Fig. 6. Unmodified, citrullination-dependent epitopes stimulate ACPA⁺SE⁺ RA patient CD4⁺ T cells more robustly than native antigen–derived epitopes.

a PBMCs from ACPA⁺SE⁺ RA patients (n = 10), ACPA^–SE⁺RA patients (n = 8), and SE⁺ healthy controls (n = 10) were stimulated with created peptides (1–4), no change peptides (5–7), and destroyed peptides (8–10) derived from NAPA (Fig. 5a). Percentage of CD154⁺CD4⁺ T-cell response to each peptide is shown. b Percentage of potential T-cell responses (where the number of potential T-cell responses were defined as total patients per group multiplied by the total peptides per group) is shown. Two-sided χ² tests were used to compare the frequency of T-cell responses between patient groups. Only significant P values (≤0.05) are shown. c Distribution of ACPA⁺SE⁺ RA patient CD4⁺ T-helper subsets (denoted in legend) in either the total CD4⁺ or the CD4⁺CD154⁺ T-cell population in response to stimulation with created, no change, or destroyed peptides. d ACPA⁺SE⁺ RA patient (n = 18) PBMC cytokine secretion in response to 48-h stimulation with the created peptide pool, normalized to unstimulated samples. The dotted line at a fold change of 1 represents the normalized unstimulated values. Data are presented as median and IQR.