Antibodies to L‐periaxin in sera of patients with peripheral neuropathy produce experimental sensory nerve conduction deficits

L‐Periaxin is a PDZ‐domain protein localized to the plasma membrane of myelinating Schwann cells and plays a key role in the stabilization of mature myelin in peripheral nerves. Mutations in L‐periaxin have recently been described in some patients with demyelinating peripheral neuropathy, suggesting that disruption of L‐periaxin function may result in nerve injury. In this study, we report the presence of autoantibodies to L‐periaxin in sera from two of 12 patients with diabetes mellitus (type 2)‐associated neuropathy and three of 17 patients with IgG monoclonal gammopathy of undetermined significance (MGUS) neuropathy, an autoimmune peripheral nerve disorder. By comparison, anti‐L‐periaxin antibodies were not present in sera from nine patients with IgM MGUS neuropathy or in sera from 10 healthy control subjects. The effect of anti‐L‐periaxin serum antibody on peripheral nerve function was tested in vivo by intraneural injection. Sera containing anti‐L‐periaxin antibody, but not sera from age‐matched control subjects, injected into the endoneurium of rat sciatic nerve significantly (p