Fig. 3: Impact of sex and age on disease activity and the proteome.

Violin chart of the DAS28-CRP scores grouped by sex in ACPA-positive (a) or ACPA-negative (b) RA patients (two-sided Student’s t test). Scatter plot with fitted regression lines illustrating Spearman’s correlation (two-sided p value) between age and DAS28-CRP grouped by sex in ACPA-positive (c) or ACPA-negative RA (d). Gray band represents 95% confidence interval estimated using standard error of the mean (SEM). e DE-SWAN analysis of proteins across age in ACPA-positive females, with a peak at age 45 indicated by the red line. f Violin plot illustrating age-specific differences in DAS28-CRP and 4 clinical indicators (VAS, SJC, TJC and CRP) in ACPA-positive females aged above and below 45 years (two-sided Student’s t test). g–i Multiple linear regression analysis (adjusted for age and sex, two-sided p value < 0.05) between DAS28-CRP indicators and proteins in ACPA-positive RA patients (n = 175). Bar plot showing the number of proteins significantly correlated with DAS28-CRP indicators (g), bubble plot displaying the regression analysis between proteins and DAS28-CRP (h), and dot plot visualizing the regression analysis between proteins and VAS, TJC, SJC and CRP (i). j Venn diagram showing the overlap of proteins that exhibit significant changes between ACPA-positive females below and above 45 years or are significantly correlated with DAS28-CRP (left). Boxplots (right upper) displaying the normalized intensity of overlapped proteins across ACPA-positive females below and above 45 years (two-sided Student’s t test). Scatter plots (right below) showing regression analysis between proteins and DAS28-CRP (adjusted for age and sex, two-sided p value). Gray band represents 95% confidence interval estimated using SEM. ACPA⁺ indicates ACPA-positive, and ACPA⁻ indicates ACPA-negative. Significance is indicated as follows: *p < 0.05 and **p < 0.01. For box plots shown in (a, b, f, j), the center line represents the median; the bounds of the box indicate the 25th and 75th percentiles; and the whiskers extend to the minimum and maximum values. Source data are provided as a Source Data file.