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Cell-specific effects in different immune subsets associated with SOCS1 genotypes in multiple sclerosis.
Lopez de Lapuente, Aitzkoa; Pinto-Medel, María Jesús; Astobiza, Ianire; Alloza, Iraide; Comabella, Manuel; Malhotra, Sunny; Montalban, Xavier; Zettl, Uwe K; Rodríguez-Antigüedad, Alfredo; Fernández, Oscar; Vandenbroeck, Koen.
Afiliação
  • Lopez de Lapuente A; Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Spain/Achucarro Basque Center for Neuroscience, Spain.
  • Pinto-Medel MJ; Research Laboratory, Clinical Neurosciences Institute, Hospital Regional Universitario Carlos Haya and Fundación IMABIS.
  • Astobiza I; Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Spain/Achucarro Basque Center for Neuroscience, Spain.
  • Alloza I; Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Spain/ Achucarro Basque Center for Neuroscience, Spain/ IKERBASQUE, Basque Foundation for Science, Spain.
  • Comabella M; Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain.
  • Malhotra S; Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain.
  • Montalban X; Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain.
  • Zettl UK; University of Rostock, Department of Neurology, Germany.
  • Rodríguez-Antigüedad A; Servicio de Neurología, Hospital de Basurto, Spain.
  • Fernández O; Research Laboratory, Clinical Neurosciences Institute, Hospital Regional Universitario Carlos Haya and Fundación IMABIS.
  • Vandenbroeck K; Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Spain/ Achucarro Basque Center for Neuroscience, Spain/ IKERBASQUE, Basque Foundation for Science, Spain k.vandenboeck@ikerbasque.org.
Mult Scler ; 21(12): 1498-512, 2015 Oct.
Article em En | MEDLINE | ID: mdl-25623250
ABSTRACT

BACKGROUND:

Single nucleotide polymorphisms (SNPs) near SOCS1 are associated with multiple sclerosis (MS), but the most important SNPs in the area and mechanisms by which they influence the disease are unknown.

METHODS:

A haplotype-tagging association study was performed covering 60.5kbp around SOCS1, and the index SNP was validated in a total of 2292 individuals. mRNA expression of SOCS1 and nearby genes was measured in MS patients with different disease courses and healthy controls. SOCS1 protein expression was studied by flow cytometry in a separate cohort of patients and controls. Differentiation and maturation of monocyte-derived dendritic cells (moDCs) were also studied.

RESULTS:

One SNP, rs423674, reached genome-wide significance. No genotype-specific mRNA expression differences were seen, but, by flow cytometry, significant interactions were observed between genotypes for rs423674 and disease activity (relapse or remission) in B cells and regulatory T cells. Furthermore, homozygotes for the risk allele (GG) showed higher levels of CD1a and CD86 than carriers of the protective allele (GT) in immature moDCs and a greater increase of HLA-DR+ cell percentage than GT heterozygotes upon maturation.

CONCLUSIONS:

rs423674, or its genetic proxies, may influence MS risk by modulating SOCS1 expression in a cell-specific manner and by influencing dendritic cell function.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Dendríticas / Expressão Gênica / Esclerose Múltipla Recidivante-Remitente / Proteínas Supressoras da Sinalização de Citocina Idioma: En Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Células Dendríticas / Expressão Gênica / Esclerose Múltipla Recidivante-Remitente / Proteínas Supressoras da Sinalização de Citocina Idioma: En Ano de publicação: 2015 Tipo de documento: Article