Single-cell RNA-sequencing reveals distinct immune cell subsets and signaling pathways in IgA nephropathy

Abstract

Background IgA nephropathy (IgAN) is the most common primary glomerulonephritis globally. Increasing evidence suggests the importance of host immunity in the development of IgAN, but its dynamics during the early stage of IgAN are still largely unclear. Results Here we successfully resolved the early transcriptomic changes in immune cells of IgAN by conducting single-cell RNA-sequencing (scRNA-seq) with peripheral blood mononuclear cells. The differentially expressed genes (DEGs) between control and IgAN were predominantly enriched in NK cell-mediated cytotoxicity and cell killing pathways. Interestingly, we discovered that the number and cytotoxicity of NK cells are significantly reduced in IgAN patients, where both the number and marker genes of NK cells were negatively associated with the clinical parameters, including the levels of urine protein creatinine ratio (UPCR), serum galactose-deficient IgA1 and IgA. A distinctive B cell subset, which had suppressed NFκB signaling was predominantly in IgAN and positively associated with disease progression. Moreover, the DEGs of B cells were enriched in different viral infection pathways. Classical monocytes also significantly changed in IgAN and a monocyte subset expressing interferon-induced genes was positively associated with the clinical severity of IgAN. Finally, we identified vast dynamics in intercellular communications in IgAN. Conclusions We dissected the immune landscape of IgAN at the single-cell resolution, which provides new insights in developing novel biomarkers and immunotherapy against glomerulonephritis.

Plasma exosomal IRAK1 can be a potential biomarker for predicting the treatment response to renin-angiotensin system inhibitors in patients with IgA nephropathy

“…DEGs screening was performed by the "limma" package from R (18). Genes satisfying the conditions of adjusted P value <0.10 and | log2(fold change) |> 0.58 were defined as DEGs between the sensitive group and resistance group (19,20). All DEGs were drawn as heatmaps with the R package "pheatmap".…”

Comparison of the Single-Cell Immune Landscape of Testudines from Different Habitats

“…In contrast to the findings of previous studies, CD14 and CD16 were not expressed in the peripheral blood monocytes of the testudines, while six marker genes, LGALS1, LY86, PLBD1, MYOF, BPI, and CSF1R, were highly expressed and enriched in response to positive regulation of stimulus and stress, leukocyte chemotaxis, and migration (Supplementary Figure S2A). Previous studies have shown that LGALS1, LY86, PLBD1, BPI, and CSF1R were expressed in monocytes [38][39][40][41][42]. MYOF was observed to be expressed in monocytes for the first time; it was mainly involved in biological processes of response to temperature stimulus and syncytium formation (Supplementary Figure S2B).…”

Fucose as a potential therapeutic molecule against the immune-mediated inflammation in IgA nepharopathy: An unrevealed link

“…The brown module had the highest correlation with IgAN clusters, and 15 hub genes were screened from it according to appropriate thresholds, which were considered to be markers of severe inflammation in IgAN glomeruli. KEGG enrichment analysis indicated that these 15 hub genes were involved in various immune processes such as NK cell–mediated cytotoxicity and cell killing pathways, which are related to the progression and prognosis of IgAN ( 40 ). In addition, hub genes were involved in the complement and coagulation cascades, which play a crucial role in IgAN progression and renal function decline ( 41 ).…”