Kaplan Batia, Livneh Avi, Gallo Gloria
The Heller Institute of Medical Research, Sheba Medical Centre, Tel-Hashomer, Israel.
Br J Haematol. 2007 Mar;136(5):723-8. doi: 10.1111/j.1365-2141.2006.06488.x.
Immunoglobulin light chain amyloidosis (AL) and non-amyloid light chain deposition disease (NALCDD) are different forms of protein aggregation disorders that may occur in plasma cell dyscrasias with dysproteinemia. In systemic AL, the deposits are fibrillar and patchy in distribution, within and amongst different organs, whereas in NALCDD, the deposits are granular and diffusely distributed in systemic basement membranes, suggesting different mechanisms of aggregation and deposition. Previous evidence, that charge differences between the light chains in AL and NALCDD might account for their different phenotypes, prompted the present study, which compared the isoelectric points (pIs) of AL and NALCDD protein deposits extracted from human tissues. The pI profiles (5.2-8.8) of polypeptides in AL deposits were heterogenous in four cases, with a spread of both anionic and cationic isoforms; in contrast, in three of NALCDD the pI profiles (8.2-8.8) were homogeneous and restricted in the cationic range. These in vivo findings in human disease, together with other reported in vitro and in vivo experimental data, suggest that the fibrillar deposits in AL may form by electrostatic interaction between oppositely charged polypeptides, whereas the granular deposits in NALCDD form by the binding of cationic polypeptides to anionic proteoglycans sites in basement membranes.
免疫球蛋白轻链淀粉样变性（AL）和非淀粉样轻链沉积病（NALCDD）是蛋白聚集性疾病的不同形式，可能发生于伴有异常蛋白血症的浆细胞发育异常中。在系统性AL中，沉积物呈纤维状，在不同器官内及器官间呈斑片状分布，而在NALCDD中，沉积物呈颗粒状，弥漫分布于全身基底膜，提示存在不同的聚集和沉积机制。先前有证据表明，AL和NALCDD中轻链的电荷差异可能解释它们不同的表型，这促使了本研究，该研究比较了从人体组织中提取的AL和NALCDD蛋白沉积物的等电点（pIs）。在4例AL沉积物中，多肽的pI谱（5.2 - 8.8）是异质的，同时存在阴离子和阳离子异构体；相比之下，在3例NALCDD中，pI谱（8.2 - 8.8）是同质的，且局限于阳离子范围。这些关于人类疾病的体内研究结果，连同其他已报道的体外和体内实验数据，表明AL中的纤维状沉积物可能通过带相反电荷的多肽之间的静电相互作用形成，而NALCDD中的颗粒状沉积物则通过阳离子多肽与基底膜中阴离子蛋白聚糖位点的结合形成。
