Characterization of ganglionic acetylcholine receptor autoantibodies

Abstract

In myasthenia gravis (MG), autoantibodies bind to the alpha1 subunit and other subunits of the muscle nicotinic acetylcholine receptor (AChR). Autoimmune autonomic ganglionopathy (AAG) is an antibody-mediated neurological disorder caused by antibodies against neuronal AChRs in autonomic ganglia. Subunits of muscle and neuronal AChR are homologous. We examined the specificity of AChR antibodies in patients with MG and AAG. Ganglionic AChR autoantibodies found in AAG patients are specific for AChRs containing the alpha3 subunit. Muscle and ganglionic AChR antibody specificities are distinct. Antibody crossreactivity between AChRs with different alpha subunits is uncommon but can occur.

Figure 1

A) Neuronal AChR antibody levels for AAG patients (filled circles) and experimental rabbits with EAAG (triangles). B) Relative antibody levels were calculated by normalizing each antibody level to the value for ganglionic AChR antibody (in the same patient). The mean relative antibody levels (± S.E.M.) are shown for each of the AChR subtypes. For α3-type AChR, the data are from 23 patients with AAG and 8 seropositive experimental AAG rabbits. In the case of α4β2, α7 and muscle AChR, the number above the data bar indicates the number of seropositive subjects. *p<0.005 compared to IMR-32 assay (paired t-test).

Figure 2

Antibody effects on AChR current. The whole cell AChR currents elicited by a 4 second application of 50 µM DMPP are shown at baseline and 20 minutes after addition of IgG to the bath solution. IgG from an AAG patient with ganglionic AChR antibodies inhibits the current through all AChR containing the α3 subunit (A, B) but not current through α4β2 (C) or muscle AChR (D, TE671 cells). IgG from a healthy control subject had no effect on any AChR currents (E, F).