Autoantibodies Blocking M3 Muscarinic Receptors Cause Postganglionic Cholinergic Dysautonomia

A 10‐year‐old girl presented with ileus, urinary retention, dry mouth, lack of tears, fixed dilated pupils, and diffuse anhidrosis 7 days after a febrile illness. We hypothesized that her syndrome was due to autoimmunity against muscarinic acetylcholine receptors, blocking their activation. Using an indirect enzyme‐linked immunosorbent assay for all 5 muscarinic receptors (M 1 –M 5 ), we identified in the patient's serum antibodies that selectively bound to M 3 receptors. In vitro functional studies confirmed that these autoantibodies selectively blocked M 3 receptor activation. Thus, autoantibodies against M 3 acetylcholine receptors cause acute postganglionic cholinergic dysautonomia. ANN NEUROL 2020;88:1237–1243