Potential mechanisms in MuSK-myasthenia gravis

Abstract

Figure 3: A,C: Coomassie gel with non reducing conditions of puri#ed IgG (1), papain digested IgG (2) and puri#ed FAB fragments (3). B,D: RIPA of Plasma, puri#ed IgG and puri#ed FAB fragments as well as healthy control serum. Figure 7: A= IP of MuSK by commercial antibodies against MuSK and patient antibodies, and co-precipitated Lrp4 from cells transfected with MuSK and Lrp4, and transfection control (Lrp4, but no MuSK). B=Healthy control serum. C=IP with patient F or commercial antibody, western blot with antibody against human IgG, FAB speci#c, or against MuSK. D,E= quanti#cation of band size from 5 patients, normalized as % of commercial antibody against MuSK (N=3). 1-way ANOVA + Dunnett’s multiple comparison test. D= MuSK (all ns). E=Lrp4. F= Ratio Lrp4/MuSK. 1-way ANOVA+ Dunnett’s multiple comparison test. Conclusions • FAB-fragments can block agrin induced AChR clustering but do not appear to induce agrinindependent AChR clusters • Therefore, agrin independent AChR clustering by MuSK antibodies appears to be dependent on MuSK dimerization • Binding of MuSK antibodies decreases the interaction between MuSK and Lrp4 Summary of Results • MuSK ab effect on AChR clustering correlate broadly • with MuSK ab titre • FAB fragments as well as IgG reduce agrin induced AChR clustering • FAB fragments, in contrast to IgG, do not induce agrinindependent AChR clustering • Patient antibodies co-precipitate less Lrp4 than commercial antibodies against MuSK • All results are still preliminary, more data required