Rheumatoid Arthritis (RA)

Panel A Study design. VAV1-degrader and Adalimumab were administered 40 days post first immunization.

Panel B The administration of VAV1-degraders and Adalimumab significantly decreased arthritis score compared to CIA modeling group.

Panel C Adalimumab treatment significantly ameliorated serum TNF-α and IFN-γ levels compared to CIA modeling group.

Panel D Adalimumab treatment significantly alleviated cell numbers of myeloid cells and nuetrophils in spleen FACS compared to CIA modeling group.

Panel E Representative images of H&E stained slides of hind paw. Note: Cartilage erosion (blue arrows), bone erosion (green arrows), cartilage loss (brown arrows), pannus (purple arrows), fibrous connective tissue proliferation (yellow arrows), mononuclear cells (red arrows). Top row: Scale bar = 200 μm; bottom row: Scale bar = 50 μm.

Panel F Representative images of TRAP staining slides of hind paw. Note: Osteoclasts (green arrows). Top row: Scale bar = 200 μm; bottom row: Scale bar = 50 μm.

Panel G Representative images of Safranin-O/fast green staining green staining slides of hind paw. Note: Cartilage layer (red arrows), focal cartilage defects (green arrows), rough surface with an incomplete tidemark (yellow arrows). Top row: Scale bar = 200 μm; bottom row: Scale bar = 50 μm.

Panel H The administration of VAV1-degrader and Adalimumab significantly mitigated histology score of hind paw.

Data are expressed as mean ± standard error (Mean ± SEM), n=6-8. Statistics performed using One-way ANOVA. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.

Panel A Study design. Dexamethasone was administered 4 days post antibody injection.

Panel B Dexamethasone treatment significantly decreased left limb swelling and right limb swelling compared to CAIA modeling group.

Panel C Dexamethasone treatment significantly ameliorated left limb thickness and right limb thickness compared to CAIA modeling group.

Panel D Dexamethasone treatment significantly mitigated arthritis score compared to CAIA modeling group.

Panel E Representative images of H&E, TRAP, and Safranin-O/fast green staining slides of hind paw.

Panel F Dexamethasone treatment significantly inhibited histology score of hind paw in the aspects of bone erosion, proteoglycan loss, and cartilage erosions compared to CAIA modeling group.

Data are expressed as mean ± standard error (Mean ± SEM), n=6-8. Statistics performed using One-way ANOVA. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.

Panel A Study design. huHSC-NCG-M mice capable of reconstituting human T cells, B cells, and myeloid cells were applied to the study. Adalimumab was administered on the day of modeling.

Panel B Adalimumab treatment significantly ameliorated body weight loss compared to AIA modeling group.

Panel C Adalimumab treatment significantly decreased left hind paw thickness and right hind paw thickness compared to AIA modeling group.

Panel D Adalimumab treatment significantly mitigated arthritis score compared to AIA modeling group.

Data are expressed as mean ± standard error (Mean ± SEM), n=5-8. Statistics performed using One-way ANOVA. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.

Panel A Study design. Adalimumab was administered on the day of modeling.

Panel B Adalimumab treatment significantly ameliorated left hind paw thickness and right hind paw thickness compared to AIA modeling group.

Panel C Adalimumab treatment significantly mitigated arthritis score compared to AIA modeling group.

Panel D Adalimumab treatment significantly inhibited mRNA expression of TNF-α, IL-1β, and IL-6 in hind paw footpad tissues compared to AIA modeling group.

Panel E Adalimumab treatment showed no significant inhibition on the histology score of hind paw compared to the AIA modeling group.

Data are expressed as mean ± standard error (Mean ± SEM), n=7-8. Statistics performed using One-way ANOVA. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.

Panel A  Study design. Data are expressed as mean ± standard error (Mean ± SEM), n=4-6. Statistics performed using One-way ANOVA. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.

Panel B DTHA modeling in B6, B6-hPD1, and B6-hPD1/PDL1 mice significantly increased hind paw thickness difference, hind paw swelling volume difference, and arthritis score compared to B6 healthy control.

Panel C DTHA modeling in B6, B6-hPD1, and B6-hPD1/PDL1 mice significantly elevated serum TNF-α and IL-6 levels 9 days after first immunization compared to B6 healthy control.

Panel D Representative images of H&E, TRAP, and Safranin-O/fast green staining slides from hind paw tissues.

Panel E Compared to B6 healthy control, DTHA modeling in B6, B6-hPD1, and B6-hPD1/PDL1 mice significantly increased histology score of hind paw tissues in the aspects of promoting proteoglycan loss, cartilage erosion, bone erosion, and joint inflammation.