Contributions
Abstract: EP1560
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: The hypothalamo-pituitary-adrenal axis (HPA axis) is activated in multiple sclerosis (MS) patients (Then Bergh et al. 1999; Gold et al. 2005), apparently related to disease course and progression. Our group showed in a cross-sectional study that gluco-(GR) and mineralocorticoid receptors (MR) are significantly downregulated in MS patients compared to healthy subjects (Bechmann, L et al. 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).
Objective: To investigate the longitudinal development of GR, MR and their target genes´ expression in MS and potential effects of disease-modifying treatment.
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 the initiation of steroid treatment) with that in patients 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 MS patients in remission (n=11). This finding allows us to analyze the longitudinal data without excluding patient data collected close to a relapse. Preliminary longitudinal analysis based on the first 100 patients with varying follow-up periods showed a rather abrupt, significant and lasting downregulation of the MR in patients treated with fingolimod (n=39; 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.
Disclosure: CG, FK, JO and AU have nothing to disclose. MS has received financial support, through her institution, to attend scientific meetings or for investigator initiated studies from Biogen, Fresenius, Merck Serono, Novartis, Sanofi Genzyme and Teva. SH has received financial support, through her institution, to attend scientific meetings from Bayer and Merck. FTB has received personal compensation for speaking and attending advisory boards from Actelion, Bayer, Biogen, Genzyme, Merck, Novartis, Teva and Roche; financial support, through his institution, to attend scientific meetings or for investigator initiated studies from Actelion, Bayer, Biogen, Genzyme, Merck, Novartis and Teva.
Abstract: EP1560
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: The hypothalamo-pituitary-adrenal axis (HPA axis) is activated in multiple sclerosis (MS) patients (Then Bergh et al. 1999; Gold et al. 2005), apparently related to disease course and progression. Our group showed in a cross-sectional study that gluco-(GR) and mineralocorticoid receptors (MR) are significantly downregulated in MS patients compared to healthy subjects (Bechmann, L et al. 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).
Objective: To investigate the longitudinal development of GR, MR and their target genes´ expression in MS and potential effects of disease-modifying treatment.
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 the initiation of steroid treatment) with that in patients 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 MS patients in remission (n=11). This finding allows us to analyze the longitudinal data without excluding patient data collected close to a relapse. Preliminary longitudinal analysis based on the first 100 patients with varying follow-up periods showed a rather abrupt, significant and lasting downregulation of the MR in patients treated with fingolimod (n=39; 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.
Disclosure: CG, FK, JO and AU have nothing to disclose. MS has received financial support, through her institution, to attend scientific meetings or for investigator initiated studies from Biogen, Fresenius, Merck Serono, Novartis, Sanofi Genzyme and Teva. SH has received financial support, through her institution, to attend scientific meetings from Bayer and Merck. FTB has received personal compensation for speaking and attending advisory boards from Actelion, Bayer, Biogen, Genzyme, Merck, Novartis, Teva and Roche; financial support, through his institution, to attend scientific meetings or for investigator initiated studies from Actelion, Bayer, Biogen, Genzyme, Merck, Novartis and Teva.