Patients with CGD display a dysregulated hyperinflammatory status. (A) Uniform manifold approximation and projection (UMAP) visualization of scRNA-seq profiles of 50 959 white blood cells from 5 patients with CGD and 5 age- and sex-matched healthy control (HC) colored according to cell type identity. (B) UMAP visualization of cells colored by condition, HC (green) and CGD (purple), downsampled to 3000 cells per donor. (C) Numbers of DEGs identified as upregulated (red) or downregulated (blue) in neutrophils, CD14⁺ monocytes, and CD16⁺ monocytes. (D) Gene functional enrichment analysis based on DEGs upregulated or downregulated in neutrophils, CD14⁺ monocytes, CD16⁺ monocytes, and neutrophils using HALLMARK gene sets. Illustrated are all significant terms (adjusted P < .05). Dots are colored by directionality of differential expression (red, upregulated DEGs; blue, downregulated DEGs). Dot size depicts the number of DEGs in the respective HALLMARK term. (E) Volcano plot of differential abundance of plasma circulatory proteins in patients with CGD (n = 5) as compared with HC (n = 14). Results are displayed as log₂fold change (FC) of CGD compared with HC, plotted against minus log₁₀ of the adjusted P values. Proteins significantly differentially expressed (with adjusted P < .05 after correction for multiple testing) are displayed in red. (F) IL-8 production after 4-hour stimulation in neutrophils from CGD (n = 5) and HC (n = 12) with either medium (RPMI), heat-killed C albicans UC820 (1 × 10⁶ yeast per mL), or PMA (50 ng/mL). (G) IL-6 and IL-1β production after 24-hour stimulation in CGD monocytes (n = 5) and HC (n = 13, except for the stimulations RPMI 10% human pooled serum (HPS) and A fumigatus where n = 4) with either medium (RPMI, with or without 10% HPS) or LPS (10 ng/mL), Pam₃Cys (10 μg/mL), heat-killed C albicans UC820 (1 × 10⁶ yeast per mL), live A fumigatus (1 × 10⁶ conidia per mL) in the presence of 10% HPS, S aureus ATCC 29213 (1 × 10⁶ colony-forming units per mL), or palmitic acid (C16:0; 50  μM) in combination with monosodium urate crystals (300  μg/mL). (H-I) Volcano plot of differential protein abundance from 24 hour-unstimulated (H) and A fumigatus–stimulated (I) Peripheral blood mononuclear cells in culture supernatants of CGD and HC monocytes. Results are displayed as log₂-FC of CGD (n = 5) compared with HC (n = 14), plotted against minus log₁₀ of the P values. Proteins with significantly differential abundance (with adjusted P < .05 after correction for multiple testing) are displayed in red. (J) IL-6 production after 24-hour LPS (10 ng/mL)-restimulation at day 6 after BCG (5 μg/mL)-training protocol of monocytes from HC (n = 5) and patients with CGD (n = 6). (F-G, J) Data are presented as the means ± standard error of the mean (SEM). In the bar plots, different colors indicate different mutations in patients with CGD as indicated by the panel legends. For the enzyme-linked immunosorbent assay results, statistical analysis was performed using the Mann-Whitney U test between patients and HC; a 2-sided P value < .05 was considered statistically significant. C16, palmitate; MSU, monosodium urate; mDc, myeloid dendritic cells; NK, natural killer; pDC, plasmacytoid dendritic cells; Plt. act., platelet-activated; Pam₃Cys, (S)-(2,3-bis(palmitoyloxy)-(2RS)-propyl)-N-palmitoyl-(R)-Cys-(S)-Ser(S)-Lys₄-OH, trihydrochloride; TNF, tumor necrosis factor.