Abstract Details

Title Immunomodulatory Treatment Strategies Differently Affect Dendritic Cells in Multiple Sclerosis Patients

Topic MS and Related Diseases

Presentation(s) S11 - (-)

Poster/Presentation
Number 006

Objective

Background Antigen presenting cells (APC) are directly involved in the MS pathogenesis. In addition to T and Bcells, immunomodulatory therapies exert effects on APC, especially DC. Modulation of DC function by MS treatment could elucidate indirect effects on different T cell populations, proinflammatory or regulatory. The most frequent DC in human blood is the slanDC, a well characterized proinflammatory DC.

Design/Methods SlanDC, CD1c+DC and monocytes of healthy controls, untreated MS-patients and treated MS-patients with interferon-beta, glatiramer acetate, natalizumab, fingolimod, teriflunomide, dimethyl-fumarate and laquinimod were analysed regarding their frequency, activation and maturation markers and pro-inflammatory cytokine release after stimulation with TLR-ligands by FACS analysis or ELISA. In vitro analysis was used to investigate capacity of pretreated DC to induce T cell responses.

Results SlanDC, CD1c+DC and monocytes did not differ in cell frequency or pro-inflammatory cytokine release in untreated MS-patients or healthy controls. In Interferon-beta treated patients, the frequency of slan-DC, but not of CD1c+DC and monocytes was significantly reduced. Beside decrease of TNF-a, IL-6 and IL-1b, Interferon-beta inhibited in vitro CD4+ and CD8+ T-cell proliferation and activation of naive CD4+T-cells. Fingolimod-treatment lead to a relative increase of slanDC and monocytes, impaired pro-inflammatory cytokine-secretion and induction of interferon-gamma-producing Th1-cells after LPS-stimulation. In dimethy-fumarate and teriflunomide-treated patients, inflammatory cytokine release of slanDC was decreased whereas slanDC frequency was decreased only in dimethyl-fumarate.-treated patients. In Laquinimod-treated patients, slanDC frequency and activation was significantly reduced. In contrast, treatment with natalizumab exerted no effects to the innate immune system.

Conclusions As slanDCs are key-players in MS pathology, treatment strategies focussed on slanDCs can be favourable modulating T cell effector responses.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Bianca Weinstock-Guttman, MD (Department of Neurology, University At Buffalo)	Dr. Weinstock-Guttman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis . Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme &Sanofi. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen . Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen. Dr. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving as a Reviewer with NIH.

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