Transcriptional heterogeneity of clonal plasma cells and immune evasion in immunoglobulin light chain amyloidosis
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ORIGINAL ARTICLE
Transcriptional heterogeneity of clonal plasma cells and immune evasion in immunoglobulin light chain amyloidosis Yujia Wang1 · Lushuang Xu1 · Yang Liu2 · Yuzhe Hu1 · Qiang Shi3 · Lixue Jin1 · Lijun Yang1 · Pingzhang Wang1 · Kunshan Zhang4 · Xiaojun Huang2 · Qing Ge1,5,7 · Jin Lu2,6 Received: 2 July 2020 / Revised: 16 September 2020 / Accepted: 28 September 2020 © Japanese Society of Hematology 2020
Abstract 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. Keywords Immunoglobulin light chain amyloidosis · Single-cell RNA sequencing · Plasma cells · Natural killer cells Abbreviations AL Immunoglobulin light chain BM Bone marrow DEG Differentially expressed gene Yujia Wang and Lushuang Xu have contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12185-020-03016-3) contains supplementary material, which is available to authorized users. * Qing Ge [email protected] * Jin Lu [email protected] 1
Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China
2
Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Peking University People’s Hospital and Institute of Hematology, Beijing 100044, China
3
School of Life Sciences, Center for Bioinformatics, Peking University, Beijing 100871, China
ER Endoplasmic reticulum LC Light chain MGUS Monoclonal gammopathy of undetermined significance MM Multiple myeloma NK Natural killer PC Plasma cell scRNA-seq Single-cell RNA sequencing UMAP Uniform manifold approximation and projection 4
Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
5
Department of Integration
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