Impairment of Trk-neurotrophin receptor by the serum of a patient with subacute sensory neuropathy

Background: Paraneoplastic peripheral neuropathy is sometimes associated with unidentified neuronal autoantibodies. Objective: To examine the effects of serum from a patient with subacute sensory axonopathy on the function of the Trk high-affinity nerve growth factor receptor. Patient: An 86-year-old man with sensory neuropathy exhibiting an autoantibody to Trk. Methods: Immunoblot analyses of the brain homogenates and immunoprecipitation were performed with human sera. We further examined the effect of sera on nerve growth factor-induced neurite outgrowth and Trk autophosphorylation. Results: The patient showed sensory nerve axonopathy without well-known paraneoplastic autoantibodies. His serum inhibited nerve growth factor-induced neurite outgrowth and Trk autophosphorylation in PCtrk cells. Moreover, the patient's serum, but not control serum, immunoprecipitated Trk and recognized Trk in brain homogenates as well as in Trk immunoprecipitates. Conclusion: These data strongly suggest that an anti-Trk autoantibody might cause subacute sensory neuropathy.