A Systematic Review and Meta-Analysis of Alpha Synuclein Auto-Antibodies in Parkinson's Disease.

Immune dysfunction has been associated with Parkinson's disease (PD) and its progression. Antibodies play an important role in both innate and adaptive responses, acting as powerful effector molecules that can propagate inflammation by activating innate immune cells. Alpha synuclein binding antibodies have been described in PD patients with conflicting associations. In this article, we consider the potential mechanistic basis of alpha synuclein auto-antibody development and function in PD. We present a systematic review and meta-analysis of antibody studies in PD cohorts showing that there is weak evidence for an increase in alpha synuclein auto-antibodies in PD patients particularly in early disease. The confidence with which this conclusion can be drawn is limited by the heterogeneity of the clinical cohorts used, inclusion of unmatched controls, inadequate power and assay related variability. We have therefore made some recommendations for the design of future studies.We received no specific funding for this work. KM Scott is supported by a PhD fellowship from the Wellcome Trust. CH Williams-Gray is supported by a Clinician Scientist fellowship from the Medical Research Council. MR Clatworthy is supported by a Medical Research Council New Investigator Research Grant (MR/N024907/1) and an Arthritis Research UK Cure Challenge Research Grant (21777). This work was also supported by the NIHR Cambridge Biomedical Research Centre