The neural-immune crosstalk in Tourette syndrome: From immunobiology to epistemology

The role of immunity in the pathogenesis of Tourette syndrome (TS) has been a growing topic of interest over the past few decades. From a developmental perspective, it is established that the immune system, and particularly microglia play a role in refining of neural networks; therefore, alterations in the immune balance may impact neurodevelopment. In clinic-based and registry-based studies, associations between TS and allergies, autoimmunity, and atopy have been reported. Several immunity-related genes have been identified in association with TS through genome-wide association studies (GWAS) as well as transcriptomics analyses, both on post-mortem brain specimens and peripheral blood of TS subjects. Furthermore, various environmental exposures that may skew the immune response have been linked with TS, including infections and psychosocial stress. The immunophenotypes of people with TS have been compared to matched controls through numerous studies and methods, identifying altered immune cell populations, cytokine profiles, and evidence of CNS inflammation. In general, the reported immunophenotypes tend to be of a pro-inflammatory nature. Many of these results are discrepant and require replication in the future. A small number of studies have explored immune-based therapies in TS with varying results, although methodological issues limit interpretation and clinical application at this stage. We summarize the current state of knowledge regarding immunity and infections in TS pathogenesis and potential for immune-based therapies, together with theoretical aspects covering the epistemological status of hot topics in this field.