好色先生

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Abstract Details

Corticosteroid Receptor Expression and In Vivo Glucocorticoid Sensitivity in Patients with Multiple Sclerosis
MS and Related Diseases
P05 - (-)
176
BACKGROUND: Patients with MS display chronic, subclinical hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis. Cross-sectional and longitudinal studies have described a correlation between HPA hyperactivity and clinical and magnetic resonance imaging variables. Further, in vitro assays suggested that glucocorticoid sensitivity is reduced in immune cells of MS patients.
DESIGN/METHODS: We measured the relative mRNA expression of the mineralocorticoid receptor (MR), glucocorticoid receptor (GR), and genes regulated by the GR: FK506 binding protein 5 (FKBP5), Glucocorticoid-induced Leucine Zipper (GILZ), Dual specificity phosphatase-1 (DUSP1) and nuclear factor ?B (NF-?B) in whole blood from 52 patients with multiple sclerosis and 18 healthy volunteers, using quantitative polymerase chain reaction.
RESULTS: Expression of GR and MR was significantly lower in MS patients than controls. Expression of the GR transcriptional targets FKBP5, GILZ and DUSP1 was higher in patients, reaching statistical significance for GILZ. The expression of NF-?B did not differ significantly between patients and controls. The expression of GR and MR decreased with increasing degree of disability (EDSS). GILZ was upregulated in MS patients with mild and moderate disability, while its expression declined in patients with severe disability even below that measured in the controls.
CONCLUSIONS: In MS patients with mild or moderate disability, immune cells appear to retain GC sensitivity despite reduced GR expression. We interpret GR reduction as a consequence of chronic HPA hyperactivity, compensated by as yet unidentified mechanisms. With progressing disease, GR is further reduced, while the compensatory mechanisms fail. This may contribute to a lack of physiological down-modulation of auto-immunity.
Authors/Disclosures

PRESENTER 		No disclosure on file
No disclosure on file
Muriel Stoppe Muriel Stoppe has nothing to disclose.
Peter B. Kang, MD, FAAN (University of Minnesota Medical School) Dr. Kang has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Neurogene. Dr. Kang has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lupin. Dr. Kang has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ITF Therapeutics (Italfarmaco). An immediate family member of Dr. Kang has received personal compensation in the range of $0-$499 for serving as a Consultant for Life Sciences Consultants. Dr. Kang has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MLAB Biosciences. Dr. Kang has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley. Dr. Kang has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for 好色先生. The institution of Dr. Kang has received research support from Xtraordinary Joy Foundation. The institution of an immediate family member of Dr. Kang has received research support from Sarepta Therapeutics. The institution of Dr. Kang has received research support from Centers for Disease Control and Prevention (CDC). The institution of Dr. Kang has received research support from National Institutes of Health (NIH). The institution of Dr. Kang has received research support from Food and Drug Administration. The institution of Dr. Kang has received research support from National Initiative for Cockayne Syndrome. The institution of Dr. Kang has received research support from Greg Marzolf Jr Foundation. The institution of Dr. Kang has received research support from Sarepta Therapeutics. The institution of Dr. Kang has received research support from Duchenne UK - PPMD. The institution of an immediate family member of Dr. Kang has received research support from Regenerative Medicine MN. The institution of an immediate family member of Dr. Kang has received research support from Greg Marzolf Jr Foundation. The institution of an immediate family member of Dr. Kang has received research support from NIH. The institution of an immediate family member of Dr. Kang has received research support from Viljem Julijan Association for Children with Rare Disease. The institution of Dr. Kang has received research support from Minnesota Partnership. Dr. Kang has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Kang has received intellectual property interests from a discovery or technology relating to health care. Dr. Kang has received publishing royalties from a publication relating to health care. Dr. Kang has a non-compensated relationship as a Medical Advisory Board with Speak Foundation that is relevant to AAN interests or activities. Dr. Kang has a non-compensated relationship as a President (Including President-Elect and Past President) with Child Neurology Society that is relevant to AAN interests or activities. Dr. Kang has a non-compensated relationship as a Board Member with Child Neurology Foundation that is relevant to AAN interests or activities.
Steffi Grey No disclosure on file
Barbara Ettrich 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.