Autoimmune and Inflammatory Mechanisms in Cervical Dystonia

There are many causes for cervical dystonia (CD), although most cases are idiopathic and a cause cannot be identified. The observation that 10-15% of cases have an affected family member has pointed to genetic causes, but known genes account for only a small fraction of all cases. The current manuscript describes a series of studies focusing on potential autoimmune or inflammatory mechanisms in CD. First, a case-control survey for 32 autoimmune diseases in 271 subjects with CD confirmed prior anecdotal observations that CD is associated with thyroid disease, which often results from autoimmune mechanisms. Second, unbiased proteomic methods involving a total of 20 subjects with CD, with or without associated thyroid disease, pointed towards a series of overlapping mechanisms relating to the immune system. Third, a multiplex immunoassay focusing on 37 markers associated with neuroinflammation applied to a total of 20 subjects with CD with or without thyroid disease and 20 controls pointed to abnormalities in several specific measures of the immune system. Finally, a broad screening test for neuronal antibodies in a total of 58 subjects with CD did not disclose any specific antibodies. Altogether, the association of CD with thyroid disease and blood-based immune measures point to abnormalities in cell-mediated immunity that may play a pathogenic role for a subgroup of subjects with CD. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported in part by grants to the Dystonia Coalition (U54 NS065701, U54 TR001456, and U54NS116025), a consortium of the Rare Diseases Clinical Research Network (RDCRN) that is supported by the Office of Rare Diseases Research (ORDR) at the National Center for Advancing Clinical and Translational Studies (NCATS) in collaboration with the National Institute for Neurological Diseases and Stroke (NINDS). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Emory IRB provided approval. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data utilized for these manuscripts is available upon request.