1. %) samples. In these patients an immunoblot analysis was used to rule out antibodies directed against well-defined intracellular target antigens. A specific anti-neuronal binding pattern could not be seen in any of the tissue sections. == Conclusions == The results negate that CASPR2 antibodies play a role in the pathogenesis of Tourette syndrome and do not support the assumption that anti-neuronal antibodies are involved. Keywords:Tourette syndrome, Antineuronal antibodies, CASPR2, NMDAR, Tic == Findings == == Introduction == Gilles de la Tourette syndrome is a chronic neuro-psychiatric disorder with an estimated prevalence rate of about 0.61 % [1]. It is thought that pathophysiologically both genetic vulnerability and environmental factors including immunological changes – SYM2206 are involved. Supporting an immunopathogenic influence, elevated concentrations of Tumor necrosis factor alpha (TNF-) and Interleukin 12 (IL-12) have been detected in patients with GTS [2]. In addition, positive oligoclonal bands in the cerebrospinal fluid have been found in 38 % of GTS patients [3]. This strongly suggests a pathological intrathecal immunoglobulin synthesis in GTS, because positive OCBs are SYM2206 found in only 3 % of the general population. However, the role of autoantibodies in GTS remains unclear, since contradictory results have been found [4]. In the last decade, several antibodies targeting neuronal surface proteins (especially ion channels) have been identified to be causative in different neurological disorders including idiopathic limbic encephalitis (LE) and Morvans syndrome [5]. For example in LE AMPA SYM2206 receptor antibodies (AMPA 1 and AMPA 2), which are directed against the GluA1 and GluA2 subunits of AMPA receptors, can be found. In Morvans syndrome, characterized by peripheral nerve hyperexcitability, an association with the contactin-associated protein 2 (CASPR2) has been demonstrated [6]. Accordingly, clinical improvement following immunotherapy has been reported [7]. In addition, CASPR2 is a known genetic risk factor of autism and has been suggested to play a role in several other neurodevelopmental disorders including ADHD and OCD [8]. CASPR2, expressed in juxtaparanodal regions of myelinated axons prominently in the brain, is linked to voltage gated potassium channels (VGKC) [9]. It is encoded by the contactin-associated protein 2 gene (CNTNAP2). Most interestingly, a disruption of the CNTNAP2 gene by chromosome insertion has been found in a GTS family in both the affected father and two affected children. The authors speculated that the disruption leads to a disturbed distribution of K+channels causing unwanted movements like tics [10]. So far, only one other family – without GTS – has been described with a disrupted CNTNAP2 gene [11]. This observation led to the conclusion that not the disruption of the CNTNAP2 gene, but a dysfunction of the ion channel by CASPR2 antibodies might be causative in GTS. The aim of this study was PHF9 to investigate for the first time CASPR2 antibodies in sera of a large group of adult patients with GTS. == Methods == In this study, we included 51 consecutive adult patients with GTS according to DSM-IV-TR confirmed by one of the authors (KMV). All patients were recruited from the Tourettes outpatient clinic at the Hannover Medical School. Blood samples were collected after approval by the ethics committee of the Hannover Medical School. SYM2206 Patients with autoimmune diseases of the CNS were not eligible to participate. All patients gave their written informed consent before entering the study. From each patient 7.5 mL blood were drawn, centrifuged at 3500 rpm for 15 min, and serum fresh frozen at 80 C. Within one year serum was tested for antibodies using plasmid transfected HEK293 cells (Autoimmune-Encephalitis-Mosaik1 SYM2206 CA 14392, Euroimmun, Lbeck, Germany). The transfected cells ectopically.
