Inherited Deficiency of the Seventh Component of Complement Associated with Nephritis. Propensity to Formation of C56 and Related C7-consuming Activity

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1978 Jun 1

PMID 350902

Citations 5

Authors

G R Nemerow

H Gewurz

S G Osofsky

T F Lint

Affiliations

Soon will be listed here.

Abstract

A 46-yr-old female with chronic pyelonephritis was found to lack complement (C) activity by the use of hemolytic screen assays in agarose gels. These assays also revealed a propensity of patient serum to form an activated complex of the fifth and sixth components of C, C56. Each of the C component hemolytic activities was present in normal or elevated amounts with the exception of C7, which was undetectable; addition of purified C7 led to the restoration of hemolytic activity. C-dependent phagocytosis, immune adherence, and neutrophil chemotaxis were normal. Family studies demonstrated that the defect was transmitted as an autosomal codominant apparently not linked with alleles at the HLA-A or HLA-B loci. Persisting C56 was readily formed in this as compared to normal serum upon incubation with multiple C activators including zymosan, inulin, immune complexes, heat-aggregated human gamma globulin, endotoxin, and agarose. A heat-stable (56 degrees C, 30 min) activity which consumed C7 with time-and temperature-dependent kinetics was detected in plasma and serum, and seemed to be similar to a "C7 inactivator" previously described in another C7-deficient individual. However, this activity was found to have properties identical to those of C56 during low ionic strength precipitation and chromatography on Sephadex G-200, to be specifically removed upon passage through an anti-C5 immunoadsorbent column, and to be associated with a small amount of C56, suggesting that it represents an expression of small amounts of C56 rather than a new C-inhibitory activity. Thus, an individual with chronic nephritis lacking C7 is reported; the utility of a hemolytic screen assay in agarose plates for the detection of such patients is emphasized; persisting C56 is shown readily to be formed in this serum; and the presence of C7-consuming activity which is associated with and in all likelihood attributable to C56 is shown.

Citing Articles

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Efficacy of HIV-specific and 'antibody-independent' mechanisms for complement activation by HIV-infected cells.

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Inherited deficiency of C8 in a patient with recurrent meningococcal infections: further evidence for a dysfunctional C8 molecule and nonlinkage to the HLA system.

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Familial deficiency of the seventh component of complement associated with recurrent meningococcal infections.

Nurnberger W, Pietsch H, Seger R, Bufon T, Wahn V Eur J Pediatr. 1989; 148(8):758-60.

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Combined total deficiency of C7 and C4B with systemic lupus erythematosus (SLE).

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PMID: 1347491 PMC: 1554335. DOI: 10.1111/j.1365-2249.1992.tb03011.x.

References

Nishioka K . Measurements of complement by agglutination of human erythrocytes reacting in immune-adherence. J Immunol. 1963; 90:86-97. View

Leddy J, Frank M, Gaither T, Baum J, KLEMPERER M . Hereditary deficiency of the sixth component of complement in man. I. Immunochemical, biologic, and family studies. J Clin Invest. 1974; 53(2):544-53. PMC: 301497. DOI: 10.1172/JCI107588. View

Delage J, Bergeron P, Simard J, Prochazka E . Hereditary C7 deficiency. Diagnosis and HLA studies in a French-Canadian family. J Clin Invest. 1977; 60(5):1061-9. PMC: 372458. DOI: 10.1172/JCI108857. View

Gewurz A, Lint T, Roberts J, Zeitz H, Gewurz H . Homozygous C2 deficiency with fulminant lupus erythematosus: severe nephritis via the alternative complement pathway. Arthritis Rheum. 1978; 21(1):28-36. DOI: 10.1002/art.1780210106. View

Thompson R, LACHMANN P . A second case of human C3b inhibitor (KAF) deficiency. Clin Exp Immunol. 1977; 27(1):23-9. PMC: 1540911. View

Baker P, Lint T, Mortensen R, Gewurz H . C567-initiated cytolysis of lymphoid cells: description of the phenomenon and studies on its control by C567 inhibitors. J Immunol. 1977; 118(1):198-202. View

Baker P, Rubin L, Lint T, McLeod B, Gewurz H . Binding of the complement intermediate C56 to zymosan in acute phase human sera. Clin Exp Immunol. 1975; 20(1):113-24. PMC: 1538180. View

Alper C, Colten H, Rosen F, Rabson A, MACNAB G, Gear J . Homozygous deficiency of C3 in a patient with repeated infections. Lancet. 1972; 2(7788):1179-81. DOI: 10.1016/s0140-6736(72)92598-6. View

Thompson R, Rowe D . Reactive haemolysis--a distinctive form of red cell lysis. Immunology. 1968; 14(5):745-62. PMC: 1409402. View

10.

LACHMANN P, Thompson R . Reactive lysis: the complement-mediated lysis of unsensitized cells. II. The characterization of activated reactor as C56 and the participation of C8 and C9. J Exp Med. 1970; 131(4):643-57. PMC: 2138770. DOI: 10.1084/jem.131.4.643. View

11.

Goldlust M, Shin H, HAMMER C, Mayer M . Studies of complement complex C5b,6 eluted from--EAC-6: reaction of C5b,6 with EAC4b,3b and evidence on the role of C2a and C3b in the activation of C5. J Immunol. 1974; 113(3):998-1007. View

12.

Nilsson U, Miller M, 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; 112(3):1164-76. View

13.

Goldman J, Austen K . Reaction mechanisms of nascent C567 (reactive lysis). II. Killing of a rough form of Escherichia coli by C567, C8, and C9. J Infect Dis. 1974; 129(4):444-50. DOI: 10.1093/infdis/129.4.444. View

14.

Abramson N, Alper C, LACHMANN P, Rosen F, JANDL J . Deficiency of C3 inactivator in man. J Immunol. 1971; 107(1):19-27. View

15.

Petersen B, Graham J, Brooks G . Human deficiency of the eighth component of complement. The requirement of C8 for serum Neisseria gonorrhoeae bactericidal activity. J Clin Invest. 1976; 57(2):283-90. PMC: 436652. DOI: 10.1172/JCI108279. View

16.

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; 19(2):223-35. PMC: 1538101. View

17.

Lim D, Gewurz A, Lint T, Ghaze M, Sepheri B, Gewurz H . Absence of the sixth component of complement in a patient with repeated episodes of meningococcal meningitis. J Pediatr. 1976; 89(1):42-7. DOI: 10.1016/s0022-3476(76)80924-9. View

18.

Kitamura H, Matsumoto M, Inai S . Necessity of the divalent cation in the reaction between EAC1-8hu and C9gp. Int Arch Allergy Appl Immunol. 1976; 51(2):265-71. DOI: 10.1159/000231599. View

19.

Boyer J, Gall E, Norman M, Nilsson U, ZIMMERMAN T . Hereditary deficiency of the seventh component of complement. J Clin Invest. 1975; 56(4):905-13. PMC: 301946. DOI: 10.1172/JCI108170. View

20.

Alper C, Colten H, Gear J, Rabson A, Rosen F . Homozygous human C3 deficiency. The role of C3 in antibody production, C-1s-induced vasopermeability, and cobra venom-induced passive hemolysis. J Clin Invest. 1976; 57(1):222-9. PMC: 436642. DOI: 10.1172/JCI108263. View