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MS is a heterogeneous disease either in its response to treatment or clinical manifestation. Indeed, the natural history of MS is varying from a benign condition to a devastating and rapidly incapacitating disease. Clinical heterogeneity could also be cellular and / or molecular. The aim is to identify from OMIC analyses, at the early stage of the disease, differentially expressed molecules and / or cell subpopulations derived from CD8 + T lymphocytes and / or CD4 + T lymphocytes and / or B lymphocytes and monocytes from patients with aggressive versus non-aggressive, compared to a cohort of healthy controls
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Retrospective Aggressive MS patients | Other | Patients from who the clinical outcome is already known and classified as poor based on study definition detailed in inclusion criteria (retrospective arm). Blood sample collected after first event is available and used to characterize OMIC profile of T and B cells involve in MS. |
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| Retrospective Non Aggressive MS patient | Other | Patient from who the clinical outcome is already known and classified as non-aggressive based on study definition detailed in inclusion criteria (retrospective arm). Blood sample collected after first event is available and used to characterize OMIC profile of T and B cells involve in MS. |
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| Healthy volunteers | Other | Prospective arm use as comparator. |
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| Prospective MS patients | Other | MS patients from who the clinical outcome will be established at the end of the follow up. Blood sample will be collected after the first event to validate molecules of interest from OMIC results by using FACS a different technology and classify MS patient. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Biological sample collection | Other | Venous blood sample will be collected from patients belonging to validation cohort and healthy volunteers at baseline resulting in 90 Ml EDTA tube and 10 ml serum tube. Approximately 100 ml will be collected. optional saliva and stool collection will be performed. |
| Measure | Description | Time Frame |
|---|---|---|
| Bulk RNA-sequencing | Transcriptional profile of T and B cells in aggressive and non-aggressive MS and healthy volunteers. Measurement of gene expression of naïve and memory CD4+ and CD8+ T and B cell. Comparison of these expression level between MS patients with aggressive and non-aggressive form and healthy volunteers. | Blood sample collection within 6 months after first inflammatory event for MS patients and at inclusion for healthy volunteers. |
| Measure | Description | Time Frame |
|---|---|---|
| Single RNA sequencing | Single cell transcriptomics of T and B cells in order to identify by clustering, sub populations within these cells based on gene expression and associated to poor pronostic. | Blood sample collection within 6 months after first inflammatory event. |
| Association of genetic sequence variation from whole genome sequencing with gene expression profile via Bulk RNA-seq |
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Inclusion Criteria :
Common criteria for retrospective MS patients:
Criteria for Aggressive MS group
• Start of a 2nd line therapy within the two years following the CIS
Criteria for Non aggressive MS group
Healthy volunteers
Pairing criteria :
Prospective MS Patients
Exclusion Criteria :
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| David LAPLAUD, PhD | Contact | 33 2 40 16 52 00 | david.laplaud@chu-nantes.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nantes University Hospital | Recruiting | Nantes | Loire-Atlantique | 44093 | France |
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| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
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The study model consists of two cohorts, the first one or "learning cohort" includes a group of health volunteers and 2 groups of MS patients from who clinical outcome (aggressive vs non-aggressive) is already known based on clinical follow up since first event. Clinical data and blood sample have been already collected and are available from OFSEP (Observatoire français de la Sclérose en plaques). Blood will be analyzed to characterize transcriptomic, epigenomic, genomic immune cells features to discover predictive markers of clinical outcome. The second cohort or "validation cohort" consists of MS patients enrolled after their first event and followed for maximum 2-years until the determination of their clinical outcome. Blood will be collected after their first event and used in FACS to classified the patients based on molecule of interest discover thanks to learning cohort and predict clinical outcome.
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|
Add genetic variant analyzes to RNA seq analyses related to MS 1) Identify eQTL. 2 Impute SNPs result to calculate MS Genetic Burden (MSGB) a polygenic risk score of MS computed based on a weighted scoring algorithm using independent MS-SNPs. |
| Blood sample collection within 6 months after first inflammatory event. |
| Association of transcriptomic variation with DNA methylation | Add Analyzes of gene expression regulation throughout DNA methylation of CpG sites to RNA seq analyses related to MS. | Blood sample collection within 6 months after first inflammatory event. |
| OMIC integration | Developing machine learning method to combine genomic, epigenomic transcriptomic and clinical data to pinpoint genes of interest particularly involved in aggressive MS outcomes. | Blood sample collection within 6 months after first inflammatory event. |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |