A B S T R A C T Metabolic properties of the four subclasses of human IgG were investigated by performing 47 turnover studies in individuals with normal IgG serum concentrations, as well as in patients with an increased level of one of the subclasses. Studies in 12 subjects with normal IgG serum concentration showed that the average biologic half-life of Gi, G2, and Ga was 21 days, while that of Gs was only 7.1 days. Fractional catabolic rates of Ga, G2, and G4 were 6.9 to 8% of the intravascular pool per day. Gs, however, had a higher fractional catabolic rate, amounting to 16.8% of the intravascular pool per day. Distribution of the subclasses was such that the intravascular compartment contained 51-54% of the total body pools of Ga, G2, and G4, but 64% of the total body pool of Ga.The short survival and high fractional catabolic rate of Ga is an inherent property of these molecules, and is -not due to denaturation during isolation and radiolabeling. This was demonstrated by studies of a patient -with a serum G3-myeloma protein. The survival of her -own protein, separately labeled either in vivo with guanidoarginine-"4C or in vitro with 'I, was determined in the patient. Survivals of the in vivo and in vitro labeled proteins were identical.Ga and Ga serum concentrations and synthetic rates -were determined. The mean serum concentration of GL was 6.8 mg/ml and that of Gs was 0.7 mg/ml, while their synthetic rates were 25.4 and 3.4 mg/kg per day respectively. The low serum concentration of IgG3 thus -results from a combination of high catabolic and low synthetic rates.Studies in 10 patients with multiple myeloma showed -that an elevated serum concentration of any IgG subclass was associated with shortened biologic half-life and increased fractional catabolic rate of all subclasses. The implications of this concentration-catabolism rela-
The sequences of the 35 and 36 amino-terminal amino acids of two purified amyloid fibril proteins have been determined. Results indicate that these two proteins are derived from homogeneous immunoglobulin light chains of variable region subgroup V(kappaI). The relation between amyloidosis and immunoglobulins is thus more firmly established.
"Amyloid" fibrils have been created from some human Bence Jones proteins by proteolytic digestion under physiologic conditions. These fibrils with an antiparallel, beta-pleated sheet conformation consist of only a portion of the variable region of the immunoglobulin light polypeptide chain and share the physical properties of amyloid fibrils. The relation between amyloidosis and immunoglobulins is thus more firmly established and a pathogenetic mechanism for amyloid fibril formation is suggested.
The metabolism of albumin and IgG was investigated in two siblings, products of a first-cousin marriage, a female aged 34 yr and a male aged 17, who had a marked reduction in their respective serum concentrations of IgG (1.3 and 3.1 mg/ml) and albumin (19 and 21 mg/ml). The metabolism of radioiodinated IgG and albumin was studied in the two patients. The total circulating and body pools of IgG were < 28% of normal. The IgG synthetic rates were within the normal range. However, the IgG survival was short, with their respective fractional catabolic rates increased fivefold to 31% and 36% of the intravenous pool per day (normaL 6.7±2%/d). Furthermore, the patients had reduced total body pools, normal synthetic rates, and increased fractional catabolic rates for albumin. There was no proteinuria or abnormality of renal or liver function. In addition, the patients did not have circulating antibodies directed toward IgG, IgA, or albumin. Furthermore, both patients had normal fecal 51Cr-labeled albumin tests, thus excluding excessive gastrointestinal protein loss. We propose that these siblings have a previously unrecognized familial disorder characterized by reduced serum concentrations of IgG and albumin caused by a defect in endogenous catabolism, leading to a short survival ofthese proteins that is associated in this family with chemical diabetes and a skeletal deformity. (J. Clin.
Three subclasses of human gamma(2)-globulin (IgG) molecules were detected in normal human serum with antiserums prepared in monkeys. These subclasses, designated gamma(2a)-, gamma(2b)-, and gamma(2c)-globulins, have antibody activity. The distinguishing antigenic characteristics of each subclass were associated with the heavy polypeptide chains and the F (fast) fragments resulting from treatment of gamma(2)-globulins with papain.
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