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| Name | Class |
|---|---|
| Centre Hospitalier Universitaire de Nīmes | OTHER |
| Institut de Génétique Moléculaire de Montpellier | OTHER |
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Recently, it has been shown that B cells could also have regulatory functions through the secretion of interleukin 10 (IL-10). They are called the B regulatory cells (Breg). In the mouse model the most commonly used of rheumatoid arthritis, collagen-induced arthritis (CIA), the transfer Breg helps prevent the development of CIA and cure established arthritis. The investigators have recently shown that Breg were decreased in patients with RA compared to controls and that the rate of Breg was inversely correlated with disease activity and autoantibody. These results thus suggest that the lack of IL-10 secretion by B cells plays an important role in the pathophysiology of RA. Nevertheless, in humans, the Breg remain poorly understood. The main objective of this project is to better characterize the B capable of producing IL-10 both in subjects with RA and controls. Understanding which induces the secretion of IL-10 by B could allow to consider new therapeutic approaches in autoimmune diseases, including in RA.
The investigators therefore aim to identify nutrient transporters, chemokine receptors, genes and surface proteins differentially expressed between Breg and other B cells in patients with RA and in controls.
Rational: Rheumatoid arthritis (RA), the most common inflammatory joint disease, is often associated with irreversible joint destruction and can involve the prognosis of patients. If treatments to stabilize the disease are now available, research continues to try to permanently cure the disease. It is well established that the B cells have a pathogenic role in RA. More recently, it has been shown that B cells could also have regulatory functions through the secretion of interleukin 10 (IL-10). They are called the B regulatory cells (Breg). In the mouse model the most commonly used of rheumatoid arthritis, collagen-induced arthritis (CIA), the transfer Breg helps prevent the development of CIA and cure established arthritis. The investigators have recently shown that Breg were decreased in patients with RA compared to controls and that the rate of Breg was inversely correlated with disease activity and autoantibody levels. These results thus suggest that the lack of IL-10 secretion by B cells plays an important role in the pathophysiology of RA. Nevertheless, in humans, the Breg remain poorly understood. The project's main objective is to better characterize the B capable of producing IL-10 both in subjects with RA and controls. Understanding which induces the secretion of IL-10 by B could allow to consider new therapeutic approaches in autoimmune diseases, including in RA.
Objectives:
Principal: To identify nutrient transporters and chemokine receptors differentially expressed between Breg and other B cells in patients with RA.
Secondary:
Methods:
Design: Cross-sectional study involving bicentric rheumatology services in Montpellier and Nîmes to recruitment; our research team at the Translational IGMM Nîmes and immunology laboratory for biological analyzes.
Population:
Endpoints
Number of subjects: 50 controls and 50 RA patients (10 each for each of the 3 methods of comparison Breg / B IL10- and 10 each for each of the two stages of validation). Each patient will have a visit. The expected study duration is 2 years.
Statistical analysis: Comparing ratios B + IL-10 / IL-10-B between RA patients and controls by Student or Mann-Whitney tests.
Expected Results and Prospects: This project will allow us to better define and understand the Breg in patients with RA and in controls. If the investigators can find specific extracellular markers for Breg, this will simplify the further study of these cells. Understanding allowing BL becoming regulator and this explains the lack of IL-10 by the BL in RA could open new therapeutic perspectives.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nutrient transporters study | Other | Blood sampling from 10 patients vith RA and 10 control patient for biological analysis and measure of nutrient transporters expression |
|
| Chemokine receptors study | Other | Blood sampling from 10 patients vith RA and 10 control patient for biological analysis and measure of chemokine receptors expression |
|
| Genes study | Other | Blood sampling from 10 patients vith RA and 10 control patient for biological analysis and measure of genes expression |
|
| Protein surface study | Other | Blood sampling from 10 patients vith RA and 10 control patient for biological analysis and measure of protein surface expression |
|
| Protein surface & genes data validation | Other | Blood sampling from 10 patients vith RA and 10 control patient for biological analysis and measure for validation of the data from "protein surface study" and "genes study" arms analysis. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| blood sampling | Other | Blood sample retrieval for biological and genetic analysis and comparison |
|
| Measure | Description | Time Frame |
|---|---|---|
| Identification of nutrient transporters' and of chemokine receptors' differentially expressed between Breg and other B cells in patients with RA | Comparison between Breg (B IL-10+) and IL-10 non secreting B lymphocytes (B IL-10 -) in RA patient of :
| after analysis of the blood sample from the subject selected for the primary outcome mesure. Estimated at half a year after subject recruitement started |
| Measure | Description | Time Frame |
|---|---|---|
| Identification of genes and surface receptors expressed differentially between Breg and others B cells in patients with RA | Estimated at 6 month after end of subject recruitement | |
| Identification of nutrient transporters and chemokine receptors expressed differentially between Breg and others B cells in control patients |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Claire I Daien, MD PhD | Montpellier teaching hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Regional University Hospital | Montpellier | Hérault | 34295 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29774031 | Result | Mielle J, Audo R, Hahne M, Macia L, Combe B, Morel J, Daien C. IL-10 Producing B Cells Ability to Induce Regulatory T Cells Is Maintained in Rheumatoid Arthritis. Front Immunol. 2018 May 3;9:961. doi: 10.3389/fimmu.2018.00961. eCollection 2018. |
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| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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| Estimated at 6 month after end of subject recruitement |
| : Identification of genes and surface receptors expressed differentially between Breg and others B cells in control patients | Estimated at 6 month after end of subject recruitement |
| Comparison of nutrient transporters, chemokine receptors, gene and protein surface expression expressed between Breg in patients with RA and Breg in control patients | Estimated at 6 month after end of subject recruitement |
| D003240 |
| Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |