Fig. 4
From: Type I interferon-mediated autoinflammation due to DNase II deficiency
Interferon signaling in patients with mutations in DNASE2, STING and TREX1, and in controls. a Heat map derived from RNA-Seq expression data of the top 50 genes ranked by p value (DNASE2-mutated patients vs. controls) with the most significant at the top. 41 of these 50 genes are considered as interferon-stimulated. Lanes 1-14 show individual samples: Lane 1 DNASE2 F1:V-1; lane 2 DNASE2 F1:V-3; lane 3 DNASE2 F1:V-3; lane 4 TREX1 P1; lane 5 TREX1 P2; lane 6 STING P1; lane 7 STING P2, lane 8 STING P3; lanes 9–14 individual healthy controls (HC). b Levels of interferon alpha (IFNα) protein assayed by digital ELISA in plasma or serum from healthy controls (HC: n = 20), patients with mutations in STING (n = 28 samples from 8 patients), patients with mutations in TREX1 (n = 4 samples from 4 patients), F1:V-1 (6 samples taken over 3 years), F1:V-3 (7 samples taken over 3 years) and F2:II-4 (2 samples taken over 3 years). Red lines indicate median values. c Analysis of IFNα production by cultured T cells, B cells, natural killer (NK) cells or monocytes from controls (HC; n = 4), and patients with mutations in DNASE2 (F1:V-1 1 sample; F1:V-3 2 samples), STING (n = 3) or TREX1 (n = 1). d Increased phosphorylation of STAT1 and STAT3 observed in unstimulated CD3 positive T cells and CD14 positive monocytes from total blood of F1:V-3 compared to a healthy control (HC). e Increased phosphorylation of STAT1 and STAT3 observed in cultured lymphocytic-enriched fractions from F1:V-1 compared to a healthy control (HC), treated or not with the JAK1/2 inhibitor ruxolitinib. Similar results were obtained with cells from F1:V-3. f Increased expression of selected interferon-stimulated genes in cell fractions enriched for lymphocytes from F1:V-1, F1:V-3 and F2:II-4 with or without ruxolitinib
