C3 metabolism in a patient with deficiency of the second component of complement (C2) and discoid lupus erythematosus.
A patient with a hereditary deficiency of the second component of complement and discoid lupus erythematosus with features of systemic lupus erythematosus was studied. The propositus had a 9-year history of rash and arthralgia. Transient renal disease had completely resolved; there was a history of seizures. Examination of his serum disclosed antinuclear antibodies but no total haemolytic complement activity. C2 was absent. Serum concentrations of C1s, C3, C5 and C9 were elevated; other complement components were present in normal concentration, including C3 pro-activator. The patient's C3 pro-activator was electrophoretically converted by inulin and four of five lipopolysaccharides, but was poorly converted by aggregated human IgG. Two separate turnover studies with radiolabelled C3 showed fractional catabolic rates of 3-03 and 2-48% of the remaining plasma pool/hr (range of three normals: 1-62-2-18%/hr); and estimated C3 synthetic rates of 2-74 and 2-31 mg/kg/hr (range of three normals: 0-89-1-40 mg/kg/hr). Serum complement profiles of the patient's family demonstrated that the C2 deficiency was inherited as an autosomal codominant. One sibling, homozygous for C2 deficiency, and three other siblings, both parents and one daughter, all heterozygous for C2 deficiency, are in good health. Immunofluorescent studies of the patient's diseased skin exhibited substantial deposits of IgG, IgM, C1q, and C4 but not of later acting complement components, properdin, or C3 proactivator. These studies do not support the notion that inflammation in C3-deficient individuals with lupus erythematosus is mediated by the alternative complement pathway.
D000328:Adult; D000974:Antibodies, Antinuclear; D003175:Complement C2 / Q000172:deficiency*; D003176:Complement C3 / Q000378:metabolism*; D003169:Complement Inactivator Proteins; D003165:Complement System Proteins / Q000172:deficiency* / Q000378:metabolism*; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D007074:Immunoglobulin G; D007153:Immunologic Deficiency Syndromes / Q000235:genetics; D008179:Lupus Erythematosus, Discoid / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012867:Skin / Q000276:immunology
D000974:Antibodies, Antinuclear; D003175:Complement C2; D003176:Complement C3; D003169:Complement Inactivator Proteins; D007074:Immunoglobulin G; D003165:Complement System Proteins