MUltiple Sclerosis : T Cell / B Cell Exploration (MUST-BE)
T Cell/B Cell Collaboration in Multiple Sclerosis: Exploring an Intimate Relationship
調査の概要
状態
条件
詳細な説明
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the Central Nervous System (CNS) affecting mostly young adults between 20 and 40 years of age. This disease is the leading cause of non-traumatic disability in young adults.
MS has long been considered a predominantly T-cell mediated disease. However, the remarkable efficacy of anti-CD20 monoclonal antibodies in this disease has demonstrated the major role of B-cell in the pathophysiology of this disease.
The B-cell have many functions: these cells are indeed able to secrete cytokines (pro and anti inflammatory), to present antigens to T lymphocytes, but also to differentiate into plasmocytic cells and thus to secrete immunoglobulins. Several studies have shown that B-cell in patients with MS secrete significantly more pro-inflammatory cytokines (GM-CSF, IL-6, TNFα). In addition, infiltrates and tertiary lymphoid structures have been found in the meninges of patients with MS, particularly in progressive forms of the disease. It seems clear to this day that these cells are strongly involved in the development of MS. Despite the many advances made recently in understanding the role of B-cell in the pathophysiology of MS, the precise involvement of plasma cells and their functions at different stages of the disease remains unclear.
Folluclar helper T cells (TFH) play a crucial role in lymphocyte B differentiation. These cells are located within the germinal centers in the secondary lymphoid organs, and their memory compartment also circulates in the blood. Several circulating TFH subpopulations have recently been defined, with different "helping" capacities.
This study, an ancillary to ABCD-SEP (NCT03744351), will be interested in more precisely characterizing circulating and infiltrating TH cells in Multiple Sclerosis whether at the transcriptomic level or at the functional level.
研究の種類
入学 (実際)
連絡先と場所
研究場所
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-
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Rennes、フランス、35033
- Rennes University Hospital
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
The population concerned is the same as the one participating in the ABCD-SEP study.
These patients gave their consent for the remaining biological samples to be used for ulterior research
説明
Inclusion Criteria:
Regarding MS patients (remitting or progressive untreated):
- Adult (age greater than or equal to 18 years) of both sexes;
- MS fulfilling the criteria of McDonald 2017;
- Remittent or progressive form;
- No immunomodulatory or immunosuppressive therapy for at least 3 months;
- Free, informed and written consent signed by the patient.
Regarding Clinically Isolated Syndrome:
- Adult (age greater than or equal to 18 years) of both sexes;
- Clinically isolated syndrome suggestive of MS (at least two typical lesions in two different locations);
- Patient receiving a Lumbar Puncture (PL) for diagnostic purposes;
- No immunomodulatory or immunosuppressive therapy for at least 3 months;
- Free, informed and written consent signed by the patient.
Regarding non-MS patients with neurological inflammatory disease:
- Adult (age greater than or equal to 18 years) of both sexes;
- Patient with non-MS neurological inflammatory disease (examples: meningitis, neurolupus, neurosarcoidosis...);
- Patients with PL for diagnostic or surveillance purposes;
- No immunomodulatory or immunosuppressive therapy for at least 3 months;
- Free, informed and written consent signed by the patient.
Regarding healthy volunteers:
- Adult (age greater than or equal to 18 years) of both sexes;
- Free, informed and written consent signed by the volunteer.
Exclusion Criteria:
Regarding all patients:
- Pregnancy;
- Breastfeeding;
- Treatment with corticotherapy in the last month;
- Patient not affiliated to health insurance;
- Persons major subject to legal protection (safeguard of justice, guardianship, tutorship), persons deprived of their liberty.
Regarding healthy volunteers:
- Pregnancy;
- Breastfeeding;
- Not affiliated to social security;
- Persons major subject to legal protection (safeguard of justice, guardianship, tutorship), persons deprived of their liberty.
研究計画
研究はどのように設計されていますか?
デザインの詳細
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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To compare the transcriptome profile of infiltrating TFH cells from CIS patients to non-MS patients with neurological inflammatory diseases
時間枠:At inclusion
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Comparison of each gene expression of infiltrating TFH cells from CIS patients to those of non-MS patients with neurological inflammatory diseases by RNAsequencing
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At inclusion
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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To compare the transcriptome profile of infiltrating TFH cells from CIS patients to healthy volunteers.
時間枠:At inclusion
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Comparison of each gene expression of infiltrating TFH cells from CIS patients to those of healthy volunteers (HV) by RNAsequencing
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At inclusion
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To compare the B cell differentiation helping abilities of TFH cells from MS patients to those of HV
時間枠:At inclusion
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Analysis of B cell phenotype after 7 days of in vitro coculture assays and comparison of the frequencies between MS patients and HV
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At inclusion
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To compare the migration abilities of TFH cells from MS patients to those of HV
時間枠:At inclusion
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Analysis of the rate, number and phenotype of migrating TFH cells after 12 to 24 hours using an in vitro model of Blood Brain Barrier in MS patients compared to HV
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At inclusion
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協力者と研究者
捜査官
- 主任研究者:Laure Michel、Rennes University Hospital
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 35RC19_8871_MUST-BE
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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