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Published on: September 20, 2021
Integrative profiling of untreated primary membranous nephropathy at the single-cell transcriptome level
Qiuhua Gu1, Yuchen Wen2,3, Xi Cheng1
1Department of Nephrology, Tianjin Medical University General Hospital, Tianjin, China.
Background:
Primary membranous nephropathy (PMN) is an autoimmune kidney disease. Despite the identification of certain autoantigens, the etiology and pathophysiology of PMN are still largely unknown.
Methods:
Five patients with biopsy-proven PMN were enrolled in this study. Their blood, kidney and urine samples were collected respectively to profile cellular, molecular and immunological alterations by using single-cell RNA sequencing (scRNA-seq). Experimental verifications were also implemented in kidney tissue.
Results:
In the peripheral blood mononuclear cell (PBMC) samples, portions of B cells and plasma cells were increased in PMN patients. Cell-cell communication analysis suggests that APRIL (a proliferation-inducing ligand from B cells) might be a potential molecule that regulates the activity of plasma cells. In the kidney samples, scRNA-seq analysis showed that the infiltration of T cells, as well as the myeloid cells, appears abundant compared with healthy controls, suggesting that immune cells are actively recruited to kidney. Furthermore, we observed an enhanced interaction between inflammatory cells and podocytes, which might contribute to kidney injury. Accordingly, scRNA-seq analysis of urinary samples is partially reminiscent of the kidney cell landscape, especially T cells and myeloid cells, suggesting monitoring urinary samples is a promising method to monitor PMN development. Additionally, integrative analysis across the blood, kidney and urine identified LTB, HERP1, ANXA1, IL1RN and ICAM1 as common regulators of PMN. Finally, immune repertoire in PBMC also showed an elevated diversity of clonal type, implying the existence of autoreactive T-cell receptor/B-cell receptor.
Conclusion:
Our study comprehensively profiled the transcriptomic landscapes of blood, kidney and urine in patients with PMN using scRNA-seq. We depicted the alterations including cell compositions and cell-cell communication in PMN. These results offer important clues with regard to the diagnosis and pathogenesis of PMN and potential intervention of PMN progression.
Insights
Primary membranous nephropathy (PMN) involves immune cell changes in blood, kidney, and urine. This study used scRNA-seq to reveal cellular alterations and identify key regulators for PMN diagnosis and treatment.
Area of Science:
- Immunology
- Nephrology
- Genomics
Background:
- Primary membranous nephropathy (PMN) is an autoimmune kidney disease with unknown etiology and pathophysiology.
- Certain autoantigens have been identified, but a comprehensive understanding is lacking.
Purpose of the Study:
- To profile cellular, molecular, and immunological alterations in PMN patients using single-cell RNA sequencing (scRNA-seq).
- To identify potential diagnostic and therapeutic targets for PMN.
Main Methods:
- Collected blood, kidney, and urine samples from five biopsy-proven PMN patients.
- Utilized scRNA-seq to analyze transcriptomic landscapes and cell-cell communication.
- Performed experimental verifications in kidney tissue.
Main Results:
- Increased B cells and plasma cells observed in peripheral blood mononuclear cells (PBMC), with APRIL identified as a potential regulator.
- Abundant infiltration of T cells and myeloid cells in kidney tissue, indicating active immune cell recruitment.
- Urinary cell landscape analysis showed promise for monitoring PMN development.
- Identified LTB, HERP1, ANXA1, IL1RN, and ICAM1 as common PMN regulators.
- Elevated diversity of clonal types in PBMC suggests autoreactive T-cell receptor/B-cell receptor.
Conclusions:
- scRNA-seq comprehensively profiled PMN, revealing alterations in cell composition and communication.
- Findings provide insights into PMN pathogenesis, diagnosis, and potential interventions.
