Blaese R M, Strober W, Levy A L, Waldmann T A
J Clin Invest. 1971 Nov;50(11):2331-8. doi: 10.1172/JCI106731.
The Wiskott-Aldrich syndrome is an immune deficiency disorder with an impairment of both humoral and cellular immune responses. Metabolic turnover studies of IgG, IgA, IgM, and albumin were conducted in seven patients with the Wiskott-Aldrich syndrome using purified radioiodinated proteins. The survival of each of the proteins studied was significantly shortened with a half-time of 7.5 days for IgG (normal 22.9 +/-4 SD), 3.0 days for IgA (normal 5.8 +/-1), 5.0 days for IgM (normal 10.1 +/-2.1), and 8.6 days for albumin (normal 17, range 13-20); the fractional catabolic rates were correspondingly elevated and the distribution of protein among the body compartments was normal. For three of the four proteins. IgG, IgA, and albumin, the steady-state synthetic rates were generally elevated leading to normal or even elevated serum proteins levels. Thus, in the case of IgA, the synthetic rate averaged five times normal while the fractional degradative rate was twice normal. The resulting serum concentration was, therefore, significantly elevated, IgM represented an exception to this pattern in that the increased rate of degradation was not counterbalanced by an increased synthetic rate and, therefore, the serum levels were low. Albumin clearance studies using albumin-(51)Cr showed gastrointestinal protein loss in these patients to be slightly greater than normal, but this could account for only a small fraction of the hypercatabolism observed. There was no proteinuria or abnormalities of thyroid, adrenal, renal, or liver function. Thus, none of the previously recognized causes of increased serum protein catabolism were present. Patients with the Wiskott-Aldrich syndrome, therefore, have a unique disorder of serum protein metabolism characterized by endogenous hypercatabolism of at least four major serum proteins. This phenomenon may be related to reticuloendothelial hyperfunction since the Wiskott-Aldrich syndrome is associated with reticuloendothelial hyperplasia and accelerated clearance of colloidal materials from the plasma.
威斯科特-奥尔德里奇综合征是一种免疫缺陷疾病，其体液免疫和细胞免疫反应均受损。使用纯化的放射性碘化蛋白对7例威斯科特-奥尔德里奇综合征患者进行了IgG、IgA、IgM和白蛋白的代谢转换研究。所研究的每种蛋白质的存活时间均显著缩短，IgG的半衰期为7.5天（正常为22.9±4标准差），IgA为3.0天（正常为5.8±1），IgM为5.0天（正常为10.1±2.1），白蛋白为8.6天（正常为17，范围为13 - 20）；蛋白质分解代谢率相应升高，且蛋白质在身体各部分的分布正常。对于四种蛋白质中的三种，即IgG、IgA和白蛋白，稳态合成率通常升高，导致血清蛋白水平正常甚至升高。因此，就IgA而言，合成率平均为正常的五倍，而分解代谢率为正常的两倍。因此，其血清浓度显著升高。IgM是这种模式的一个例外，因为降解率的增加没有被合成率的增加所抵消，所以血清水平较低。使用白蛋白 -（51）铬进行的白蛋白清除研究表明，这些患者胃肠道的蛋白质丢失略高于正常，但这仅占所观察到的高分解代谢的一小部分。没有蛋白尿，也没有甲状腺、肾上腺、肾脏或肝功能异常。因此，不存在先前公认的血清蛋白分解代谢增加的原因。所以，威斯科特-奥尔德里奇综合征患者有一种独特的血清蛋白代谢紊乱，其特征是至少四种主要血清蛋白的内源性高分解代谢。这种现象可能与网状内皮系统功能亢进有关，因为威斯科特-奥尔德里奇综合征与网状内皮增生以及血浆中胶体物质清除加速有关。
