Abstract Details

Title Longitudinal Expression of Gluco- and Mineralocorticoid Receptors and their Targets in Multiple Sclerosis

Topic Multiple Sclerosis

Presentation(s) P2 - Poster Session 2 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-087

Objective To investigate the longitudinal development of GR, MR and their target genes´ expression in MS, and potential effects of disease-modifying treatment.

Background The hypothalamo-pituitary-adrenal axis is activated in multiple sclerosis (MS; Then Bergh 1999; Gold 2005), apparently related to disease course and progression. Gluco-(GR) and mineralocorticoid receptors (GR) are significantly downregulated in MS patients compared to healthy subjects (Bechmann 2014). Downstream target genes of the GR were differentially up- or downregulated according to disease severity. We meanwhile identified bona-fide MR target genes in PBMC (Kuestermann et al., in preparation).

Design/Methods Using qPCR technique with total RNA isolated from lysed whole blood, we first compared the mRNA expression of GR, MR and selected downstream targets in MS patients during a relapse (before initiation of steroid treatment) with that in remission. Second, we analyzed the expression of these genes in blood samples taken over a period of up to five years, normalized to a baseline value measured before the initiation of the specific treatment. These patients are characterized demographically, clinically and according to disease modifying therapy.

Results Expression of GR, MR and their target genes´ mRNAs did not differ between MS patients during relapse (n=11) and those of matched patients in remission (n=11). This finding allows us to analyze the longitudinal data without excluding data collected close to a relapse. Longitudinal analysis in 128 patients with varying follow-up periods showed gradual, moderate increase of GR in patients treated with IFN beta (n=21), DMF (n=11) and fingolimod (n=34), and an abrupt, lasting downregulation of MR with fingolimod (up to 30 +/-2 months; p <0.0001).

Conclusions MS relapse does not significantly influence the expression of GR, MR and their target genes. DMT does affect the expression of some of these genes, possibly offering additional explanations of their modes of action, and/or additional options for treatment surveillance.

Authors/Disclosures
Clemens Goedel, MD (University Hospital Leipzig) PRESENTER	Dr. Goedel has nothing to disclose.
	No disclosure on file
Muriel Stoppe	Muriel Stoppe has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Florian Then Bergh, MD (University of Leipzig, Klinik u. Poliklinik fuer Neurologie)	Dr. Then Bergh 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. Then Bergh 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. Then Bergh 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. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Horizon. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Actelion. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genzyme. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Fresenius. Dr. Then Bergh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Merck. Dr. Then Bergh has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda. The institution of Dr. Then Bergh has received research support from Actelion. The institution of Dr. Then Bergh has received research support from Novartis. The institution of Dr. Then Bergh has received research support from DFG (German Science Fund). The institution of Dr. Then Bergh has received research support from Fresenius. The institution of Dr. Then Bergh has received research support from Diamed. Dr. Then Bergh has received personal compensation in the range of $10,000-$49,999 for serving as a Member of the Institutional Ethics Board with University of Leipzig, Medical Faculty.

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