Dataset Information

A one year follow-up study of natural killer and dendritic cells activities in multiple sclerosis patients receiving glatiramer acetate (GA).

ABSTRACT:

Background

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease. It is thought to be mediated by CD4(+) Th1/Th17 cells. More recently, cells of the innate immune system such as dendritic cells (DCs) and natural killer (NK) cells have been in focus. Glatiramer acetate (GA) is an approved drug for treating MS patients.

Methodology/principal findings

In the current study we examined the activities of NK and DCs in nine relapsing remitting MS patients for up to one year after initiation of GA treatment. We observed that NK cells isolated from most of these patients have increased cytotoxic activity against K562 cells. Further analysis showed that the same NK cells lysed both autologous immature (i) and mature (m) DCs. In most patients this increased activity was correlated with increased NK cell activating cytotoxicity receptors such as NKp30, NKp44, NKp46 and NKG2D, and reduced expression of the inhibitory molecule CD158 on the surface of these NK cells. The expression of HLA-DR was increased on iDCs and mDCs in the majority of the patients, but no consistency was observed for the expression of HLA-I or HLA-E. Also, the co-stimulatory receptors CD80, CD83 or CD86 expression was down-regulated on iDCs and mDCs in most cases. Further, the expression of CCR6 was increased on mDCs at later time points of therapy (between 32-48 weeks).

Conclusions/significance

Our results are the first showing the effects of GA treatment on NK cells in MS patients, which may impact future use of this and other drugs to treat this disease.

SUBMITTER: Hoglund RA

PROVIDER: S-EPMC3632560 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

A one year follow-up study of natural killer and dendritic cells activities in multiple sclerosis patients receiving glatiramer acetate (GA).

Høglund Rune A RA Holmøy Trygve T Harbo Hanne F HF Maghazachi Azzam A AA

PloS one 20130422 4

<h4>Background</h4>Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease. It is thought to be mediated by CD4(+) Th1/Th17 cells. More recently, cells of the innate immune system such as dendritic cells (DCs) and natural killer (NK) cells have been in focus. Glatiramer acetate (GA) is an approved drug for treating MS patients.<h4>Methodology/principal findings</h4>In the current study we examined the activities of NK and DCs in nine relapsing remitting MS ...[more]

PMID: 23614042

Similar Datasets

Project description:BackgroundGlatiramer acetate (GA) is one of the first therapies approved for multiple sclerosis (MS). We prospectively included and monitored drug-naïve and pre-treated MS patients who had been prescribed GA for 1 year, to investigate reasons for GA prescription, its effectiveness and safety in real life clinical practice.MethodsOne year, prospective, multicentre, observational study performed between 2010 and 2015 in consecutive MS and clinically isolated syndrome patients starting GA as a first ("naïve") or second ("switcher") line therapy. Primary endpoint was the annualized relapse rate (ARR) over 1 year of GA treatment (from baseline, V1, to 12 months, V2) in naïve and switchers compared to previous 24 months. Secondary endpoints were: EDSS changes between V1 and V2, frequency of adverse events, and reasons for prescribing and discontinuing GA. Baseline demographics and clinical characteristics were retrieved from medical records, and outcome measures were documented at V1 and V2, and in case of clinical worsening.ResultsOne hundred ninety-four consecutive patients were monitored over 12 months (N = 64 naïve, N = 130 switchers). Side effect profile (naïve = 36%, switchers = 28%) and comorbidities (naïve = 31%, switchers = 15%) were the most frequent reasons to start GA. The ARR was reduced in both naïve and switchers during V1-2 as compared to the 24 months preceding V1 [naïve: 0.0 (0.0-0.0) vs 0.5 (0.5-1.0, p = 2.9e-10); switchers: 0.0 (0.0-0.0) vs 0.5 (0.0-0.5, p = 0.022)]. EDSS at V2 was significantly reduced only in naïve [(1.5 (1.0-2.5) vs 2.0 (1.5-2.5), p = 0.003)]. Naïve status and EDSS at V1 were negatively associated with EDSS change between V1-V2 in multivariable analysis (regression coefficient = - 0.436, p = 0.008, and regression coefficient = - 0.263, p = 6.18e-05, respectively). No new unexpected AE was reported.ConclusionIn our Swiss cohort, GA was prescribed mainly to naïve or switcher MS patients fearing interferon related side effects, with various comorbidities or considering pregnancy, and showed effectiveness and safety comparable with data of previous GA studies.

Dataset Information

A one year follow-up study of natural killer and dendritic cells activities in multiple sclerosis patients receiving glatiramer acetate (GA).

Background

Methodology/principal findings

Conclusions/significance

Publications

A one year follow-up study of natural killer and dendritic cells activities in multiple sclerosis patients receiving glatiramer acetate (GA).

Similar Datasets

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