RESEPTOR 5-HT7 : Interest of the 5-HT7 Serotonin Receptor as a Biomarker in Multiple Sclerosis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- 5-HT7 receptor expression on circulating cells
研究概览
简要总结
Multiple Sclerosis is a chronic autoimmune disease associated with inflammatory response harmful for the Central Nervous System. Immunological imbalance is involved with Th1 and Th17 cells in correlation with a disturbance of regulators mechanisms as Treg cells. Despite years of research, the mechanisms involved remain unclear.
Serotonin (5-HT) seems to be play an essential role in developing CNS inflammatory diseases and in particular in MS. Indeed, several studies have shown the anti-inflammatory potential of this neurotransmitter and also its vulnerability in inflammatory context. Moreover, a recent study has shown that 5-HT can reduced CD4 T cells proliferation and pro-inflammatory cytokines released in vitro. Interestingly, treatment, treatment with SSRIs (selective serotonin reuptake inhibitor) in an animal model of MS, on Experimental Autoimmune Encephalomyelitis, was shown to improve the clinical score and promote remission of the disease.
Among serotonin receptors, the 5-HT7 receptor, can be considered as an interesting target to treat neurological disorders associated with inflammatory context. Present in humans and mice, this receptor is expressed on the surface of a large number of cells, such as T-lymphocytes, macrophages, dendritic cells as well as on cells of CNS such as neurons, astrocytes and microglia.
Given the importance of the positive cells for 5-HT7 receptor, in the inflammatory context observed in multiple sclerosis, the investigators propose to study the receptor expression in blood samples from multiple sclerosis patient.
详细描述
In a previous translational study (5-HT SEP), the expression modulation of 5-HT7 receptor in function of immunological context was investigated, in different group of MS patients:
- Group 1: MS patients with an acute relapse
- Group 2: MS stable patients treated with Natalizumab
- Group 3: Healthy people (from Etablissement Français du Sang) From blood cells of different groups of individuals, the investigators determined the percentage and intensity of expression of the receptor on circulating lymphocytes by flow cytometry.
The investigators demonstrated in this first study that the 5-HT7 receptor is mainly expressed on the surface of B lymphocytes compared to T lymphocytes.
Interestingly, while the percentage of T lymphocytes (CD4+, CD8+) remained unchanged between the 3 groups, the investigators observed that the expression of R5-HT7 on the surface of the T lymphocyte subpopulations (Th1, Th2, Th17 and Treg), is significantly increased in the blood of MS patients treated with Natalizumab compared to healthy individuals and MS patients in relapse.
Considering litterature data and our preliminary results showing the therapeutic potential of 5-HT7R ligand in animal models of MS as well as the upregulation of 5-HT7 expression in NTZ-treated patients (5-HTSEP study), the investigators wish to go further with these investigations. The main objective of this new translational study is to demonstrate the interest of the 5-HT7 serotonin receptor as a biomarker in the therapeutic monitoring of patients suffering from Multiple Sclerosis.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women
- •Aged between 18 and 50 years old,
- •With multiple sclerosis already diagnosed and fulfilling the modified Mc Donald criteria
- •Stable (no relapse in the last 6 months and MRI less than a year old, with no new lesions) and with at least 1 year of treatment with Natalizumab, Ocrelizumab, Teriflunomide or Fumarate
- •Subject medically fit to give a maximum of 50 ml of extra whole blood
- •Patient having given their consent to participate in the study
排除标准
- •HIV serology known or discovered during the present episode
- •Demented patient
- •Patient treated with corticosteroids in the last month
- •Non-affiliated person or non-beneficiary of a social security scheme
- •Uncooperative patient
- •Patient under legal protection, guardianship or curatorship
- •Pregnant or breastfeeding women
研究组 & 干预措施
Healthy individuals
Group 1: Healthy individuals, so-called "control" donors whose blood samples will be collected from the EFS (French Blood Establishment)
干预措施: Blood sample (Biological)
Stable MS patients treated with high efficacy treatment
Group 2: Stable MS patients without inflammatory activity of the disease treated with high efficacy treatment (Natalizumab or Ocrelizumab)
干预措施: Blood sample (Biological)
Stable MS patients treated with moderately effective treatment
Group 3: Stable MS patients without inflammatory disease activity treated with moderately effective treatment (Teriflunomide or Fumarate)
干预措施: Blood sample (Biological)
结局指标
主要结局
5-HT7 receptor expression on circulating cells
时间窗: Day 1
using the flow cytometry technique, on whole blood, we will perform immunophenotyping in order to determine the fluorescence intensity of cells positive for the receptor (5-HT7+ cells) (B, T and NK lymphocytes, monocytes, and polynuclear cells) in the different groups of individuals.
次要结局
- Relationship between Multiple sclerosis treatment on inflammation and serotonin production in serum(Day 15)
- Functional activity of the 5-HT7 receptor on PBMC: mRNA expression studies(Day 15)
- Functional activity of the 5-HT7 receptor on PBMC: protein studies(Day 15)
- Expression of the 5-HT7 receptor after positive selection of different cell populations from PBMC(Day 15)
- Expression of the different isoforms of the 5-HT7 receptor on PBMC(Day 15)