Neuronal autoantibodies excite guinea pig myenteric neurons

The role of IgG in effecting gastrointestinal (G.I.) dysmotility associated with neurologic autoimmunity (idiopathic or paraneoplastic) remains poorly defined. Serum IgG prepared from patients with anti-neuronal nuclear autoantibody type 1 (ANNA-1 [aka anti-Hu], n=7) or ganglionic nicotinic acetylcholine receptor (α3AChR, n=6) autoantibody were tested on myenteric neurons in longitudinal muscle myenteric plexus (LMMP) preparations from the ileum of 38 guinea pigs. IgG prepared from healthy subjects or neurologic patients (n=7) without G.I. symptoms served as controls. Action potential discharges in all neurons of a ganglion in response to acute application of IgG were monitored by fast imaging using a voltage-sensitive dye. Data were analysed as% neurons per ganglion responding and frequency of action potential discharge. Only 0.7±1.2% of 708 neurons (26 ganglia) responded to 2 of 7 control IgG samples (mean action potential frequency 0.5±0.9Hz). Six of 7 samples containing ANNA-1-IgG evoked a response in 7.4±5.7% of 1266 neurons (45 ganglia) (P<0.05) with a significantly higher action potential discharge (1.8±1.1Hz, P<0.05). We observed no correlation between ANNA-1 titer and the percentage of responding neurons or action potential frequency. Four of 6 samples containing α3AChR-IgG evoked a response in a smaller number of neurons (6.5±9.9% of 612 neurons (32 ganglia)) with an action potential frequency of 1.9±1.5Hz.

In summary our data indicate that IgG in serum of patients with autoimmune G.I. dysmotilities evoke hyperexcitability in enteric neurons. These findings are consistent with IgGs of neuronal specificity playing an effector role in autoimmune G.I. dysmotilities.