Contributions
Abstract: P864
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Objectives: We aimed at applying systems medicine approaches combining integrative omics, imaging and clinical data with computational tools, to develop personalized healthcare for people with MS.
Methods: We recruited a prospective cohort of 329 MS patients and 90 healthy controls (HC). At baseline, we collected clinical information (demographics, relapses, disability scales and use of disease modifying drugs (DMD)), and imaging data (brain magnetic resonance imaging (MRI) and optical coherence tomography (OCT)). We conducted a multi-omics study including genotyping (Illumina OmniExpress chip comprising half million markers used to impute 152 MS-associated SNPs and 17 HLA-class II alleles and calculating the MS genetic burden score (MSGB)), cytomics (17 antibodies covering 11 subpopulations of T, B and NK cells) and phosphoproteomics (in vitro assays in peripheral blood mononuclear cells (PBMCs) with 3 time points (0, 10 and 30 min) and readout by xMAP assays with antibodies for 20 kinases).
Results: The patient cohort has the following characteristics at baseline: n= 328; age 41+10 years; sex: 71% female; duration: 10+8 years; subtype: 271 RRMS; 57 PMS; EDSS: median 2.0 (0-8.0); MSSS: 3.6+2.2; DMD: no therapy: 30%; platform/first line therapy 44%, high efficacy therapy: 26%); MRI: number of gadolinium lesions 0.1+0.5; T2 lesion volume: 8.17+10.5 cm3; (normalized) brain volume 1,509+91; grey matter volume 792+65 and white matter volume 716+68 cm3. The MSGB was significantly higher in patients compared with controls: MSGB: MS 4.23 vs HC 3.2 (p=3.4x10-8), MSGBHLA: MS 1.57 vs HC 0.95 (p=1.6x10-4), MSGBnon-HLA: MS 2.6 vs HC 2.2 (p=6.8x10-5). Regarding differences in immune cells subpopulations we found significant differences in patients compared with controls for regulatory T and B cells. Phosphoproteomics analysis and signaling pathways modeling pointed to an over-activation of the MAPK and NFKB pathways in patients with MS.
Conclusions: our results show significant differences between patients and HC at different scales of biological systems. Such markers will be used for searching prognostic and predictive biomarkers and developing clinical decision support systems for improving disease management.
Disclosure: This work was supported by the European Commission, ERACOSYSMED program (Sys4MS project). PV is currently an employe of Genentech. All other co-authors has not disclosures related with this study
Abstract: P864
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Objectives: We aimed at applying systems medicine approaches combining integrative omics, imaging and clinical data with computational tools, to develop personalized healthcare for people with MS.
Methods: We recruited a prospective cohort of 329 MS patients and 90 healthy controls (HC). At baseline, we collected clinical information (demographics, relapses, disability scales and use of disease modifying drugs (DMD)), and imaging data (brain magnetic resonance imaging (MRI) and optical coherence tomography (OCT)). We conducted a multi-omics study including genotyping (Illumina OmniExpress chip comprising half million markers used to impute 152 MS-associated SNPs and 17 HLA-class II alleles and calculating the MS genetic burden score (MSGB)), cytomics (17 antibodies covering 11 subpopulations of T, B and NK cells) and phosphoproteomics (in vitro assays in peripheral blood mononuclear cells (PBMCs) with 3 time points (0, 10 and 30 min) and readout by xMAP assays with antibodies for 20 kinases).
Results: The patient cohort has the following characteristics at baseline: n= 328; age 41+10 years; sex: 71% female; duration: 10+8 years; subtype: 271 RRMS; 57 PMS; EDSS: median 2.0 (0-8.0); MSSS: 3.6+2.2; DMD: no therapy: 30%; platform/first line therapy 44%, high efficacy therapy: 26%); MRI: number of gadolinium lesions 0.1+0.5; T2 lesion volume: 8.17+10.5 cm3; (normalized) brain volume 1,509+91; grey matter volume 792+65 and white matter volume 716+68 cm3. The MSGB was significantly higher in patients compared with controls: MSGB: MS 4.23 vs HC 3.2 (p=3.4x10-8), MSGBHLA: MS 1.57 vs HC 0.95 (p=1.6x10-4), MSGBnon-HLA: MS 2.6 vs HC 2.2 (p=6.8x10-5). Regarding differences in immune cells subpopulations we found significant differences in patients compared with controls for regulatory T and B cells. Phosphoproteomics analysis and signaling pathways modeling pointed to an over-activation of the MAPK and NFKB pathways in patients with MS.
Conclusions: our results show significant differences between patients and HC at different scales of biological systems. Such markers will be used for searching prognostic and predictive biomarkers and developing clinical decision support systems for improving disease management.
Disclosure: This work was supported by the European Commission, ERACOSYSMED program (Sys4MS project). PV is currently an employe of Genentech. All other co-authors has not disclosures related with this study