Fig. 2: Compositional changes and activation of the inflammatory pathways in immune cells from VEXAS patients. | Nature Communications

Fig. 2: Compositional changes and activation of the inflammatory pathways in immune cells from VEXAS patients.

From: In depth transcriptomic profiling defines a landscape of dysfunctional immune responses in patients with VEXAS syndrome

Fig. 2

a A neighborhood graph of PBMCs using Milo differential abundance testing. Nodes represent neighborhoods from the PBMC population. A color scale indicates log2-fold change (FC) differences between VEXAS patients and healthy donors. Significant changes are colored in blue and red. Nondifferential abundance Nhoods (a false discovery rate [FDR] ≥ 0.10) are indicated in white. b Beeswarm and box plots showing the distribution of log2FC differences between VEXAS (n = 9) and healthy donors (n = 5) in neighborhoods in different cell type clusters. Colors are represented similarly to (a). A box plot shows median and interquartile ranges (IQR); lower and upper hinges correspond to the first and third quartiles, respectively. An upper whisker extends from the hinge to the largest value no further than 1.5*IQR from the hinge. A lower whisker extends from the hinge to the smallest value at most 1.5*IQR from the hinge. c UMAP plots overlaid with projections of the IFN-α, IFN-γ, and TNF response pathway gene module scores. d Gene module scores of IFN-α, IFN-γ, and TNF responses in PBMCs. A heatmap depicting differences between average scores of VEXAS patients and those of healthy donors in each of 10 cell types. Gene module scores of cells of VEXAS patients were compared to those of healthy donors in each cell type using the two-sided Welch’s t-test and shown as *P < 1.0 × 10–10, **P < 1.0 × 10–100. e Predicted ligand-receptor interactions of significantly upregulated genes in VEXAS patients as compared to healthy donors. f A volcano plot displaying normalized protein expression of cytokines in plasma measured by the Olink Target 96 Inflammation panel immunoassay. The plot shows 92 plasma cytokines differentially expressed between VEXAS patients and healthy donors. x and y axes represent a magnitude of a cytokine’s log2FC and a significance scale by the -log10 (p adjusted [padj]), respectively. A black dotted line indicates padj = 0.05. Significantly dysregulated cytokines are highlighted in red. gdT gamma delta T cells, MAIT mucosa-associated invariant T cell. Source data are provided as a Source Data file.

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