Molecular characteristics of circulating B cells and kidney cells at the single-cell level in special types of primary membranous nephropathy

作者全名："Feng, Xiaoqian; Chen, Qilin; Zhong, Jinjie; Yu, Sijie; Wang, Yue; Jiang, Yaru; Wan, Junli; Li, Longfei; Jiang, Huimin; Peng, Liping; Wang, Anshuo; Zhang, Gaofu; Wang, Mo; Yang, Haiping; Li, Qiu"

作者地址："[Feng, Xiaoqian; Chen, Qilin; Zhong, Jinjie; Yu, Sijie; Jiang, Yaru; Wan, Junli; Jiang, Huimin; Peng, Liping; Wang, Anshuo; Zhang, Gaofu; Wang, Mo; Yang, Haiping; Li, Qiu] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab ChildInfect & Immun, Minist Educ,Key Lab Child Dev & Disorders,Dept Nep, Chongqing, Peoples R China; [Wang, Yue; Li, Longfei] Nanjing Jiangbei New Area Biopharmaceut Publ Serv, Nanjing, Jiangsu, Peoples R China"

通信作者："Yang, HP; Li, Q (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Chongqing Key Lab ChildInfect & Immun, Minist Educ,Key Lab Child Dev & Disorders,Dept Nep, Chongqing, Peoples R China."

来源：CLINICAL KIDNEY JOURNAL

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001090785400001

JCR分区：Q1

影响因子：3.9

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：B cells; podocytes; primary membranous nephropathy; scBCR-seq; scRNA-seq

摘要："Background Although primary membranous nephropathy (pMN) associated with podocyte autoantibodies (POS) is becoming well-known, the molecular characteristics of the specific type of pMN that is negative for podocyte autoantibodies (NEG) is still unclear.Methods We performed single-cell transcriptome sequencing and single-cell B cell receptor sequencing on circulating CD19+ cells and kidney cells of a NEG paediatric patient with pMN. The single-cell datasets of POS patients and healthy control individuals were included for integrative analysis.Results The gene expression characteristics and clonal expansion of naive and memory B cells in the NEG patient changed significantly. We found that a group of CD38+ naive B cells expanded in the NEG patient, which had the functional characteristics of cell activation. In addition, the conversion between immunoglobulin M (IgM)/IgD and IgG1 in the NEG patient was increased. Parietal epithelial cells (PECs) and podocytes shared similar signature genes (WT1, CLIC5), and new candidate marker genes for PECs, such as NID2, CAV1 and THY1, might contribute to the definition of cell subsets. PECs might have undergone significant changes in the disease, mainly manifested by changes in the expression of CCN2, PLAAT4 and SEPTIN2. The scores of gene sets related to extracellular matrix, cell adhesion and calcium channel in podocytes of the NEG patient was significantly increased. The gene expression of sodium transporter in a group of proximal tubule cells in the disease was significantly increased, especially SLC5A12, which might be related to the oedema of patients.Conclusions Our research demonstrated the cell type-specific molecular features in the circulation and kidney of the NEG pMN patient. Graphical Abstract"

基金机构：We sincerely thank all participants in this study.

基金资助正文：We sincerely thank all participants in this study.