title: Proteomic identification of aldolase A as an autoantibody target in patients with atypical movement disorders.
abstract: We tried to identify the target/s of autoantibodies to basal ganglia neurons found in a patient with hyperkinetic movement disorders (HMD) characterized by rapid, rhythmic involuntary movements or spasms in both face and neck. Patient and control sera were used in Western blot to probe mouse brain homogenates. Two-dimensional gel electrophoresis (2-DE) SDS-PAGE protein spots recognized by the patient's antibodies were excised and sequenced by mass spectrometry analysis, and the glycolytic enzyme aldolase A was identified as the antigen recognized by the patient's autoantibodies. To assess relevance and specificity of these antibodies to the identified targets as biomarkers of autoimmunity in movement disorders, autoantibody responses to the identified target were then measured by ELISA in various diseases of the central nervous system. Anti-aldolase A autoantibodies were associated mainly with HMD (7/17, 41%) and Parkinson's disease (4/30, 13%) patients, and undetectable in subjects with other inflammatory and non-inflammatory central nervous system diseases. We, thus, identified aldolase A as an autoantigen in a sub-group of patients with HMD, a clinically ill-defined syndrome. Anti-aldolase A antibodies may represent a useful biomarker of autoimmunity in HMD patients.
authors.affiliation: Division of Neuroscience, Institute for Experimental Neurology, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Privitera
authors.forename: Valeria
authors.initials: V
authors.lastname: Corti
authors.forename: Massimo
authors.initials: M
authors.lastname: Alessio
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Volontè
authors.forename: Antonietta
authors.initials: A
authors.lastname: Volontè
authors.forename: Vito
authors.initials: V
authors.lastname: Lampasona
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.forename: Gianvito
authors.initials: G
authors.lastname: Martino
authors.forename: Diego
authors.initials: D
authors.lastname: Franciotta
authors.forename: Roberto
authors.initials: R
authors.lastname: Furlan
authors.forename: Raffaella
authors.initials: R
authors.lastname: Fazio
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008297:Male; D009069:Movement Disorders / Q000145:classification; D040901:Proteomics; D012189:Retrospective Studies; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D001323:Autoantibodies; D005634:Fructose-Bisphosphate Aldolase