Figure 3. IGF1 deficiency is associated with a specific inflammatory profile in DS.
54 inflammatory factors were measured in plasma samples from 309 research participants, 259 of them with T21, versus 50 age- and sex-matched euploid controls (D21) for whom matched measurements of IGF1 signaling factors and neurodegeneration markers were available.
(A) Heatmap displaying correlations in circulating levels of inflammatory markers adjusted by age, sex, and source that are significantly associated, positively or negatively, with IGF1, IGFBP3, IGFALS, IGFBP2, and four neurodegeneration/neuroinflammation biomarkers. Values displayed represent Spearman rho values, and asterisks indicate a significant correlation after multiple hypothesis correction with the method (q < 0.1).
(B) Volcano plots for rho values from Spearman correlations between circulating IGF1 (left) and NfL (right) levels versus circulating levels of inflammatory factors in individuals with T21 after adjustment for age, sex, and source.
(C) Sina plots displaying levels of TNF-α in individuals with and without T21. Boxes indicate median and interquartile range. Differences between groups were determined with a multivariable linear regression with age, sex, and source as covariables, with BH correction of p values.
(D) Scatterplots displaying adjusted values for levels of IGF1 and NfL correlated with levels of TNF-α among individuals with DS. Values shown represent rho values from Spearman correlations and q values calculated with the BH method. Points are colored by density. Lines represent a simple linear regression with 95% confidence interval.
(E and F) Sina plots displaying distributions of the indicated proteins (E) and ages (F) across the five molecular clusters identified among 259 participants with T21. Asterisks indicate q < 0.1 for Mann-Whitney tests of each cluster against cluster 1. Boxes represent medians and interquartile ranges.