Identification of novel autoantibodies in Parkinson’s disease using a functional protein array platform

Autoimmunity has been implicated in Parkinson’s disease (PD), but the role of peripheral autoantibodies is unclear. Using a novel autoantibody screening platform (based on 3D protein structures), a 2-stage case-control study was conducted to identify peripheral autoantibodies in PD. 340 subjects, comprising of 140 age-and-gender-matched participants (50 PD patients and 90 healthy controls (HCs)) in the discovery cohort and a validation cohort involving 200 participants (110 PD patients and 90 HCs) were recruited. A two-pronged analysis approach and gender-corrected analysis identified increased levels of twelve autoantibodies in more PD patients’ plasmas than HCs. A transcriptomic meta-analysis, consisting of 62 datasets, confirmed the dysregulation of these targets in the blood and/or brain of PD patients. STRING analysis revealed that these targets mediate translation regulation and endothelial cell activity and vascular development/angiogenesis. These autoantibodies may be useful as potential diagnostic markers and/or targets for further pathophysiologic and therapeutic studies in PD.