EPIC: Epigenetic Evaluation of HAT/HDAC Activity in PBMC From Patients With Clinically Isolated Syndrome
Study Details
Study Description
Brief Summary
The aim of the study is to compare the enzymatic activity of HATs and HDACs in peripheral blood mononuclear cell (PBMC) of patients with a clinically isolated syndrome (CIS group) and healthy controls (control group).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
Detailed Description
Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS). Clinically isolated syndrome (CIS) is often a sign of multiple sclerosis and the term refers to the first episode of neurologic symptoms experienced by a patient. Possible presentations of CIS include optic neuritis, a brain stem and/or cerebellar syndrome, a spinal cord syndrome, or occasionally cerebral hemispheric dysfunction. An accurate diagnosis at this time is important because people with a high risk of developing MS are encouraged to begin treatment in order to delay or prevent a second neurologic episode and, therefore, the onset of MS.
The innate and adaptative immune systems play an important role in pathophysiology of MS, acting in interaction with environmental, genetic, and epigenetic factors.
Epigenetic modifications, such as DNA methylation and histone modification, alter DNA accessibility and chromatin structure, thereby regulating patterns of gene expression. These processes are crucial to normal development and differentiation of distinct cell lineages in the adult organism. Histone acetylation, through the family of histone acetyl transferase (HAT), is most consistently associated with promoting transcription. Deacetylation of histones correlates with CpG methylation and the inactive state of chromatin. There are 4 classes of histone deacetylase enzymes (HDACs), with members capable of deacetylation of histones and/or other protein targets. Acetylation homeostasis is a key regulator of both immune cell activation. Of note, potent histone deacetylase inhibitors (HDACi) endowed with antiinflammatory and neuroprotective properties have been identified. Efficacy of HDACi in experimental models of MS has been reported consistently. This study could provide information on the mechanisms involved.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Control group Healthy volunteers, free of any inflammatory disease. A blood sample is performed on the day of inclusion. |
Biological: blood sample
|
| Experimental: CIS group patients with Clinically isolated syndrome. A blood sample is performed on the day of inclusion and after 3 months. |
Biological: blood sample
|
Outcome Measures
Primary Outcome Measures
- HDAC/ HAT enzymatic activity (ratio) [day of inclusion]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Clinically isolated syndrome within the last 6 weeks (CIS group)
-
Healthy volunteer, free of any inflammatory disease (control group)
-
Patient able to understand the reason of the study
-
Signed informed consent
Exclusion Criteria:
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Pregnancy
-
Systemic corticosteroid therapy (>1mg/kg)
-
Immunosuppressive/immunomodulatory therapy (prior or ongoing) (CIS group)
-
Patient with ongoing infection (Control group)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital | Besançon | France |
Sponsors and Collaborators
- Centre Hospitalier Universitaire de Besancon
Investigators
- Principal Investigator: Matthieu Béreau, MD, CHU de Besançon
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- API/2015/64