Hyperpolarisation-activated cyclic nucleotide channel 4 (HCN4) involvement in Tourette's syndrome autoimmunity

ObjectivesWe previously found that antibodies in Tourette's syndrome (TS) patients' sera reacted with a 120 kDa protein from rat brain tissue. Here, we sought to identify this protein and determine if it was involved in TS pathogenesis.MethodsThe 120 kDa protein was identified using immunoprecipitation, Western blotting, and mass spectrometry. ELISAs were used to quantify anti-120 kDa protein antibodies in serum of interest using samples from 32 TS patients, 47 patients with attention deficit hyperactivity disorder (ADHD) and 14 healthy controls. Involvement of the 120 kDa protein in TS was confirmed using co-localisation assays with GH3 cells. TS sera were micro-infused into SD rats' brain striatum and their stereotypical behaviours were monitored.ResultsThe brain protein was identified as hyperpolarisation-activated cyclic nucleotide channel 4 (HCN4). TS patients' sera contained significantly more anti-HCN4 antibodies than ADHD patient and control sera. After microinfusing TS serum, SD rats exhibited increased stereotyped tic behaviours, which were correlated with the amount of infused anti-HCN4 antibody.ConclusionsAnti-HCN4 antibodies in the brain might contribute to the pathogenesis of tic symptoms in TS patients. However, further studies are needed to investigate the validity of this animal model of TS induced by microinfusing anti-HCN4 antibody.