Extended Data Fig. 7: Autoantibodies in DS plasma.
From: Autoimmunity in Down’s syndrome via cytokines, CD4 T cells and CD11c+ B cells
(A) Principal component analysis of HuProt IgA dataset for adult HCs (n = 4), adults with DS (n = 5), and patients, Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) (n = 3) and Autoimmune polyglandular syndrome type 1 (APS-1) (n = 1). (B) Number of IgA autoantigens enriched at least 2-fold in DS, IPEX, and APS-1 compared to HCs. (C) Venn diagram of enriched IgA autoantigens overlapping between disease groups. (D) Heatmap of enriched IgA autoantigens in HCs, DS, IPEX, and APS-1. Colour intensity corresponds to the log2FC expression value relative to the mean of healthy adult controls. (E) Component loadings (PC1 and PC2) from Principal component analysis of HuProt IgG dataset for adults with DS (n = 5) and age-matched HCs (n = 4). (F) ELISA of anti-MSTN and anti-ATP6V1G2 autoantibodies in plasma from HCs (n = 6) and individuals with DS (n = 6). Significance assessed by two-tailed unpaired t tests, * denotes p ≤ 0.05. Whiskers denote min and max values, bounds of box denote Q1–Q3, and centre bar denotes mean. (G) Heatmap of IgG type I IFN autoantigens in HCs, DS, IPEX, and APS-1. Colour intensity corresponds to the log2FC expression value relative to the mean of healthy adult controls. (H) Quantification of antibodies against IFNα2 and IFNω in serum from HCs (n = 32), DS without COVID-19 (n = 10), DS with COVID-19 (n = 6), and APS-1 (n = 1) by Gyros assay. (I) Neutralization of IFNα2 and IFNω activity by serum from HCs (n = 32), DS without COVID-19 (n = 10), DS with COVID-19 (n = 6), and APS-1 (n = 1) by Gyros assay. (H-I) Significance assessed by One-way ANOVA with Tukey’s post-hoc analysis, ns denotes p > 0.05, *p ≤ 0.05; **p ≤ 0.005; ***p ≤ 0.0005; ****p ≤ 0.0001.
