Transcriptional heterogeneity of clonal plasma cells and immune evasion in immunoglobulin light chain amyloidosis
Transcriptional heterogeneity of clonal plasma cells and immune evasion in immunoglobulin light chain amyloidosis
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免疫球蛋白轻链淀粉样变性中克隆浆细胞的转录异质性和免疫逃避
DOI：
10.1007/s12185-020-03016-3
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发表时间：
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影响因子：
2.1
通讯作者：
Jin Lu
中科院分区：
文献类型：
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作者：
Yujia Wang;Lushuang Xu;Yang Liu;Yuzhe Hu;Qiang Shi;Lixue Jin;Lijun Yang;Pingzhang Wang;Kunshan Zhang;Xiaojun Huang;Qing Ge;Jin Lu
免疫球蛋白轻链淀粉样变性（AL淀粉样变性）的特征在于存在产生淀粉样蛋白的免疫球蛋白轻链（LC）的B细胞。AL中异常B细胞的低频率经常被多克隆B细胞背景所掩盖，使得治疗困难。我们分析了GEO数据库中的单细胞RNA测序数据，比较了4名AL淀粉样变性患者、1名治疗后AL受试者和6名健康对照者的浆细胞（PC）。AL衍生的PC在多发性骨髓瘤中已知过表达基因的表达模式及其在LC中V区的使用方面存在高度个体间变异性。我们还发现，在AL淀粉样变性患者中，MHC I类分子的过度表达是克隆PC的共同特征之一。与健康对照组相比，在一小群AL患者中也观察到循环自然杀伤（NK）细胞频率显著降低。这些数据表明，异常PC在AL具有高度多样的转录组，上调的MHC，并通过降低循环NK频率的免疫监视能力减弱。单细胞水平的克隆PC分析可能为AL淀粉样变性的精确分子分型和诊断提供更好的方法。
Immunoglobulin light chain amyloidosis (AL amyloidosis) is characterized by the presence of B cells producing amyloidogenic immunoglobulin light chains (LCs). The low frequency of aberrant B cells in AL is often masked by a polyclonal B cell background, making it difficult for treatment. We analyzed the single-cell RNA sequencing data from GEO database to compare the plasma cell (PCs) in four individuals with AL amyloidosis, one AL subject after treatment, and six healthy controls. High interindividual variability in AL-derived PCs in their expression pattern of known overexpressed genes in multiple myeloma and their usage of V regions in LCs was demonstrated. We also found overexpression of MHC class I molecules as one of the common features of clonal PCs in individuals with AL amyloidosis. Significantly reduced frequencies of circulating natural killer (NK) cells were also observed in a small cohort of AL patients when compared to healthy controls. These data demonstrate that aberrant PCs in AL has a highly diverse transcriptome, an upregulation of MHC, and a dampened capability of immunosurveillance by reduction of circulating NK frequencies. The analysis of clonal PCs at single cell level may provide a better approach for precise molecular profiling and diagnosis of AL amyloidosis.