Fig. 7
tACPA prevents NET-mediated tissue damage and disease progression in chronic CIA mice. a A schematic overview of the CIA mouse model of IA. To induce chronic IA, mice were injected twice (days 0 and 21) with CII. Therapeutic treatment started after onset of the disease (between days 21 and 28), when the MAS was ≥0.75, and included four injections (4-day intervals) with tapered dosing regimens of cIgG (50/50/50/50 mg/kg) or hz-tACPA (30/30/30/10, 50/50/50/15 or 50/10/10/10 mg/kg). The mice were terminated 14 days after the start of treatment. b The MAS of CIA mice was evaluated for 14 days (n = 10 mice per group). c Representative immunofluorescence and H&E images of NET release in joints of right hind paws showing citH3 (red), DAPI (blue), MPO (yellow), and Ly6G (green). Scale bars: 100 µm. d Quantification of NETs (colocalization of citH3 and MPO) in the tibiotarsal, proximal intertarsal, distal intertarsal, and tarsometatarsal joints of the right hind paws of mice (n = 10). e Significant correlation of macroscopic score (paw swelling) and NETs per joint. f Bone damage to the right and left hind knees and ankles was analyzed by X-ray at day 14 after the first antibody injection (n = 10). H&E and SO staining of joints from right and left ankles showing g inflammatory cell influx, h bone erosion, i cartilage erosion, j cartilage PG depletion, and k chondrocyte death at day 14 after the first antibody injection (n = 16–20 mouse ankles). The results are presented as the means ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001 using two-way ANOVA with Dunnett’s multiple comparisons test (b; cIgG was used to calculate significant differences), unpaired two-tailed Student’s t test (d), two-tailed Mann–Whitney statistical test (f–k), or Spearman r test (e)
