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.

This study was supported by funding from National Medical Research Council (NMRC) CSA award (Y.X.C.), CSIRG (Y.X.C.), STaR award (E.K.T.) and the NMRC Parkinson’s disease Large Collaborative Grant. These authors contributed equally: Yin Xia Chao, Bernett TK Lee. National Neuroscience Institute (NNI), Singapore, Singapore Yin Xia Chao, Suh Yee Goh, Muhammad Yaaseen Gulam, Jolene SY Tan, Ee-Wei Lim, Kumar M.

Tan & Eng-King Tan DUKE-NUS Medical School, Singapore, Singapore Yin Xia Chao, Jolene SY Tan, Ee-Wei Lim, Kumar M. Tan & Eng-King Tan Centre for Biomedical Informatics, Lee Kong Chian School of Medicine, NTU, Singapore, Singapore Singapore Immunology Network (SIgN), A-STAR, Singapore, Singapore Bernett TK Lee, Anis Larbi & Olaf Rötzschke Infectious Disease Labs (ID Labs), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore Khoo Teck Puat Hospital, Singapore, Singapore Department of Psychological Medicine, Yong Loo Lin School of Medicine, NUS, Singapore, Singapore Sengenics Corporation, Singapore, Singapore Correspondence to Yin Xia Chao, Bernett TK Lee or Eng-King Tan. J.M.B. declares the existence of a financial competing interest.

During the course of this study, J.M.B. was under the employment Sengenics. However, he was only involved in the intellectual contribution of this project. The other authors declare no competing financial or non-financial interests.

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