Multiple Sclerosis
Conditions
Brief summary
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
Interventions
OTHERBiological sample collection
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.
Sponsors
Nantes University Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
NA/NO
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
: Common criteria for retrospective MS patients: * Patients aged 18 years or older * Clinical isolated syndrome (CIS) with or without dissemination in space * Patients affiliated to an appropriate health insurance Criteria for Aggressive MS group • Start of a 2nd line therapy within the two years following the CIS Criteria for Non aggressive MS group * No conversion according to McDonald criteria from clinical isolated syndrome to multiple sclerosis within 2 years or * Conversion based to McDonald criteria treated or not with first line disease modifying therapy within 2 years. * Have a minimum of least 2 years of follow-up. Healthy volunteers * Aged 18 years or older * No history of clinically isolated syndrome or MS Pairing criteria : * Age +/- 5 years * Sex Prospective MS Patients * Patients aged 18 years or older * Clinical isolated syndrome (CIS) with or without dissemination in space * Patients affiliated to an appropriate health insurance
Exclusion criteria
: * Ongoing participation to a another study * Refusal to genetic analyses * Immunosuppressive drug at the time of blood collection * Plasma exchange or corticosteroid treatment within the four weeks prior to blood sample * Adults under a legal protection regime (guardianship, trusteeship, judicial safeguard) * Pregnancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bulk RNA-sequencing | Blood sample collection within 6 months after first inflammatory event for MS patients and at inclusion for healthy volunteers. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Single RNA sequencing | Blood sample collection within 6 months after first inflammatory event. | 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. |
| Association of genetic sequence variation from whole genome sequencing with gene expression profile via Bulk RNA-seq | Blood sample collection within 6 months after first inflammatory event. | 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. |
| Association of transcriptomic variation with DNA methylation | Blood sample collection within 6 months after first inflammatory event. | Add Analyzes of gene expression regulation throughout DNA methylation of CpG sites to RNA seq analyses related to MS. |
| OMIC integration | Blood sample collection within 6 months after first inflammatory event. | Developing machine learning method to combine genomic, epigenomic transcriptomic and clinical data to pinpoint genes of interest particularly involved in aggressive MS outcomes. |
Countries
France
Contacts
CONTACTDavid LAPLAUD, PhD
Outcome results
None listed