Fast liver catabolism of C1q in patients with paraproteinaemia and depletion of the classical pathway of complement.
The main clinical features in four patients with IgG1k paraproteinaemia and acquired complement deficiency included xanthomatous skin lesions (in three), panniculitis (in three) and hepatitis (in two). Hypocomplementaemia concerned the early classical pathway components--in particular C1q. Metabolic studies employing 125I-C1q revealed a much faster catabolism of this protein in the four patients than in five normal controls and three patients with cryoglobulinaemia (mean fractional catabolic rates respectively: 23.35%/h; 1.44%/h; 5.84%/h). Various experiments were designed to characterize the mechanism of the hypocomplementaemia: the patients' serum, purified paraprotein, blood cells, bone marrow cells, or xanthomatous skin lesions did not produce significant complement activation or C1q binding. When three of the patients (two with panniculitis and hepatitis) were injected with 123I-C1q, sequential gamma-camera imaging demonstrated rapid accumulation of the radionuclide in the liver, suggesting that complement activation takes place in the liver where it could produce damage.
D000328:Adult; D001853:Bone Marrow / Q000276:immunology; D003166:Complement Activating Enzymes / Q000378:metabolism*; D003167:Complement Activation; D003172:Complement C1 / Q000378:metabolism*; D015922:Complement C1q; D003171:Complement Pathway, Classical; D003165:Complement System Proteins / Q000172:deficiency; D003450:Cryoglobulins / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008099:Liver / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010265:Paraproteinemias / Q000276:immunology*; D012871:Skin Diseases / Q000276:immunology; D014973:Xanthomatosis / Q000276:immunology
D003172:Complement C1; D003450:Cryoglobulins; D007074:Immunoglobulin G; D015922:Complement C1q; D003165:Complement System Proteins; D003166:Complement Activating Enzymes