Figure S3.
Transcriptomic and immune profiling indicates a DNA repair signature and interferon-driven immune activation in ATRIP deficient cells. (a) MSigDB hallmark gene sets differentially expressed in PBMCs from F1Pt compared to HCs (n = 3). Normalized enrichment score (NES) values of the gene sets are depicted. (b) Enrichment plots for two MSigDB hallmark gene sets differentially expressed in PBMCs from F1Pt compared to HCs (n = 3). The profile of the running enrichment score (ES) is depicted for both hallmark gene sets. (c) Heatmap displaying the top 20 enriched hallmark gene sets (MSigDB) in T effector cells of F1Pt compared to HCs (n = 3). (d) Heatmap showing the top 20 enriched altered hallmark gene sets (MSigDB) in NK cells of F1Pt compared to HCs (n = 3). (e) Relative expression of six ISGs in whole blood of patient F1Pt compared to HCs (n = 6) (left). For each sample, an ISG score was calculated from the median fold induction of the 6 ISGs (right). The mean ISG score of 6 HCs + 2 SD of the mean was calculated and ISG scores above this threshold (>3.793; indicated by the dotted line) was labeled as positive. (f) Contour plot showing CD4+ T cell maturation in HC and F1Pt. F1Pt (−) represents pre-treatment with anti-CD20 mAb (aCD20), F1Pt (+) represents post-treatment with anti-CD20. (g) Contour plot displaying CD8+ T cell maturation in HC and F1Pt. F1Pt (−) represents pre-treatment with anti-CD20, F1Pt (+) represents post-treatment with anti-CD20. (h) Frequencies of CD4+ T, CD8+ T, NK, and B cells in PBMCs from HCs (n = 18) and F1Pt before and after treatment with anti-CD20. Data represent one experiment, with each data point representing one biological replicate. Mean and SEM are shown. (i) ICOS, OX40, PD1, and CTLA4 expression on CD4+ T cells of HCs (n = 6) and F1Pt before and after treatment with anti-CD20 mAb. Bar plots display median fluorescence (MFI). Mean and SEM are shown. Refer to the image caption for details.

Transcriptomic and immune profiling indicates a DNA repair signature and interferon-driven immune activation in ATRIP deficient cells . (a) MSigDB hallmark gene sets differentially expressed in PBMCs from F1Pt compared to HCs (n = 3). Normalized enrichment score (NES) values of the gene sets are depicted. (b) Enrichment plots for two MSigDB hallmark gene sets differentially expressed in PBMCs from F1Pt compared to HCs (n = 3). The profile of the running enrichment score (ES) is depicted for both hallmark gene sets. (c) Heatmap displaying the top 20 enriched hallmark gene sets (MSigDB) in T effector cells of F1Pt compared to HCs (n = 3). (d) Heatmap showing the top 20 enriched altered hallmark gene sets (MSigDB) in NK cells of F1Pt compared to HCs (n = 3). (e) Relative expression of six ISGs in whole blood of patient F1Pt compared to HCs (n = 6) (left). For each sample, an ISG score was calculated from the median fold induction of the 6 ISGs (right). The mean ISG score of 6 HCs + 2 SD of the mean was calculated and ISG scores above this threshold (>3.793; indicated by the dotted line) was labeled as positive. (f) Contour plot showing CD4+ T cell maturation in HC and F1Pt. F1Pt (−) represents pre-treatment with anti-CD20 mAb (aCD20), F1Pt (+) represents post-treatment with anti-CD20. (g) Contour plot displaying CD8+ T cell maturation in HC and F1Pt. F1Pt (−) represents pre-treatment with anti-CD20, F1Pt (+) represents post-treatment with anti-CD20. (h) Frequencies of CD4+ T, CD8+ T, NK, and B cells in PBMCs from HCs (n = 18) and F1Pt before and after treatment with anti-CD20. Data represent one experiment, with each data point representing one biological replicate. Mean and SEM are shown. (i) ICOS, OX40, PD1, and CTLA4 expression on CD4+ T cells of HCs (n = 6) and F1Pt before and after treatment with anti-CD20 mAb. Bar plots display median fluorescence (MFI). Mean and SEM are shown.

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