PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 16388356

Treatment optimisation in multiple sclerosis.

M Zaffaroni
View original source ↗Export metadata ↓

Abstract

Not all patients with multiple sclerosis (MS) respond equally to available disease modifying agents (DMA). Rational and reliable criteria are needed to identify responders and non responders in order to optimize the treatment. Natural history of the disease, clinical evolution and magnetic resonance imaging are the putative indicators to be considered with this respect, but neutralizing antibodies, possible immunological markers and pathological or genetic diversity may also represent future additional indicators. Clinical recommendations and consensus criteria for defining a suboptimal response to DMA have been proposed by different international panels of experts, but all need validation in experimental settings to provide solid guidelines for establishing when and how to take action on MS treatment with DMA.

Explore related subjects

Adjuvants, ImmunologicDecision Support TechniquesDisability EvaluationHumansMagnetic Resonance ImagingMultiple SclerosisPractice Guidelines as TopicTreatment OutcomeJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

M Zaffaroni. 2005. Treatment optimisation in multiple sclerosis.. https://doi.org/10.1007/s10072-005-0513-7

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Immunostimulatory RNA oligonucleotides trigger an antigen-specific cytotoxic T-cell and IgG2a response.

Single-stranded RNA oligonucleotides containing an immunostimulatory motif (immunostimulatory RNA [isRNA]) are potent inducers of interferon-alpha via the Toll-like receptor 7. We investigated the effect of isRNA on the development of an immune response. We show that isRNA activates dendritic cells and induces production of Th1-type cytokines both in vitro and in vivo. Cytokine production led to bystander activation of T and B cells. We further demonstrate that isRNA triggers the generation of antigen-specific cytotoxic T cells and of an IgG2a-biased antibody response to antigen in a sequence-dependent manner. In summary, we provide evidence for the first time that isRNA oligonucleotides can simultaneously activate the innate and adaptive arms of the immune system.

Adjuvants, Immunologic↗
PubMed2007

Mechanism of third signals provided by IL-12 and OX-40R ligation in eliciting therapeutic immunity following dendritic-tumor fusion vaccination.

Dendritic-tumor heterokaryons generated by electrofusion are highly immunogenic. In animal studies, a single vaccination was therapeutic for tumors established in the lung, skin, and brain. However, effective therapy required a third signal which could be provided by exogenous IL-12 or the agonistic anti-OX-40R monoclonal antibody (mAb). In this study, we investigated the mechanism and mode of actions of these two seemingly distinct adjuvants. In immunotherapy of the MCA205 sarcoma, administration of the neutralizing anti-IL-12 mAb nearly completely blocked the adjuvant effect of IL-12, but had minimal inhibitory effects on anti-OX-40R mAb. By contrast, in vivo administration of the antagonistic anti-OX-40L mAb inhibited the adjuvant effects of both IL-12 and anti-OX-40R mAb. Thus, a common pathway of endogenous OX-40 interaction is critical for the development of a therapeutic immune response. Analysis of the third signal mechanism revealed that in the absence of an adjuvant, vaccination with fusion hybrids led to IL-10 production without eliciting IFN-gamma secreting cells. The addition of IL-12 to vaccination suppressed IL-10 production and initiated sensitization of specific IFN-gamma secreting cells, resulting in a type 1-like antitumor immunity. These findings underscore the significance of the third signal in the design of dendritic cell-based cancer vaccines.

Adjuvants, Immunologic↗