Morell A, Terry W D, Waldmann T A
J Clin Invest. 1970 Apr;49(4):673-80. doi: 10.1172/JCI106279.
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 G(1), G(2), and G(4) was 21 days, while that of G(3) was only 7.1 days. Fractional catabolic rates of G(1), G(2), and G(4) were 6.9 to 8% of the intravascular pool per day. G(3), 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 G(1), G(2), and G(4), but 64% of the total body pool of G(3).The short survival and high fractional catabolic rate of G(3) 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 G(3)-myeloma protein. The survival of her own protein, separately labeled either in vivo with guanidoarginine-(14)C or in vitro with (125)I, was determined in the patient. Survivals of the in vivo and in vitro labeled proteins were identical.G(1) and G(3) serum concentrations and synthetic rates were determined. The mean serum concentration of G(1) was 6.8 mg/ml and that of G(3) 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 IgG(2) 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 relationship are discussed. The serum concentration of nonmyeloma IgG was usually low in myeloma patients and the synthesis of nonmyeloma IgG was somewhat decreased, suggesting that low serum concentrations of nonmyeloma IgG result from decreased synthesis, as well as from an increased fractional catabolic rate.
通过对血清免疫球蛋白G（IgG）浓度正常的个体以及某一亚类水平升高的患者进行47项周转率研究，对人IgG四个亚类的代谢特性进行了调查。对12名血清IgG浓度正常的受试者的研究表明，IgG1、IgG2和IgG4的平均生物学半衰期为21天，而IgG3仅为7.1天。IgG1、IgG2和IgG4的分解代谢率为每天血管内池的6.9%至8%。然而，IgG3的分解代谢率更高，达到每天血管内池的16.8%。亚类的分布情况是，血管内部分占IgG1、IgG2和IgG4全身池总量的51% - 54%，但占IgG3全身池总量的64%。IgG3的短生存期和高分解代谢率是这些分子的固有特性，并非由于分离和放射性标记过程中的变性所致。这一点通过对一名患有血清IgG3 - 骨髓瘤蛋白的患者的研究得到了证实。分别在体内用胍基精氨酸 - 14C或在体外用125I标记她自身的蛋白，然后在该患者体内测定其生存期。体内和体外标记蛋白的生存期相同。测定了IgG1和IgG3的血清浓度及合成率。IgG1的平均血清浓度为6.8mg/ml，IgG3为0.7mg/ml，而它们的合成率分别为每天25.4mg/kg和3.4mg/kg。因此，IgG2的低血清浓度是高分解代谢率和低合成率共同作用的结果。对10名多发性骨髓瘤患者的研究表明，任何IgG亚类血清浓度升高都与所有亚类的生物学半衰期缩短和分解代谢率增加有关。讨论了这种浓度 - 分解代谢关系的意义。骨髓瘤患者中非骨髓瘤IgG的血清浓度通常较低，且非骨髓瘤IgG的合成有所减少，这表明非骨髓瘤IgG的低血清浓度是合成减少以及分解代谢率增加所致。
