Diemert M C, Musset L, Gaillard O, Escolano S, Baumelou A, Rousselet F, Galli J
Laboratoire d'Immunochimie, Hôpital Pitié-Salpêtrière, Paris, France.
J Clin Pathol. 1994 Dec;47(12):1090-7. doi: 10.1136/jcp.47.12.1090.
To identify a physico-chemical criterion, or set of criteria, explaining and possibly predicting the nephrotoxic behaviour of Bence-Jones proteins (BJP).
The electrophoretic mobility and isoelectric point (pI) of 92 BJP isolates were determined using various electrophoresis procedures on polyacrylamide gel. The proportions of monomers and dimers were determined using sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS PAGE) in 58 cases. PAGE data for 10 BJP isolates were used to construct Ferguson plots and titration curves.
The distribution of electrophoretic mobility and pI values was bimodal and showed a positive correlation when the pI was above 6. The values of these two parameters in 22 patients with renal impairment were not significantly different from those in the patients without renal impairment, and the statistical analysis showed no predictive value for the onset of renal impairment. However, patients excreting the lambda light chain isotype had a 2.8-fold higher risk of developing renal impairment compared with the other patients. Studies of the charge variation of the protein with pH indicated three types of behaviour, suggesting that the charge of BJP is highly variable at physiological pH.
It is important to study not only the positivity or negativity of the BJP charge at a given pH, but also its intensity. The study of the BJP titration curves in patients with renal impairment suggests that a low charge at physiological urinary pH could predict renal impairment.
确定一种物理化学标准或一组标准，以解释并可能预测本-周蛋白（BJP）的肾毒性行为。
采用多种聚丙烯酰胺凝胶电泳方法，测定了92份BJP分离物的电泳迁移率和等电点（pI）。58例中，采用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）测定单体和二聚体的比例。利用10份BJP分离物的PAGE数据构建弗格森图和滴定曲线。
电泳迁移率和pI值分布呈双峰，当pI高于6时呈正相关。22例肾功能损害患者的这两个参数值与无肾功能损害患者相比无显著差异，统计学分析显示对肾功能损害的发生无预测价值。然而，与其他患者相比，排泄λ轻链同种型的患者发生肾功能损害的风险高2.8倍。蛋白质电荷随pH值变化的研究表明存在三种行为类型，提示BJP在生理pH值下电荷高度可变。
不仅要研究BJP在给定pH值下电荷的正负性，还要研究其强度。对肾功能损害患者BJP滴定曲线的研究表明，生理性尿pH值下电荷低可能预示肾功能损害。
