文章：

免疫球蛋白基因的分子分析揭示了双单克隆伽玛病的克隆相关性

Molecular analysis of immunoglobulin genes reveals frequent clonal relatedness in double monoclonal gammopathies

原文发布日期：2013-04-19

DOI: 10.1038/bcj.2013.12

类型: Original Article

开放获取: 是

英文摘要：

Monoclonal gammopathies (MGs) are hematological diseases characterized by high levels of a monoclonal immunoglobulin (Ig) or M-protein. Within this group are patients with more than one M-protein, referred to as double MGs (DMGs). The M-proteins in DMG patients may have different heavy chain (HC) isotypes that are associated with different light chains (LCs), or different HCs that are LC matched. In this study, we examined the clonal relatedness of the M-proteins in the latter type in a cohort of 14 DMG patients. By using PCR, we identified 7/14 DMG patients that expressed two Ig HC isotypes with identical Ig HC variable (IGHV), diversity (IGHD), joining (IGHJ), and complementarity determining region (HCDR3) sequences. Two additional DMG patients had two Ig transcripts using the same IGHV, IGHD and IGHJ genes but with slight differences in variable region or HCDR3 mutations. LC analysis confirmed that a single LC was expressed in 3/7 DMG patients with identical HC transcripts and in the two DMGs with highly similar transcripts. The PCR findings were confirmed by immunofluorescence for HC and LC expression. Clonally related HC-dissimilar/LC-matched DMGs may occur often and defines a new subtype of MG that may serve as a tool for studies of disease pathogenesis.

摘要翻译： 

单克隆丙种球蛋白病（MGs）是以单克隆免疫球蛋白（Ig）或M蛋白高水平为特征的血液系统疾病。其中存在携带超过一种M蛋白的患者，称为双重MGs（DMGs）。DMG患者的M蛋白可能具有与不同轻链（LCs）相关的重链（HC）同种型，或具有轻链匹配的不同重链。本研究通过PCR技术对14例DMG患者队列中后一类型的M蛋白克隆相关性进行检测，发现7/14的DMG患者表达两种具有相同Ig重链可变区（IGHV）、多样性区（IGHD）、连接区（IGHJ）及互补决定区（HCDR3）序列的Ig重链同种型。另有2例DMG患者虽使用相同的IGHV、IGHD和IGHJ基因，但其可变区或HCDR3区域存在细微突变。轻链分析证实，在3/7具有完全相同重链转录本的DMG患者及2例具有高度相似转录本的DMG患者中均仅表达单一轻链。通过免疫荧光对重链和轻链表达的检测进一步验证了PCR结果。克隆相关的重链相异/轻链匹配型DMGs可能较为常见，这定义了一种新的单克隆丙种球蛋白病亚型，可作为疾病发病机制研究的工具。

原文链接：

Molecular analysis of immunoglobulin genes reveals frequent clonal relatedness in double monoclonal gammopathies