RGD Reference Report - Characterization of immune cell subsets during the active phase of multiple sclerosis reveals disease and c-Jun N-terminal kinase pathway biomarkers. - Rat Genome Database

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Characterization of immune cell subsets during the active phase of multiple sclerosis reveals disease and c-Jun N-terminal kinase pathway biomarkers.

Authors: Ferrandi, C  Richard, F  Tavano, P  Hauben, E  Barbie, V  Gotteland, JP  Greco, B  Fortunato, M  Mariani, MF  Furlan, R  Comi, G  Martino, G  Zaratin, PF 
Citation: Ferrandi C, etal., Mult Scler. 2011 Jan;17(1):43-56. Epub 2010 Sep 20.
RGD ID: 6893496
Pubmed: PMID:20855355   (View Abstract at PubMed)
DOI: DOI:10.1177/1352458510381258   (Journal Full-text)

BACKGROUND: Autoimmune activation and deregulated apoptosis of T lymphocytes are involved in multiple sclerosis (MS). c-Jun N-terminal kinase (JNK) plays a role in T-cell survival and apoptosis. OBJECTIVES: The aim of this work was to investigate the role of the JNK-dependent apoptosis pathway in relapsing-remitting MS (RRMS). METHODS: The immunomodulatory effect of AS602801, a JNK inhibitor, was firstly evaluated on activated peripheral blood mononuclear cells (PBMCs) from healthy volunteers (HVs) and secondly in unstimulated purified CD4+, CD8+ and CD11b+ cells from RRMS patients and HVs. Moreover JNK/inflammation/apoptosis related genes were investigated in RRMS and HV samples. RESULTS: In activated PBMCs from HVs, we showed that AS602801 blocked T-lymphocyte proliferation and induced apoptosis. In RRMS CD4+ and CD8+ cells, AS602801 induced apoptosis genes and expression of surface markers, while in RRMS CD11b+ cells it induced expression of innate immunity receptors and co-stimulatory molecules. Untreated cells from RRMS active-phase patients significantly released interleukin-23 (IL-23) and interferon-gamma (IFN-gamma) and expressed less apoptosis markers compared to the cells of HVs. Moreover, gene expression was significantly different in cells from RRMS active-phase patients vs. HVs. By comparing RRMS PBMCs in the active and stable phases, a specific genomic signature for RRMS was indentified. Additionally, CASP8AP2, CD36, ITGAL, NUMB, OLR1, PIAS-1, RNASEL, RTN4RL2 and THBS1 were identified for the first time as being associated to the active phase of RRMS. CONCLUSIONS: The analysis of the JNK-dependent apoptosis pathway can provide biomarkers for activated lymphocytes in the active phase of RRMS and a gene expression signature for disease status. The reported results might be useful to stratify patients, thereby supporting the development of novel therapies.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
relapsing-remitting multiple sclerosis  IEP 6893496 RGD 
relapsing-remitting multiple sclerosis  ISOCD36 (Homo sapiens)6893496; 6893496 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cd36  (CD36 molecule)

Genes (Mus musculus)
Cd36  (CD36 molecule)

Genes (Homo sapiens)
CD36  (CD36 molecule (CD36 blood group))


Additional Information