TY - JOUR
T1 - Potential utility of autoantibodies as blood-based biomarkers for early detection and diagnosis of Parkinson's disease
AU - The Parkinson's Study Group Investigators
AU - DeMarshall, Cassandra A.
AU - Han, Min
AU - Nagele, Eric P.
AU - Sarkar, Abhirup
AU - Acharya, Nimish K.
AU - Godsey, George
AU - Goldwaser, Eric L.
AU - Kosciuk, Mary
AU - Thayasivam, Umashanger
AU - Belinka, Benjamin
AU - Nagele, Robert G.
N1 - Funding Information:
The authors would like to thank Gerald Carey and Thuy Vo for their help with Figure 2. This study was supported by the Michael J. Fox Foundation and the Osteopathic Heritage Foundation. The DATATOP study was supported primarily by Public Health Service grant NS24778 from the National Institutes of Health.
Funding Information:
The authors have the following competing interests: R. Nagele has received research funding from the Michael J. Fox Foundation, the Osteopathic Heritage Foundation, GlaxoSmithKline, the Foundation Venture Capital Group, and the Boye Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. R. Nagele is also Co-Founder of Durin Technologies, Inc., serves as its Chief Scientific Officer and has received consulting fees. He may accrue revenue in the future based on patents submitted by Rowan University wherein he is a co-inventor. B. Belinka is also Co-Founder of Durin Technologies, Inc., serves as its Chief Executive Officer and has received consulting fees. He may accrue revenue in the future based on patents submitted by Rowan University. A patent has been submitted for the PD autoantibody biomarker panel. There are no marketed products to declare.
Publisher Copyright:
© 2015 The Authors.
PY - 2015/11/1
Y1 - 2015/11/1
N2 - Introduction: There is a great need to identify readily accessible, blood-based biomarkers for Parkinson's disease (PD) that are useful for accurate early detection and diagnosis. This advancement would allow early patient treatment and enrollment into clinical trials, both of which would greatly facilitate the development of new therapies for PD. Methods: Sera from a total of 398 subjects, including 103 early-stage PD subjects derived from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) study, were screened with human protein microarrays containing 9,486 potential antigen targets to identify autoantibodies potentially useful as biomarkers for PD. A panel of selected autoantibodies with a higher prevalence in early-stage PD was identified and tested using Random Forest for its ability to distinguish early-stage PD subjects from controls and from individuals with other neurodegenerative and non-neurodegenerative diseases. Results: Results demonstrate that a panel of selected, blood-borne autoantibody biomarkers can distinguish early-stage PD subjects (90% confidence in diagnosis) from age- and sex-matched controls with an overall accuracy of 87.9%, a sensitivity of 94.1% and specificity of 85.5%. These biomarkers were also capable of differentiating patients with early-stage PD from those with more advanced (mild-moderate) PD with an overall accuracy of 97.5%, and could distinguish subjects with early-stage PD from those with other neurological (e.g., Alzheimer's disease and multiple sclerosis) and non-neurological (e.g., breast cancer) diseases. Conclusion: These results demonstrate, for the first time, that a panel of selected autoantibodies may prove to be useful as effective blood-based biomarkers for the diagnosis of early-stage PD.
AB - Introduction: There is a great need to identify readily accessible, blood-based biomarkers for Parkinson's disease (PD) that are useful for accurate early detection and diagnosis. This advancement would allow early patient treatment and enrollment into clinical trials, both of which would greatly facilitate the development of new therapies for PD. Methods: Sera from a total of 398 subjects, including 103 early-stage PD subjects derived from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) study, were screened with human protein microarrays containing 9,486 potential antigen targets to identify autoantibodies potentially useful as biomarkers for PD. A panel of selected autoantibodies with a higher prevalence in early-stage PD was identified and tested using Random Forest for its ability to distinguish early-stage PD subjects from controls and from individuals with other neurodegenerative and non-neurodegenerative diseases. Results: Results demonstrate that a panel of selected, blood-borne autoantibody biomarkers can distinguish early-stage PD subjects (90% confidence in diagnosis) from age- and sex-matched controls with an overall accuracy of 87.9%, a sensitivity of 94.1% and specificity of 85.5%. These biomarkers were also capable of differentiating patients with early-stage PD from those with more advanced (mild-moderate) PD with an overall accuracy of 97.5%, and could distinguish subjects with early-stage PD from those with other neurological (e.g., Alzheimer's disease and multiple sclerosis) and non-neurological (e.g., breast cancer) diseases. Conclusion: These results demonstrate, for the first time, that a panel of selected autoantibodies may prove to be useful as effective blood-based biomarkers for the diagnosis of early-stage PD.
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U2 - 10.1016/j.imlet.2015.09.010
DO - 10.1016/j.imlet.2015.09.010
M3 - Article
C2 - 26386375
AN - SCOPUS:84942521999
VL - 168
SP - 80
EP - 88
JO - Immunology Letters
JF - Immunology Letters
SN - 0165-2478
IS - 1
ER -