Abstract Details

Title Effects of Smoke Exposure on the Course of Multiple Sclerosis I. Role of Indoleamine 2,3-Dioxygenase (IDO) Activity

Topic MS and Related Diseases

Presentation(s) P04 - (-)

Poster/Presentation
Number 135

Objective

Background BACKGROUND: Exposure to cigarette smoke is emerging as an environmental factor in MS contributing both to disease susceptibility and progression. IDO, an enzyme involved in tryptophan degradation to its metabolite kynurenine, plays an important role in immune tolerance induction.

Design/Methods DESIGN/METHODS: Time to conversion from clinically isolated syndrome (CIS) to clinically definitive MS (CDMS), and from relapsing-remitting MS to secondary progressive MS (SPMS) was evaluated in 73 and 92 patients respectively. Serum cotinine concentration as indicator of active smoking was determined by ELISA. Tryptophan and kynurenine concentrations in peripheral blood were measured by HPLC, and IDO mRNA expression by RT-PCR. Production of IL-6, IL-10, IL-13, IL-17, IL-22, IFN-?, TGF-?, and anti-MOG antibodies was assessed by ELISPOT, and CD4+CD25+Foxp3+ regulatory T cells (Treg) were measured by flow cytometry.

Results RESULTS: Smoker CIS patients demonstrated high risk of developing CDMS, and a shorter time to first relapse compared to non-smokers. Moreover, smokers were more likely to develop SPMS compared to non-smokers, and in a shorter period of time. No differences were observed between male and female patients. IDO activity was significantly decreased in patients who smoked, and serum cotinine concentration correlated inversely with IDO activity. Smoker patients showed significant increase in the number of IL-6, IL-13, IL-17, IL-22, and anti-MOG antibody producing cells, as well as a decrease in the number of Treg cells. No effects were observed on IL-10, IFN-? or TGF-? production.

Conclusions CONCLUSIONS: Activity of the IDO enzyme is decreased in smoking patients. This reduction in IDO-dependent immunosuppression could be responsible for the link observed between smoking and MS risk, as well as a more severe disease course.

Authors/Disclosures
Jorge D. Correale, MD (Institute for Neurological Research) PRESENTER	Dr. Correale has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Correale has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ROche. Dr. Correale 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. Correale 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. Correale 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. Correale has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Genzyme. The institution of Dr. Correale has received research support from Merck. The institution of Dr. Correale has received research support from Biogen. The institution of Dr. Correale has received research support from Novartis .
	No disclosure on file
Oscar Fernandez, MD (Hospital Carlos Haya)	No disclosure on file

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