In:
Clinical Kidney Journal, Oxford University Press (OUP)
Abstract:
Primary membranous nephropathy (PMN) is an autoimmune kidney disease. Despite the identification of certain autoantigens, etiology and pathophysiology of the 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 PBMC samples, portions of B cells and plasma cells were increased in PMN patients. Cell-cell communication analysis suggests that APRIL 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 to healthy controls, suggesting 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 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 TCR/BCR. 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.
Type of Medium:
Online Resource
ISSN:
2048-8505
,
2048-8513
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2024
detail.hit.zdb_id:
2656786-6
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