title: Verification of a Parkinson's disease protein signature in T-lymphocytes by multiple reaction monitoring.
abstract: Diagnosis of Parkinson's disease, the second most common neurodegenerative disease, is based on the appearance of motor symptoms. A panel of protein biomarkers in the T-lymphocyte proteome was previously proposed as a Parkinson's disease signature. Here, we designed an LC-MS based method to quantitatively evaluate this protein signature by multiple reaction monitoring (MRM) in T-lymphocytes and peripheral blood mononuclear cells from a new cohort of nine patients with Parkinson's disease and nine unaffected subjects. Patients were classified using the discriminant function obtained from two-dimensional electrophoresis and protein amounts measured by MRM, thus assigning seven controls out of nine as true negatives and nine patients out of nine as true positives. A good discriminant power was obtained by selecting a subset of peptides from the protein signature, with an area under the receiver operating characteristic curve of 0.877. A similar result is achieved by evaluating all peptides of a selected panel of proteins (gelsolin, moesin, septin-6, twinfilin-2, lymphocyte-specific protein 1, vimentin, transaldolase), with an area under the curve of 0.840. Conversely, the signature was not able to classify the enrolled subjects when evaluated in whole mononuclear cells. Overall, this report shows the portability of the proposed method to a large-scale clinical validation study.
authors.affiliation: Division of Biomedical Sciences, Department of Theoretical and Applied Sciences, University of Insubria . Via Luciano Manara 7, Busto Arsizio I-21052, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Alberio
authors.forename: Kelly
authors.initials: K
authors.lastname: McMahon
authors.forename: Manuela
authors.initials: M
authors.lastname: Cuccurullo
authors.forename: Lee A
authors.initials: LA
authors.lastname: Gethings
authors.forename: Craig
authors.initials: C
authors.lastname: Lawless
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zibetti
authors.forename: Leonardo
authors.initials: L
authors.lastname: Lopiano
authors.forename: Johannes P C
authors.initials: JP
authors.lastname: Vissers
authors.forename: Mauro
authors.initials: M
authors.lastname: Fasano
mesh_terms: D000595:Amino Acid Sequence; D019540:Area Under Curve; D015415:Biomarkers / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D016002:Discriminant Analysis; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D008969:Molecular Sequence Data; D010300:Parkinson Disease / Q000175:diagnosis* / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D003598:Cytoskeletal Proteins; D010455:Peptides