Fig. 1.

tACPA prevents disease progression in CAIA mice. a A schematic overview of the CAIA mouse model of IA. Mice were injected with the anti-CII antibody mixture, followed by LPS at day 3, to induce acute arthritis. Antibody (Ab) treatment started directly after LPS injection by administration of hz-tACPA (6.25, 12.5, or 25 mg/kg), cIgG (25 mg/kg) or PBS (No Ab). Fifty mg/kg antibody was used in the experiment in which h-tACPA LALANA was compared with h-tACPA and cIgG. The mice were terminated on days 10–13. b The mean arthritis score (MAS) of CAIA mice was evaluated for 13 days (n = 5 mice per group; cIgG was used to calculate significant differences). c Prior to anti-CII antibody mixture and LPS injection, the mice were immunized with different posttranslationally modified H2A and H4 peptides (Supplementary Table 2), including unmodified H2A and H4 (H2A + H4), citrullinated H2A (citH2A), citrullinated H4 (citH4), phosphorylated H2A and H4 (phosH2A + phosH4), acetylated H2A and H4 (acH2A + acH4), and symmetric and asymmetric methylated H4 (sdmH4 + admH4). Non-immunized mice (no peptide) were used as controls. Only mice that developed a specific immune response against these peptides were selected for inclusion in the CAIA experiment (Supplementary Table 3). The MAS of immunized CAIA mice was evaluated at day 10 (n = 3–9 mice per group; the mean of the ‘No peptide’ group was set at 100%, and individual percentages were calculated). d The MAS of CAIA mice was evaluated for 12 days (n = 4–5 mice per group; h-tACPA and h-tACPA LALANA were used to calculate significant differences). The results are presented as the means ± SEM. *P < 0.05, **P < 0.01, using two-tailed Mann–Whitney statistical test