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) are 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 pediatric 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 NEG changed significantly. We found that a group of CD38+ naïve B cells expanded in NEG, which had the functional characteristics of cell activation. In addition, the conversion between IgM/D and IgG1 in NEG 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 NEG were 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 edema of patients.
Conclusions
Our research has demonstrated the cell-type-specific molecular features in the circulation and kidney of the autoantibody-negative pMN patient.