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

Author:

Feng Xiaoqian1,Chen Qilin1,Zhong Jinjie1,Yu Sijie1,Wang Yue2,Jiang Yaru1,Wan Junli1,Li Longfei2,Jiang Huimin1,Peng Liping1,Wang Anshuo1,Zhang Gaofu1,Wang Mo1,Yang Haiping1,Li Qiu1

Affiliation:

1. Department of Nephrology Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics , Chongqing , China

2. Nanjing Jiangbei New Area Biopharmaceutical Public Service Platform , Nanjing, Jiangsu , China

Abstract

ABSTRACT 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 naïve and memory B cells in the NEG patient changed significantly. We found that a group of CD38+ naïve 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.

Funder

National Key Research and Development Program of China

Program for Youth Innovation in Future Medicine

Chongqing Medical University

Natural Science Foundation of Chongqing

Publisher

Oxford University Press (OUP)

Subject

Transplantation,Nephrology

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