNCTION OF PURIFIED C'1-ESTERASE IN THE HUMAN COMPLEMENT SYSTEM. J Immunol. 1964 Mar;92:468–478. [PubMed] [Google Scholar]
  14. HINZ C. F., Jr, JORDAN W. S., Jr, PILLEMER L. The properdin system and immunity. IV. The hemolysis of erythrocytes from patients with paroxysmal nocturnal hemoglobinuria. J Clin Invest. 1956 May;35(5):453–457. doi: 10.1172/JCI103296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jensen J. Anaphylatoxin in its relation to the complement system. Science. 1967 Mar 3;155(3766):1122–1123. doi: 10.1126/science.155.3766.1122. [DOI] [PubMed] [Google Scholar]
  16. Jondal M., Holm G., Wigzell H. Surface markers on human T and B lymphocytes. I. A large population of lymphocytes forming nonimmune rosettes with sheep red blood cells. J Exp Med. 1972 Aug 1;136(2):207–215. doi: 10.1084/jem.136.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. KAN S. Y., GARDNER F. H. LIFE SPAN OF RETICULOCYTES IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA. Blood. 1965 May;25:759–766. [PubMed] [Google Scholar]
  18. Klein P. G., Wellensiek H. J. Multiple nature of the third component of guinea-pig complement. I. Separation and characterization of three factors a, b, and c, essential for haemolysis. Immunology. 1965 Jun;8(6):590–603. [PMC free article] [PubMed] [Google Scholar]
  19. Klemperer M. R., Donaldson V. H., Rosen F. S. Effect of C'1 esterase on vascular permeability in man: studies in normal and complement-deficient individuals and in patients with hereditary angioneurotic edema. J Clin Invest. 1968 Mar;47(3):604–611. doi: 10.1172/JCI105756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lachmann P. J., Nicol P. Reaction mechanism of the alternative pathway of complement fixation. Lancet. 1973 Mar 3;1(7801):465–467. doi: 10.1016/s0140-6736(73)91886-2. [DOI] [PubMed] [Google Scholar]
  21. Laurell C. B. Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem. 1966 Apr;15(1):45–52. doi: 10.1016/0003-2697(66)90246-6. [DOI] [PubMed] [Google Scholar]
  22. MATTHEWS C. M. The theory of tracer experiments with 131I-labelled plasma proteins. Phys Med Biol. 1957 Jul;2(1):36–53. doi: 10.1088/0031-9155/2/1/305. [DOI] [PubMed] [Google Scholar]
  23. Muller-Eberhard H. J., Nilsson U. R., Dalmasso A. P., Polley M. J., Calcott M. A. A molecular concept of immune cytolysis. Arch Pathol. 1966 Sep;82(3):205–217. [PubMed] [Google Scholar]
  24. NELSON R. A., Jr The immune-adherence phenomenon; an immunologically specific reaction between microorganisms and erythrocytes leading to enhanced phagocytosis. Science. 1953 Dec 18;118(3077):733–737. doi: 10.1126/science.118.3077.733. [DOI] [PubMed] [Google Scholar]
  25. NILSSON U. R., MUELLER-EBERHARD H. J. ISOLATION OF BETA IF-GLOBULIN FROM HUMAN SERUM AND ITS CHARACTERIZATION AS THE FIFTH COMPONENT OF COMPLEMENT. J Exp Med. 1965 Aug 1;122:277–298. doi: 10.1084/jem.122.2.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Nelson R. A., Jr A new concept of immunosuppression in hypersensitivity reactions and in transplantation immunity. Surv Ophthalmol. 1966 Aug;11(4):498–505. [PubMed] [Google Scholar]
  27. Pepys M. B. Role of complement in induction of antibody production in vivo. Effect of cobra factor and other C3-reactive agents on thymus-dependent and thymus-independent antibody responses. J Exp Med. 1974 Jul 1;140(1):126–145. doi: 10.1084/jem.140.1.126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pickering R. J., Wolfson M. R., Good R. A., Gewurz H. Passive hemolysis by serum and cobra venom factor: a new mechanism inducing membrane damage by complement. Proc Natl Acad Sci U S A. 1969 Feb;62(2):521–527. doi: 10.1073/pnas.62.2.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rother K. Leucocyte mobilizing factor: a new biological activity derived from the third component of complement. Eur J Immunol. 1972 Dec;2(6):550–558. doi: 10.1002/eji.1830020615. [DOI] [PubMed] [Google Scholar]
  30. Willms K., Rosen F. S., Donaldson V. H. Observations on the ultrastructure of lesions induced in human and guinea pig skin by C 1 esterase and polypeptide from hereditary angioneurotic edema (HANE) plasma. Clin Immunol Immunopathol. 1975 Jul;4(2):174–188. doi: 10.1016/0090-1229(75)90053-7. [DOI] [PubMed] [Google Scholar]
  31. YACHNIN S. THE HEMOLYSIS OF RED CELLS FROM PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA BY PARTIALLY PURIFIED SUB-COMPONENTS OF THE THIRD COMPLEMENT COMPONENT. J Clin Invest. 1965 Sep;44:1534–1546. doi: 10.1172/JCI105260. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES