Hereditary deficiency of the seventh component of complement.

Abstract

A B S T R A C T Deficiency of the seventh component of complement has been found in the serum of a 42-yr-old Caucasian woman who has Raynaud's phenomenon, sclerodactyly, and telangiectasia. Partial deficiency was found in the serum of the patient's parents and children, indicating a pattern of inheritance of autosomal codominance. Transfusion experiments indicated that exogenous C7 had a 91-h half-life in the patient. There was no evidence for C7 synthesis after transfusion. No C7 inhibitors were detected in the patient's serum. The patient's serum was found to support the activation of complement by both the classical and properdin pathways to the C7 stage. The addition of C7 to the patient's serum permitted it to support hemolytic reactions initiated by either pathway. No defects could be detected in plasma or whole blood coagulation. The patient's serum was deficient in opsonizing unsensitized yeast particles in serum and in the generation of chemotactic factor by antigen-antibody complexes and endotoxin. Both deficiencies were corrected by the addition of C7. These observations suggest a key role for C7 for in vitro yeast phagocytosis and chemotaxis generation. However, the patient's lack of infections indicates a relatively minor role for C7 in human resistance to infection.

Inherited Deficiency of the Seventh Component of Complement Associated with Nephritis

“…However, evidence presented in the investigations of two other C7-deficient individuals (16,29) clearly showed a lack of linkage between HLA and C7, as clo recent studies on C7 polymorphism in man (30). C7 deficiency was first reported in an individual with sclerodactyly and telangiectasia (13), and then later in an apparently normal adolescent (14), a 44-yrold lady with ankylosing spondylitis (16), in several members of a family who have shown an unusual predisposition to gonococcal infections (11), and in a 28-yr-old lady (G. S.) with systemic lupus erythematosus. Although there is no proof that the C7 deficiency was causally related to the symptoms observed in these individuals or in the patient described above, the present experience does extend the group of diseases with which patients with deficiency of C7 and thus, of the terminal complement components present.…”

“…One was a 42-yrold womian with Raynaud's phenomenon, sclerodactyly, and telangiectasia (13); a second was a healthy 12-yrold boy (14,15); and a third was a 44-yr-old woman (with two healthy homozygous siblings) with ankylosing spondylitis (16). In addition, a family with three members lacking C7 has recently been presented in 'Abbreviations used in this paper: BSA, bovine serum albumin, C, complement; EA, antibody-sensitized sheep erythrocytes; GGVB, GVB diluted with an equal volume of 5% glucose; GVB, veronal-buffered saline containing 0.1% gelatin; HLA, human leukocyte antigens; C7D, C7-deficient; C3B-INA, C3b-inactivator; C567-INH, C567-inhibitors.…”

A pedigree of deficiency of the ninth component of complement (C9)

“…Hereditary defects of complement components reported thus far mostly involved the classical pathway in human, including Clr (Pickering et al, 1971), Cls (Pondman et al, 1968), C4 (Hauptmann et al, 1974), C2 (Klemperer et al, 1966), C3 (Ballow et al, 1975), C5 (Rosenfeld et al, 1976), C6 (Leddy et al, 1974), C7 (Boyer et al, 1975;Gelgge et aI,, 1977;Nemerow et aL, 1978), and C8 (Petersen et al, 1976), and two inactivators of the complement system, C1 inhibitor (Donaldson and Evans, 1963), and C3b inactivator (Abramson et al, 1971;Thompson and Lachmann, 1977). Few cases of ninth component (C9), the terminal component of the complement sequence, have been reported.…”

“…Thus, levels of C9 protein in serum of normal homozygote (C9, C9), heterozygote (C9, C9), and deficient homozygote (C9, C~) approximately reflected the dosage effect of the wild type and mutant gene. Some of the known defects of complement components in man, including C2 (Klemperer et al, 1966;Fu et al, 1974;Day et al, 1975), C3 (Alper and Rosen, 1979), C5 (Rosenfeld et aI., 1976;Snyderman et al, 1979), C6 (Leddy et al, 1974;Lim et al, 1976;Glass et al, 1978), C7 (Boyer et al, 1975;Gelftge et al, 1977;Nemerow et al, 1978), and C8 (Petersen et al, 1976) appear to be inherited in the same mode as is C9. One of the well documented exceptions to this mode of inheritance is the deficiency of C1 inhibitor (Donaldson and Evans, 1963), causative pathogenesis of hereditary angioedema.…”

Functionally active complement proteins C6 and C7 detected in C6- and C7-deficient individuals

“…In addition, meningococcaemia has been reported in a case of acquired terminal complement deficiency due to hepatic failure (Ellison et al, 1986). Individual examples of C6 and C7 deficiencies have also been found in patients with systemic (Tedesco et al, 1981;Zeitz et al, 1981) or discoid lupus erythematosus (Trapp et al, 1987), Sjogrens syndrome (Trapp et al, 1987), recurrent bronchopulmonary infections (Glass et al, 1978), rheumatic illness (Boyer et al, 1975), arthritis with antinuclear antibodies (Reinitz et al, 1986), haematuria (Sakano et al, 1988) and other diseases. Population screening has revealed the existence of healthy C6-and C7-deficient indiCorrespondence: Reinhard Wurzner, MD, MRC Molecular Immunopathology Unit, University of Cambridge, Hills Road, GB-Cambridge CB2 2QH, UK.…”