Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/2680
Title: Activation of the JAK-STAT Signaling Pathway after In Vitro Stimulation with IFNß in Multiple Sclerosis Patients According to the Therapeutic Response to IFNß
Authors: Hurtado-Guerrero, Isaac
Pinto-Medel, Maria Jesús
Urbaneja, Patricia
Rodriguez-Bada, Jose Luis
León, Antonio
Guerrero, Miguel
Fernández, Óscar
Leyva, Laura
Oliver-Martos, Begoña
metadata.dc.contributor.authoraffiliation: Unidad de Gestión Clínica de Neurociencias, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Universidad de Málaga, Málaga, Spain.
Keywords: Biomarcadores;Citometría de flujo;Humanos;Leucocitos mononucleares;Monocitos;Esclerosis múltiple;Fenotipo;Factor de Transcripción STAT1;Factor de Transcripción STAT2;Resultado del tratamiento
metadata.dc.subject.mesh: Medical Subject Headings::Chemicals and Drugs::Biological Factors::Biomarkers
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Cell Separation::Flow Cytometry
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Interferons::Interferon Type I::Interferon-beta::Interferon beta-1a
Medical Subject Headings::Chemicals and Drugs::Biological Factors::Intercellular Signaling Peptides and Proteins::Interferons::Interferon Type I::Interferon-beta
Medical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear
Medical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Monocytes
Medical Subject Headings::Diseases::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotype
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Adaptor Proteins, Signal Transducing::STAT Transcription Factors::STAT1 Transcription Factor
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Adaptor Proteins, Signal Transducing::STAT Transcription Factors::STAT2 Transcription Factor
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome
Issue Date: 19-Jan-2017
Publisher: Public Libray of Science
Citation: Hurtado-Guerrero I, Pinto-Medel MJ, Urbaneja P, Rodriguez- Bada JL, León A, Guerrero M, et al. Activation of the JAK-STAT Signaling Pathway after In Vitro Stimulation with IFNß in Multiple Sclerosis Patients According to the Therapeutic Response to IFNß. PLoS ONE. 2017: 12(1): e0170031.
Abstract: Interferon beta (IFNß) is a common treatment used for multiple sclerosis (MS) which acts through the activation of the JAK-STAT pathway. However, this therapy is not always effective and currently there are no reliable biomarkers to predict therapeutic response. We postulate that the heterogeneity in the response to IFNß therapy could be related to differential activation patterns of the JAK-STAT signaling pathway. Our aim was to evaluate the basal levels and the short term activation of this pathway after IFNß stimulation in untreated and IFNß treated patients, as well as according to therapeutic response. Therefore, cell surface levels of IFNAR subunits (IFNAR1 and IFNAR2) and the activated forms of STAT1 and STAT2 were assessed in peripheral blood mononuclear cells from MS patients by flow cytometry. Basal levels of each of the markers strongly correlated with the expression of the others in untreated patients, but many of these correlations lost significance in treated patients and after short term activation with IFNß. Patients who had undergone IFNß treatment showed higher basal levels of IFNAR1 and pSTAT1, but a reduced response to in vitro exposure to IFNß. Conversely, untreated patients, with lower basal levels, showed a greater ability of short term activation of this pathway. Monocytes from responder patients had lower IFNAR1 levels (p = 0.039) and higher IFNAR2 levels (p = 0.035) than non-responders just after IFNß stimulation. A cluster analysis showed that levels of IFNAR1, IFNAR2 and pSTAT1-2 in monocytes grouped 13 out of 19 responder patients with a similar expression pattern, showing an association of this pattern with the phenotype of good response to IFNß (p = 0.013). Our findings suggest that an activation pattern of the IFNß signaling pathway in monocytes could be associated with a clinical phenotype of good response to IFNß treatment and that a differential modulation of the IFNAR subunits in monocytes could be related with treatment effectiveness.
URI: http://hdl.handle.net/10668/2680
metadata.dc.relation.publisherversion: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0170031
metadata.dc.identifier.doi: 10.1371/journal.pone.0170031
ISSN: 1932-6203 (Online)
Appears in Collections:01- Artículos - Hospital Regional de Málaga
01- Artículos - IBIMA. Instituto de Investigación Biomédica de Málaga

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