Myasthenia Gravis (MG)

Panel A Study design. Female B6 mice aged 8-10 weeks were immunized with ACHRα 97-116 peptide on weeks 0, 5, 8, and 11. Mice were sacrificed 12 weeks after the first immunization.

Panel B MG modeling significantly elevated serum IgG and anti‑AChR antibody levels compared with healthy controls throughout the modeling phase.

Panel C MG modeling led to a significant elevation in serum TGF‑β levels relative to healthy controls at the study endpoint.

Panel D MG modeling significantly increased the spleen‑to‑body weight ratio compared with healthy controls at endpoint. MG modeling significantly decreased the thymus‑to‑body weight ratio and gastrocnemius‑to‑body weight ratio compared with healthy controls at endpoint.

Panel E Significant increase in spleen Tfh cells was observed in MG mice relative to healthy mice. An increasing trend in spleen Th1(IFNγ+) and Th17(IL17A+) cells was observed in MG mice relative to healthy mice.

Panel F The representative images of H&E staining slides using gastrocnemius tissues. Notes: Muscle fiber degeneration and necrosis (black arrow) loose connective tissue inflammatory cell infiltration and fibrous tissue hyperplasia around muscle tissue (green arrow) lymphocytes (blue arrow) neutrophils (yellow arrow) fibrous tissue hyperplasia (orange arrow). The first row: bar = 200 μm; Second row: bar = 50 μm.

Panel G Significant increase in gastrocnemius histology score was observed in MG mice relative to healthy mice.

Data is expressed as mean ± standard error (Mean ± SEM). Statistics performed using One-way ANOVA. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

Title: Efficacy study of Fenebrutinib in the AchR97-116 induced MG model using female B6 mice.

Panel A Study design. Female B6 mice aged 8-10 weeks were immunized with ACHRα 97-116 peptide on weeks 0, 5, 8, and 11. Fenebrutinib administration was initiated on week 5. Mice were sacrificed 12 weeks after the first immunization.

Panel B Fenebrutinib administration showed no significant difference in body weight compared to MG model group.

Panel C Fenebritinib administration significantly inhibited mouse IgG levels compared to the MG model group.

Panel D Representative FACS plots and quantification of splenic T‑cell subsets. A downward trend in Th1 (IFN‑γ⁺) and Th17 (IL‑17A⁺) cell percentages was observed in Fenebrutinib‑treated mice compared with the MG model group.

Data is expressed as mean ± standard error (Mean ± SEM). Statistics performed using One-way ANOVA. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

Panel A Study design. Female NCG mice were reconsitituted with healthy human PBLs or MG patient-derived PBLs on Day 0. Mice were sacrificed 7 weeks (Day 42) after PBL reconstitution.

Panel B No significant differences were observed in body weight or its change between healthy PBL‑NCG and MG PBL‑NCG mice.

Panel C A downward trend in grip strength was observed in MG PBL‑NCG mice relative to healthy PBL‑NCG mice.

Panel D MG PBL reconstitution significantly increased human AChR antibody levels compared to healthy PBL‑NCG mice.

Panel E Representative images of H&E stained slides of tibialis anterior tissues. Notes: muscle fiber degeneration and necrosis, atrophy (black arrow); lymphocytes (blue arrow); fibrous tissue hyperplasia (orange arrow). First row: Bar=100 um; Second row: Bar=20 um.

Panel F Increasing trend in the tibialis anterior inflammation score was observed in MG PBL‑NCG mice relative to healthy PBL‑NCG mice.

Data is expressed as mean ± standard error (Mean ± SEM), n=3. Statistics performed using One-way ANOVA. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.