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

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 (), and new candidate marker genes for PECs, such as and , 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 and . 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 , 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.