title: Cytokines in Machado Joseph Disease/Spinocerebellar Ataxia 3.
abstract: The aim of the present study is to describe the serum concentrations of a broad spectrum of cytokines in symptomatic and asymptomatic carriers of Machado Joseph disease (SCA3/MJD) CAG expansions. Molecularly confirmed carriers and controls were studied. Age at onset, disease duration, and clinical scales Scale for the Assessment and Rating of Ataxia (SARA), Neurological Examination Score for Spinocerebellar Ataxias (NESSCA), SCA Functional Index (SCAFI), and Composite Cerebellar Functional Score (CCFS) were obtained from the symptomatic carriers. Serum was obtained from all individuals and a cytokine panel "consisted of" eotaxin, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-α, IFN-γ, interleukin (IL)-1β, IL-1RA, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-15, IL-17, interferon gamma-induced protein (IP)-10, monocyte chemoattractant protein (MCP)-1, monokine induced by gamma interferon (MIG), macrophage inflammatory protein (MIP)-a, MIP-b, regulated on activation, normal T cell expressed and secreted (RANTES) and tumor necrosis factor (TNF)-α was analyzed. In a subgroup of symptomatic carriers, the cytokine panel was repeated after 360 days. Cytokine distribution among groups was studied by discriminant analysis; changes in serum levels after 360 days were studied by generalized estimation equation. Sixty-six symptomatic carriers, 13 asymptomatic carriers, and 43 controls were studied. No differences in cytokine patterns were found between controls and carriers of the CAG expansions or between controls and symptomatic carriers only. In contrast, eotaxin concentrations were significantly higher in asymptomatic than in symptomatic carriers or in controls (p = 0.001, ANCOVA). Eotaxin did not correlate with age, disease duration, CAG expansion, NESSCA score, and SARA score. Among symptomatic carriers, eotaxin dropped after 360 days (p = 0.039, GEE). SCA3/MJD patients presented a benign pattern of serum cytokines. In contrast, levels of eotaxin, a peptide secreted by astrocytes, were elevated in the asymptomatic carriers, suggesting that a specific response of these cells can be related to symptom progression, in SCA3/MJD.
authors.affiliation: Post-Graduate Programme in Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Gerson
authors.initials: G
authors.lastname: da Silva Carvalho
authors.affiliation: Post-Graduate Programme in Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
authors.forename: Jonas Alex Morales
authors.initials: JA
authors.lastname: Saute
authors.affiliation: Post-Graduate Programme in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Clarissa Branco
authors.initials: CB
authors.lastname: Haas
authors.affiliation: Post-Graduate Programme in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Vitor Rocco
authors.initials: VR
authors.lastname: Torrez
authors.affiliation: Post-Graduate Programme in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Andressa Wigner
authors.initials: AW
authors.lastname: Brochier
authors.affiliation: Post-Graduate Programme in Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Gabriele Nunes
authors.initials: GN
authors.lastname: Souza
authors.affiliation: Post-Graduate Programme in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Gabriel Vasata
authors.initials: GV
authors.lastname: Furtado
authors.affiliation: Post-Graduate Programme in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Tailise
authors.initials: T
authors.lastname: Gheno
authors.affiliation: Post-Graduate Programme in Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Russo
authors.affiliation: Post-Graduate Programme in Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Neurology Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
authors.forename: Thais Lampert
authors.initials: TL
authors.lastname: Monte
authors.affiliation: Neurology Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
authors.forename: Artur
authors.initials: A
authors.lastname: Schumacher-Schuh
authors.affiliation: Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
authors.forename: Rui
authors.initials: R
authors.lastname: D'Avila
authors.affiliation: Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
authors.forename: Karina Carvalho
authors.initials: KC
authors.lastname: Donis
authors.affiliation: Post-Graduate Programme in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Raphael Machado
authors.initials: RM
authors.lastname: Castilhos
authors.affiliation: Post-Graduate Programme in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Instituto Nacional de Ciência e Tecnologia em Excitotoxicidade e Neuroproteção (INCTEN), Porto Alegre, Brazil.
authors.forename: Diogo Onofre
authors.initials: DO
authors.lastname: Souza
authors.affiliation: Post-Graduate Programme in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil.|Instituto Nacional de Genética Médica Populacional (INAGEMP), Porto Alegre, Brazil.
authors.forename: Maria Luiza
authors.initials: ML
authors.lastname: Saraiva-Pereira
authors.affiliation: Department of Epidemiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Department of Statistics, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Vanessa Leotti
authors.initials: VL
authors.lastname: Torman
authors.affiliation: Department of Epidemiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Department of Statistics, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Suzi
authors.initials: S
authors.lastname: Camey
authors.affiliation: Post-Graduate Programme in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.|Instituto Nacional de Ciência e Tecnologia em Excitotoxicidade e Neuroproteção (INCTEN), Porto Alegre, Brazil.
authors.forename: Luis Valmor
authors.initials: LV
authors.lastname: Portela
authors.affiliation: Post-Graduate Programme in Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. ljardim@hcpa.edu.br.|Post-Graduate Programme in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. ljardim@hcpa.edu.br.|Department of Internal Medicine, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. ljardim@hcpa.edu.br.|Medical Genetics Service, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil. ljardim@hcpa.edu.br.|Instituto Nacional de Genética Médica Populacional (INAGEMP), Porto Alegre, Brazil. ljardim@hcpa.edu.br.
authors.forename: Laura Bannach
authors.initials: LB
authors.lastname: Jardim
mesh_terms: D000328:Adult; D017668:Age of Onset; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood*; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006579:Heterozygote; D006801:Humans; D017827:Machado-Joseph Disease / Q000097:blood* / Q000235:genetics; D008297:Male; D012720:Severity of Illness Index; D013997:Time Factors; D019680:Trinucleotide Repeat Expansion
chemical_list: D015415:Biomarkers; D016207:Cytokines
keywords: Cytokines; Discriminant analysis; Eotaxin; Machado Joseph disease; Neuroprotection; Spinocerebellar ataxia type 3