Potential utility of autoantibodies as blood-based biomarkers for early detection and diagnosis of Parkinson's disease

被引:30
作者
DeMarshall, Cassandra A. [1 ,2 ,3 ]
Han, Min [1 ,2 ,3 ]
Nagele, Eric P. [1 ,5 ]
Sarkar, Abhirup [1 ,2 ,3 ]
Acharya, Nimish K. [1 ,3 ]
Godsey, George [2 ,3 ]
Goldwaser, Eric L. [1 ,2 ,3 ]
Kosciuk, Mary [1 ,3 ]
Thayasivam, Umashanger [4 ]
Belinka, Benjamin [5 ]
Nagele, Robert G. [1 ,3 ,5 ]
机构
[1] Rowan Univ, Sch Osteopath Med, New Jersey Inst Successful Aging, Biomarker Discovery Ctr, Stratford, NJ 08084 USA
[2] Rowan Univ, Grad Sch Biomed Sci, Stratford, NJ 08084 USA
[3] Rowan Univ, Sch Osteopath Med, Dept Geriatr & Gerontol, Stratford, NJ 08084 USA
[4] Rowan Univ, Dept Math, Glassboro, NJ USA
[5] Durin Technol Inc, New Brunswick, NJ USA
基金
美国国家卫生研究院;
关键词
Parkinson's disease; Autoantibodies; Diagnosis; Protein microarrays; Biomarkers; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; CEREBROSPINAL-FLUID;
D O I
10.1016/j.imlet.2015.09.010
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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. (C) 2015 The Authors. Published by Elsevier B.V.
引用
收藏
页码:80 / 88
页数:9
相关论文
共 36 条
  • [1] Low clinical diagnostic accuracy of early vs advanced Parkinson disease Clinicopathologic study
    Adler, Charles H.
    Beach, Thomas G.
    Hentz, Joseph G.
    Shill, Holly A.
    Caviness, John N.
    Driver-Dunckley, Erika
    Sabbagh, Marwan N.
    Sue, Lucia I.
    Jacobson, Sandra A.
    Belden, Christine M.
    Dugger, Brittany N.
    [J]. NEUROLOGY, 2014, 83 (05) : 406 - 412
  • [2] Submandibular gland needle biopsy for the diagnosis of Parkinson disease
    Adler, Charles H.
    Dugger, Brittany N.
    Hinni, Michael L.
    Lott, David G.
    Driver-Dunckley, Erika
    Hidalgo, Jose
    Henry-Watson, Jonette
    Serrano, Geidy
    Sue, Lucia I.
    Nagel, Thomas
    Duffy, Amy
    Shill, Holly A.
    Akiyama, Haruhiko
    Walker, Douglas G.
    Beach, Thomas G.
    [J]. NEUROLOGY, 2014, 82 (10) : 858 - 864
  • [3] CSF α-synuclein does not differentiate between parkinsonian disorders
    Aerts, M. B.
    Esselink, R. A. J.
    Abdo, W. F.
    Bloem, B. R.
    Verbeek, M. M.
    [J]. NEUROBIOLOGY OF AGING, 2012, 33 (02) : 430.e1 - 430.e3
  • [4] AVRAMEAS S, 1991, IMMUNOL TODAY, V12, P154
  • [5] Interleukin 20 protein locates to distinct mononuclear cells in psoriatic skin
    Bech, Rikke
    Otkjaer, Kristian
    Birkelund, Svend
    Vorup-Jensen, Thomas
    Agger, Ralf
    Johansen, Claus
    Iversen, Lars
    Kragballe, Knud
    Romer, John
    [J]. EXPERIMENTAL DERMATOLOGY, 2014, 23 (05) : 349 - 352
  • [6] Motor and non-motor correlates of olfactory dysfunction in Parkinson's disease
    Berendse, Henk W.
    Roos, Dareia S.
    Raijmakers, Pieter
    Doty, Richard L.
    [J]. JOURNAL OF THE NEUROLOGICAL SCIENCES, 2011, 310 (1-2) : 21 - 24
  • [7] Random forests
    Breiman, L
    [J]. MACHINE LEARNING, 2001, 45 (01) : 5 - 32
  • [8] Blood-Based Protein Biomarkers for Diagnosis of Alzheimer Disease
    Doecke, James D.
    Laws, Simon M.
    Faux, Noel G.
    Wilson, William
    Burnham, Samantha C.
    Lam, Chiou-Peng
    Mondal, Alinda
    Bedo, Justin
    Bush, Ashley I.
    Brown, Belinda
    De Ruyck, Karl
    Ellis, Kathryn A.
    Fowler, Christopher
    Gupta, Veer B.
    Head, Richard
    Macaulay, S. Lance
    Pertile, Kelly
    Rowe, Christopher C.
    Rembach, Alan
    Rodrigues, Mark
    Rumble, Rebecca
    Szoeke, Cassandra
    Taddei, Kevin
    Taddei, Tania
    Trounson, Brett
    Ames, David
    Masters, Colin L.
    Martins, Ralph N.
    [J]. ARCHIVES OF NEUROLOGY, 2012, 69 (10) : 1318 - 1325
  • [9] When Does Parkinson's Disease Begin?
    Gaig, Carles
    Tolosa, Eduardo
    [J]. MOVEMENT DISORDERS, 2009, 24 (14) : S656 - S664
  • [10] Biomarker candidates of neurodegeneration in Parkinson's disease for the evaluation of disease-modifying therapeutics
    Gerlach, Manfred
    Maetzler, Walter
    Broich, Karl
    Hampel, Harald
    Rems, Lucas
    Reum, Torsten
    Riederer, Peter
    Stoeffler, Albrecht
    Streffer, Johannes
    Berg, Daniela
    [J]. JOURNAL OF NEURAL TRANSMISSION, 2012, 119 (01) : 39 - 52