Recent genome-wide association studies (GWAS) have successfully identified several gene loci associated with multiple sclerosis (MS) susceptibility, severity or interferon-beta (IFN-ß) response.
Moreover, we reported for the first time the beneficial effect of NLRC4 rs479333 G >C variant in MS progression and in the response to IFN-ß treatment.
Several observations suggest that the interferon system may be of interest in the study of MS development To investigate whether polymorphism in components of the IFN system and the JAK-STAT pathway influence susceptibility to MS, we performed a linkage analysis between polymorphic loci in or close to the IFN gamma, IFN gamma receptor, IFN alpha/beta receptor, JAK 1, STAT 1 and STAT 3 genes in 27 Swedish families with at least two members having MS. Tests for transmission disequilibrium and nonparametric linkage analysis gave negative results.
In French West Indies (FWI), where MS has arisen from the end of the 80's, a low therapeutic response to interferons beta1 (IFN beta1) in patients of African descent, restrains the therapeutic options.
Resultant N-terminal truncated IFN mimetics functioned intracellularly as antivirals as well as therapeutics against experimental allergic encephalomyelitis without the undesirable side effects that limit the therapeutic efficacy of IFNβ in treatment of multiple sclerosis.
To determine whether the therapeutic benefit of interferon-β (IFN-β) treatment for MS is in part influenced by IFN regulation of DC function, we examined the immunophenotype of DCs derived from IFN-β<sup>+/+</sup> and IFN-β<sup>-/-</sup> mice using a myelin oligodendrocyte glycoprotein (MOG) peptide-induced mouse model of MS, experimental autoimmune encephalomyelitis (EAE).
The aim of the present study was to determine the effect of interferon beta (IFN ß) on the metabolome of MS patients to explore possible biomarkers of disease activity and therapeutic response.
The FUTURE (Quality of liFe in adolescent sUbjecTs affected by mUltiple sclerosis treated with immunomodulatoRy agEnt using self-injecting device) study was designed to evaluate the changes in QL of Italian adolescents with RRMS receiving treatment with IFN-β1a (Rebif; 22 μg), administered subcutaneously three times weekly using the RebiSmart™ electronic autoinjection device over a 52-week period.
Furthermore, the transduction of IFN-ß to AdMSCs maintained and, in some cases, enhanced the functional properties of AdMSCs by ameliorating the symptoms of MS in EAE models and by decreasing indications of peripheral and central neuro-inflammation.
Here, we show that induction of human IFN-γ<sup>-</sup>IL-17A<sup>-</sup>Foxp3<sup>+</sup>CD4<sup>+</sup> T cells is inhibited in the presence of circulating exosomes from patients with MS.
We hypothesize that the molecular response to type I IFN identifies a pathogenetically distinct subset of MS patients whose disease is driven in part by innate immunity.
Treatment choices for pediatric MS include many disease-modifying therapies (DMT) that are currently being used for adult MS and these are interferon-β 1a/1b (IFN-β1a/1b), glatiramer acetate, teriflunomide, dimethyl fumarate, alemtuzumab, etc.
These data imply that the expression levels of IFN response genes in the peripheral blood of MS patients prior to treatment could serve a role as biomarker for the differential clinical response to IFNbeta.
This review discusses the role of OPN and IL-17 in the development of MS and how the downregulation of the levels of OPN and interleukin-17 contributes to the therapeutic effects of IFN-β in MS.
The observed alterations in the gene expression of molecules involved in the TLR4 and TLR7 signaling pathways in circulating DC subsets may underlie the impaired IL-12p70 and IFN-α secretion in patients with RRMS, thereby potentially contributing to the disease pathogenesis of MS.
In this review, IFN activity measurements will be discussed with a specific emphasis on what is known about differential gene expression and treatment effects in MS.
Identification of the synthetic cannabinoid R(+)WIN55,212-2 as a novel regulator of IFN regulatory factor 3 activation and IFN-beta expression: relevance to therapeutic effects in models of multiple sclerosis.
IFN-β1a decreased IL-17 and increased IL-10 seric levels; IL-17 significantly correlated with MS activity; TGF-β1 activity is titer-dependent, increased levels were associated with IL-17 inhibition; NR patients to IFN-β1a will have initial high IL-17 and low IL-10 and TGF-β seric levels.