Contributions
Abstract: EP1482
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 15 Immunology
Background: CD4+Th17 cells play a predominant role on T cell-mediated immunity on Multiple Sclerosis (MS). Previously, we showed that SMAD7 and S1PR1 were differentially regulated in relapsing-remitting MS (RRMS) patients versus healthy donors (HD). SMAD family mediates signalling of the TGF-ß pathway, related to Th1/Th17 shift in autoimmune CNS inflammation. Sphingosine 1-phosphate regulates lymphocyte egress from lymphoid organs. To date, conflicting data about SMAD member's expression and S1PR1 have been described in RRMS. In Crohn's disease (CD), another autoimmune condition, SMAD7 is clearly upregulated in the gastrointestinal mucosa.
Objectives: To compare gene expression changes of SMAD members and S1PR1 in RRMS, compared to CD patients and HD.
Methods: PBMCs were purified by gradient density from 20 ml of fresh blood. CD4+ T lymphocytes were isolated by negative selection and magnetic separation. RNA was isolated from CD4+ T cells and cDNA transcribed. SMAD2, SMAD3, SMAD4, SMAD7 and S1PR1 genes were quantified by qRT-PCR in 20 HD, 20 RRMS patients without disease activity, 40 RRMS patients during a relapse, and 20 CD patients on active relapse. False discovery rate corrected by Benjamini-Hochberg was calculated for comparisons between groups.
Results: Compared to HD, we found SMAD7 and SMAD3 were underexpressed in stable RRMS patients (-3.2x-fold and -1.4x-fold, respectively). SMAD7 (-2.4x-fold), SMAD4 (-1.2x-fold) and S1PR1 (-1.4x-fold) were downregulated in RRMS patients during a relapse. Finally, all analyzed genes were downregulated in active CD patients (SMAD7, -4.8x-fold; SMAD4, -1.7x-fold; SMAD3 -1.9x-fold; SMAD2, -1.3x-fold and S1PR1, -1.7x-fold).
Conclusions: Transcription of SMAD family members and S1PR1 gene is lower in RRMS patients during both relapsing and remitting phases, and in active Crohn disease patients.
Disclosure: Work with funding by Genzyme, as Young Investigator´s Award 2015
Abstract: EP1482
Type: ePoster
Abstract Category: Pathology and pathogenesis of MS - 15 Immunology
Background: CD4+Th17 cells play a predominant role on T cell-mediated immunity on Multiple Sclerosis (MS). Previously, we showed that SMAD7 and S1PR1 were differentially regulated in relapsing-remitting MS (RRMS) patients versus healthy donors (HD). SMAD family mediates signalling of the TGF-ß pathway, related to Th1/Th17 shift in autoimmune CNS inflammation. Sphingosine 1-phosphate regulates lymphocyte egress from lymphoid organs. To date, conflicting data about SMAD member's expression and S1PR1 have been described in RRMS. In Crohn's disease (CD), another autoimmune condition, SMAD7 is clearly upregulated in the gastrointestinal mucosa.
Objectives: To compare gene expression changes of SMAD members and S1PR1 in RRMS, compared to CD patients and HD.
Methods: PBMCs were purified by gradient density from 20 ml of fresh blood. CD4+ T lymphocytes were isolated by negative selection and magnetic separation. RNA was isolated from CD4+ T cells and cDNA transcribed. SMAD2, SMAD3, SMAD4, SMAD7 and S1PR1 genes were quantified by qRT-PCR in 20 HD, 20 RRMS patients without disease activity, 40 RRMS patients during a relapse, and 20 CD patients on active relapse. False discovery rate corrected by Benjamini-Hochberg was calculated for comparisons between groups.
Results: Compared to HD, we found SMAD7 and SMAD3 were underexpressed in stable RRMS patients (-3.2x-fold and -1.4x-fold, respectively). SMAD7 (-2.4x-fold), SMAD4 (-1.2x-fold) and S1PR1 (-1.4x-fold) were downregulated in RRMS patients during a relapse. Finally, all analyzed genes were downregulated in active CD patients (SMAD7, -4.8x-fold; SMAD4, -1.7x-fold; SMAD3 -1.9x-fold; SMAD2, -1.3x-fold and S1PR1, -1.7x-fold).
Conclusions: Transcription of SMAD family members and S1PR1 gene is lower in RRMS patients during both relapsing and remitting phases, and in active Crohn disease patients.
Disclosure: Work with funding by Genzyme, as Young Investigator´s Award 2015