Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
Amyloid. 2010 Sep;17(3-4):129-36. doi: 10.3109/13506129.2010.530081.
Light chain amyloidosis (AL amyloidosis) is a haematological disorder in which a clonal population of B cells expands and secretes enormous amounts of the immunoglobulin light chain protein. These light chains misfold and aggregate into amyloid fibrils, leading to organ dysfunction and death. We have studied the in vitro fibril formation kinetics of two patient-derived immunoglobulin light chain variable domain proteins, designated AL-09 and AL-103, in response to changes in solution conditions. Both proteins are members of the κI O18:O8 germline and therefore are highly similar in sequence, but they presented with different clinical phenotypes. We find that AL-09 forms fibrils more readily and more rapidly than AL-103 in vitro, mirroring the clinical phenotypes of the patients and suggesting a possible connection between the fibril kinetics of the disease protein and the disease progression.
轻链淀粉样变性（AL 淀粉样变性）是一种血液系统疾病，其中克隆群体的 B 细胞扩增并分泌大量免疫球蛋白轻链蛋白。这些轻链错误折叠并聚集形成淀粉样纤维，导致器官功能障碍和死亡。我们研究了两种源自患者的免疫球蛋白轻链可变区蛋白，命名为 AL-09 和 AL-103，在溶液条件变化时的体外纤维形成动力学。这两种蛋白均属于 κI O18:O8 胚系，因此在序列上高度相似，但它们表现出不同的临床表型。我们发现，AL-09 在体外比 AL-103更容易和更快地形成纤维，这与患者的临床表现相吻合，表明疾病蛋白的纤维形成动力学与疾病进展之间可能存在联系。
