Fig. 4.
Antibody-dependent pathogenicity of bivalent MuSK antibodies. (A) Experimental design of passive transfer in NOD/SCID mice. Mice exposed to bivalent 13–3B5 started to (progressively) lose weight (B), grip strength (C), and hanging time on the inverted mesh (D) in the third and second week of the experiment, respectively. Mice exposed to bivalent 11–3F6 did not show progressive loss on these parameters (B–D). (E) Mice exposed to bivalent 13–3B5 showed a significant ∼30% CMAP decrement at the end point, while bivalent 11–3F6 did not induce a decrement. (F) Contraction force of the diaphragm was significantly, but very mildly (∼3% reduction), affected by 125 nM dTC for mice exposed to bivalent 11–3F6. Data represent mean ± SEM 13–3B5: 5 mg/kg (pink): n = 2; 10 mg/kg (purple): n = 4 (except for hanging time on inverted mesh and EMG: n = 3); 11–3F6: 10 mg/kg: n = 5; b12 (black): n = 2, combined with untreated (gray): n = 5 for CMAP or n = 4 for tetanic contraction).