Abstract Details

Title Serum Cytokines, Neuroprotective Proteins, and Interferon Signaling in IFN Therapy Responders (R) and Non-Responders (NR) in MS

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 182

Objective

Background BACKGROUND: IFN responses are subnormal during active disease in most MS patients--before any therapy. Exacerbations could change IFN responses. IFNs induce more than 1000 genes, yet RNA and DNA biomarkers are not helpful in decision making during IFN therapy.

Design/Methods DESIGN/METHODS: In 28 R and NR to IFN-beta therapy, sera and MNC were collected after 60h drug washout (0h), and 4, 24, 48h after injection of 250, then later 500, mcg IFN-beta-1b during clinically stable MS (R, NR). More than 6mo later, injection was repeated with 500 mcg during clinical exacerbations in a paired subset of patients (NR by definition). 35 IFN signaling and serum proteins selected based on literature, RNA expression, and GWAS data that control response to therapy were measured for putative biomarkers by Western blots, serum IFN activity assay, and serum Luminex multiplex.

Results RESULTS: P-S-STAT1, MxA and other cytokines, and serum IFN-alpha/beta activity rose after 250 mcg injections, and were elevated further with 500 mcg IFN-beta. In vitro IFN signaling molecules and MxA decrease with exacerbations. Low levels of MxA and multiple IFN responses were reduced during clinically stable MS in patients who 6 mo later developed attacks. High-dose IFN induced certain proteins more than did low-dose IFN.

Conclusions CONCLUSIONS: IFN signaling in vitro, and in serum during therapy, reflect altered endogenous control of IFN responses, and this is dependent on disease activity. Profiling a combination of these biomarkers may predict attacks and may allow personalized therapy.

Authors/Disclosures
Xuan Feng, PhD (The University of Chicago Medical Center) PRESENTER	The institution of Dr. Feng has received research support from BMS.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Jan A. Hillert, MD (Karolinska Institute, Neurology R54)	Dr. Hillert has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Hillert has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Celgene. Dr. Hillert has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Hillert has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hillert has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sandoz. Dr. Hillert has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. The institution of Dr. Hillert has received research support from Biogen. The institution of Dr. Hillert has received research support from Celgene. The institution of Dr. Hillert has received research support from Merck. The institution of Dr. Hillert has received research support from Novartis. The institution of Dr. Hillert has received research support from Sanofi. The institution of Dr. Hillert has received research support from Roche.
	No disclosure on file
Anthony Reder, MD (University of Chicago)	Dr. Reder has nothing to disclose.

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