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1.
Data Brief ; 11: 364-370, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28275670

RESUMO

The data presented in this article are related to the research article entitled "The autoimmune risk gene ZMIZ1 is a vitamin D responsived marker of a molecular phenotype of multiple sclerosis" Fewings et al. (2017) [1]. Here we identify the set of genes correlated with ZMIZ1 in multiple cohorts, provide phenotypic details on those cohorts, and identify the genes negatively correlated with ZMIZ1 and the cells predominantly expressing those genes. We identify the metabolic pathways in which the molecular phenotype genes are over-represented. Finally, we present the flow cytometry gating strategy we have used to identify the immune cells from blood which are producing ZMIZ1 and RPS6.

2.
J Autoimmun ; 78: 57-69, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28063629

RESUMO

Multiple Sclerosis (MS) is a neurological condition driven in part by immune cells from the peripheral circulation, the targets for current successful therapies. The autoimmune and MS risk gene ZMIZ1 is underexpressed in blood in people with MS. We show that, from three independent sets of transcriptomic data, expression of ZMIZ1 is tightly correlated with that of hundreds of other genes. Further we show expression is partially heritable (heritability 0.26), relatively stable over time, predominantly in plasmacytoid dendritic cells and non-classical monocytes, and that levels of ZMIZ1 protein expression are reduced in MS. ZMIZ1 gene expression is increased in response to calcipotriol (1,25 Vitamin D3) (p < 0.0003) and associated with Epstein Barr Virus (EBV) EBNA-1 antibody titre (p < 0.004). MS therapies fingolimod and dimethyl fumarate altered blood ZMIZ1 gene expression compared to untreated MS. The phenotype indicates susceptibility to MS, and may correspond with clinical response and represent a novel clinical target.


Assuntos
Autoimunidade/genética , Esclerose Múltipla/etiologia , Esclerose Múltipla/metabolismo , Fenótipo , Fatores de Transcrição/genética , Vitamina D/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Estudos de Casos e Controles , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Suscetibilidade a Doenças , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/imunologia , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Genótipo , Herpesvirus Humano 4/imunologia , Humanos , Padrões de Herança , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/metabolismo , Esclerose Múltipla/patologia , Polimorfismo de Nucleotídeo Único , Estações do Ano , Fatores de Transcrição/metabolismo , Vitamina D/farmacologia , Adulto Jovem
3.
Clin Exp Immunol ; 157(3): 365-9, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19664144

RESUMO

Common variable immunodeficiency (CVID) is a B cell immunodeficiency disorder characterized frequently by failure of memory B cell development and antibody secretion. A unifying cellular pathogenesis for CVID has not been forthcoming, but given the immunoregulatory role of invariant NK (iNK) T cells and their absence in several other immunodeficiencies, we quantified these cells in the blood of 58 CVID patients. There was a marked decrease in the proportion of iNK T cells in CVID patients compared with controls. This was particularly notable in those with low isotype-switched memory B cells, but subset analysis demonstrated no difference when stratified by specific clinical features. We propose that the decreased proportion of iNK T cells in CVID might be linked to the failure of memory B cell generation, which may contribute to reduced antibody production in these patients.


Assuntos
Imunodeficiência de Variável Comum/imunologia , Células T Matadoras Naturais/imunologia , Formação de Anticorpos , Linfócitos B/imunologia , Estudos de Casos e Controles , Criopreservação , Citometria de Fluxo , Humanos , Switching de Imunoglobulina , Memória Imunológica , Ativação Linfocitária , Contagem de Linfócitos , Estatísticas não Paramétricas , Fatores de Tempo
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