Soybel D, Jaspan J, Polonsky K, Goldberg I, Rayfield E, Tager H
J Clin Endocrinol Metab. 1983 Mar;56(3):612-8. doi: 10.1210/jcem-56-3-612.
To evaluate the relationship between glucagon antibody antigenic determinants and selective reactivity with plasma void volume (Vo) and lower molecular weight immunoreactive glucagon (IRG) components, we studied plasma IRG levels and molecular profiles in normal subjects and patients with disturbances in plasma glucagon levels using three glucagon antibodies, 30K and P7 raised against the whole peptide and antibody X4 raised against the C-terminal tryptic fragment of glucagon. In normal subjects and pancreatectomized patients, plasma IRG levels were 2- to 3-fold higher with the C-terminus-directed antibody X4 than with either 30K or P7, but in glucagonoma and uremic patients, this discrepancy was smaller. Gel filtration analysis revealed that these antibodies reacted identically with 3500 mol wt IRG and 9000 mol wt IRG in normal, glucagonoma, pancreatectomized, and uremic plasma. Relative immunoreactivity of Vo IRG was approximately 5:2:1 with antibodies X4, 30K, and P7, respectively. In two subjects with unexplained hyperglucagonemia, recovery of IRG was entirely in the Vo, with antiserum X4 reacting one third as well as 30K and P7 not reacting at all. Furthermore, this material did not dilute out in parallel to glucagon standard. These data indicate differential immunoreactivity of the high molecular weight circulating IRG component, with a series of three glucagon antibodies reacting similarly with all other plasma IRG fractions, and suggest that Vo IRG material in plasma is predominantly the result of an immunologically cross-reacting peptide sequence in a plasma protein. The selective immunoreactivity of this component with different antibodies has important implications for the glucagon RIA and may have some bearing on other immunoassays as well.
为了评估胰高血糖素抗体抗原决定簇与血浆空体积（Vo）和低分子量免疫反应性胰高血糖素（IRG）成分的选择性反应性之间的关系，我们使用三种胰高血糖素抗体（针对全肽产生的30K和P7以及针对胰高血糖素C末端胰蛋白酶片段产生的抗体X4）研究了正常受试者和血浆胰高血糖素水平紊乱患者的血浆IRG水平和分子谱。在正常受试者和胰腺切除患者中，C末端导向的抗体X4检测到的血浆IRG水平比30K或P7高2至3倍，但在胰高血糖素瘤和尿毒症患者中，这种差异较小。凝胶过滤分析显示，这些抗体在正常、胰高血糖素瘤、胰腺切除和尿毒症血浆中与3500 mol wt IRG和9000 mol wt IRG的反应相同。Vo IRG与抗体X4、30K和P7的相对免疫反应性分别约为5:2:1。在两名原因不明的高胰高血糖素血症患者中，IRG完全在Vo中恢复，抗血清X4的反应性为30K的三分之一，而P7根本不反应。此外，可以看出该物质不像胰高血糖素标准品那样呈平行稀释。这些数据表明高分子量循环IRG成分具有不同的免疫反应性，这三种胰高血糖素抗体与所有其他血浆IRG组分的反应相似，提示血浆中的Vo IRG物质主要是血浆蛋白中免疫交叉反应肽序列的结果。该成分与不同抗体的选择性免疫反应性对胰高血糖素放射免疫分析具有重要意义，可能对其他免疫分析也有一定影响。
