Comenzo R L, Zhang Y, Martinez C, Osman K, Herrera G A
Division of Hematologic Oncology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021, USA.
Blood. 2001 Aug 1;98(3):714-20. doi: 10.1182/blood.v98.3.714.
Primary systemic amyloidosis (AL) is a protein conformation disorder in which monoclonal immunoglobulin light chains produced by clonal plasma cells are deposited as amyloid in the kidneys, heart, liver, or other organs. Why patients with AL present with amyloid disease that displays such organ tropism is unknown. This study tested the hypothesis that both the light-chain variable region (Ig V(L)) germ line genes used by AL clones and the plasma cell burden influenced AL organ tropism. To assess the renal tropism of some light chains, an in vitro renal mesangial cell model of amyloid formation was used. With reverse transcription-polymerase chain reaction, Ig V(L) genes were sequenced from 60 AL patients whose dominant involved organs were renal (52%), cardiac (25%), hepatic (8%), peripheral nervous system (8%), and soft tissue and other (7%). Patients with clones derived from the 6a V(lambdaVI) germ line gene were more likely to present with dominant renal involvement, whereas those with clones derived from the 1c, 2a2, and 3r V(lambda) genes were more likely to present with dominant cardiac and multisystem disease. Patients with V(kappa) clones were more likely to have dominant hepatic involvement and patients who met the Durie criteria for myeloma (38%, 23 of 60) were more likely to present with dominant cardiac involvement independent of germ line gene use. In the in vitro model, unlike all other AL light chains tested, lambdaVI light chains formed amyloid rapidly both with and without amyloid-enhancing factor. These data support the hypothesis that germ line gene use and plasma cell burden influence the organ tropism of AL. (Blood. 2001;98:714-720)
原发性系统性淀粉样变性（AL）是一种蛋白质构象紊乱疾病，其中克隆性浆细胞产生的单克隆免疫球蛋白轻链以淀粉样蛋白的形式沉积在肾脏、心脏、肝脏或其他器官中。目前尚不清楚为何AL患者会出现具有这种器官嗜性的淀粉样疾病。本研究检验了以下假设：AL克隆所使用的轻链可变区（Ig V(L)）种系基因和浆细胞负荷均影响AL的器官嗜性。为评估某些轻链的肾脏嗜性，采用了淀粉样蛋白形成的体外肾系膜细胞模型。通过逆转录-聚合酶链反应，对60例AL患者的Ig V(L)基因进行了测序，这些患者的主要受累器官为肾脏（52%）、心脏（25%）、肝脏（8%）、周围神经系统（8%）以及软组织和其他部位（7%）。源自6a V(lambdaVI)种系基因的克隆患者更易出现以肾脏为主的受累情况，而源自1c、2a2和3r V(lambda)基因的克隆患者更易出现以心脏为主的疾病和多系统疾病。具有V(kappa)克隆的患者更易出现以肝脏为主的受累情况，符合骨髓瘤Durie标准的患者（60例中的38%，即23例）更易出现以心脏为主的受累情况，且与种系基因的使用无关。在体外模型中，与所有其他测试的AL轻链不同，lambdaVI轻链无论有无淀粉样蛋白增强因子均能迅速形成淀粉样蛋白。这些数据支持了种系基因的使用和浆细胞负荷影响AL器官嗜性这一假设。（《血液》。2001年；98：714 - 720）
