Abstract Details

Title Correction of Non-Response to Interferon-beta in Multiple Sclerosis

Topic MS and Related Diseases

Presentation(s) P01 - (-)

Poster/Presentation
Number 203

Objective

Background BACKGROUND: Normal immune cells respond vigorously to IFNs. However, there is low-level or no response to IFN-beta in mononuclear cells (MNCs) from most patients with clinically active or progressive MS, before any therapy. During active MS, IFN-beta does not phosphorylate/activate the STAT1 transcription factor on Serine, preventing induction of some IFN-stimulated genes.

Design/Methods DESIGN/METHODS: MNCs from healthy controls and clinically stable, relapsing, and progressive MS were incubated with 160 U/ml IFN-beta-1b for 0-2 hours and assayed for phospho (P)-STAT1 transcription factors, and 0-2 days for MxA analysis. Parallel cultures primed cells with different doses of IFN-beta overnight and were then restimulated for comparison to baseline responses.

Results RESULTS: MNC from therapy-naive relapsing and progressive MS patients had low baseline P-Ser-STAT1 and MxA levels, but normal P-Tyr-STAT1. Responses to IFN priming were greatest in stable MS and healthy controls. Priming with IFN-beta in vitro induced phosphorylation of STAT1 on Tyr and Ser, reversed the endogenous defect in P-Ser-STAT1 during clinically active MS to normal levels, and also induced IFN-responsive genes in immune cells from patients with stable and active MS.

Conclusions CONCLUSIONS: Defective endogenous responses to IFN can be reversed in vitro. Personalized profiles of sensitivity to IFN may be used to predict and adjust response to IFN therapy.

Authors/Disclosures
Anthony Reder, MD (University of Chicago) PRESENTER	Dr. Reder has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Xuan Feng, PhD (The University of Chicago Medical Center)	The institution of Dr. Feng has received research support from BMS.

��ɫ��

��ɫ��