Healthy VolunteersBregNCT02615951
Characterization of Breg Cells
A study testing blood sampling in people with Healthy Volunteers and Arthritis, Rheumatoid, run by University Hospital, Montpellier at 1 site in France.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers, Arthritis, Rheumatoid
- What is being tested?
- blood sampling
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteFrance
- Study dates
- 2 Oct 2015to 10 Sep 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- RA responding to ACR/EULAR 2010 criteria
Who cannot join
- steroid> 10 mg/d
- previous use of biological disease-modifying antirheumatic drug (DMARD)
- age<18 years
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Characterization of B Regulatory (Breg) Cells in Healthy Subjects and in Rheumatoid Arthritis (RA)
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.
Read the detailed description
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:
- To identify genes and surface proteins differentially expressed between Breg and other B Lymphocytes (BL) in patients with RA.
- To identify nutrient transporters, chemokine receptors, genes and surface proteins differentially expressed between Breg and other BL in healthy subjects.
- To compare the expression of nutrient transporters, chemokine receptors, genes and surface proteins between Breg Breg controls and subjects with RA.
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:
- RA: patient meets the criteria ACR (American College of Rheumatology) -EULAR (European League Against Rheumatism) 2010, naïve and biotherapy with corticosteroids less than 10 mg / day, stable for at least a week.
- Controls: matched for age and sex to RA patients, with no systemic disease.
Endpoints
- Main: the average flow cytometry fluorescence intensity nutrient carriers and the percentage of BL expressing the different chemokine receptors
- Secondary: transcriptome analysis and proteomics surface with cytometric confirmation of protein expression of RNA and proteins identified.
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.
- Conditions
- Healthy Volunteers, Arthritis, Rheumatoid
- Being tested
- blood sampling
- Keywords
- Regulatory B cells (Breg), Genes, Cell surface proteins, Nutrient transporters, Chemokine receptors
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood samplingOther
Blood sample retrieval for biological and genetic analysis and comparison
| Study group | Role | What they receive |
|---|---|---|
| Nutrient transporters study | Other | Blood sampling from 10 patients vith RA and 10 control patient for biological analysis and measure of nutrient transporters expression Receives: Other: blood sampling |
| Chemokine receptors study | Other | Blood sampling from 10 patients vith RA and 10 control patient for biological analysis and measure of chemokine receptors expression Receives: Other: blood sampling |
| Genes study | Other | Blood sampling from 10 patients vith RA and 10 control patient for biological analysis and measure of genes expression Receives: Other: blood sampling |
| Protein surface study | Other | Blood sampling from 10 patients vith RA and 10 control patient for biological analysis and measure of protein surface expression Receives: Other: blood sampling |
| 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. Receives: Other: blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 :
- Medium fluorescence intensity of B lymphocytes for ASCT2, Glut1, PiT1, PiT2, RFT1\&3
- Percentage of B lymphocytes expressing chemokine receptors CCR4, CCR7, CCR9, CXCR3, CXCR4 and CXCR5
Measured: after analysis of the blood sample from the subject selected for the primary outcome mesure. Estimated at half a year after subject recruitement started
Secondary outcomes (4)
Identification of genes and surface receptors expressed differentially between Breg and others B cells in patients with RA
Measured: 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
Measured: 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
Measured: 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
Measured: Estimated at 6 month after end of subject recruitement
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2015 (estimated)
- Study start2 Oct 2015
- Primary completion10 Sep 2018
- Study completion10 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Montpellier
- Sponsor type
- University, hospital or other
- Collaborators
- Centre Hospitalier Universitaire de Nīmes, Institut de Génétique Moléculaire de Montpellier
- Responsible party
- Sponsor
- Investigators
- Claire I Daien, MD PhD, Principal investigator, Montpellier teaching hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02615951
- Sponsor's protocol ID
- 9461
- Acronym
- Breg
- Status last verified
- Jun 2026
- First submitted
- 28 May 2015
- Last updated
- 15 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 29774031
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of B Regulatory (Breg) Cells in Healthy Subjects and in Rheumatoid Arthritis (RA)
- ClinicalTrials.gov ID
- NCT02615951
- Acronym / sponsor ID
- Breg / 9461
- Conditions
- Healthy Volunteers, Arthritis, Rheumatoid
- Keywords
- Regulatory B cells (Breg), Genes, Cell surface proteins, Nutrient transporters, Chemokine receptors
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- University Hospital, MontpellierUniversity, hospital or other
- Collaborators
- Centre Hospitalier Universitaire de Nīmes, Institut de Génétique Moléculaire de Montpellier
- Study start
- 2 Oct 2015 (actual)
- Primary completion
- 10 Sep 2018 (actual)
- Study completion
- 10 Sep 2018 (actual)
- First posted
- 26 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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:
- To identify genes and surface proteins differentially expressed between Breg and other B Lymphocytes (BL) in patients with RA.
- To identify nutrient transporters, chemokine receptors, genes and surface proteins differentially expressed between Breg and other BL in healthy subjects.
- To compare the expression of nutrient transporters, chemokine receptors, genes and surface proteins between Breg Breg controls and subjects with RA.
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:
- RA: patient meets the criteria ACR (American College of Rheumatology) -EULAR (European League Against Rheumatism) 2010, naïve and biotherapy with corticosteroids less than 10 mg / day, stable for at least a week.
- Controls: matched for age and sex to RA patients, with no systemic disease.
Endpoints
- Main: the average flow cytometry fluorescence intensity nutrient carriers and the percentage of BL expressing the different chemokine receptors
- Secondary: transcriptome analysis and proteomics surface with cytometric confirmation of protein expression of RNA and proteins identified.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Nutrient transporters study | Other | Other: blood samplingBlood sampling from 10 patients vith RA and 10 control patient for biological analysis and measure of nutrient transporters expression |
| Chemokine receptors study | Other | Other: blood samplingBlood sampling from 10 patients vith RA and 10 control patient for biological analysis and measure of chemokine receptors expression |
| Genes study | Other | Other: blood samplingBlood sampling from 10 patients vith RA and 10 control patient for biological analysis and measure of genes expression |
| Protein surface study | Other | Other: blood samplingBlood 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 | Other: blood samplingBlood 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- RA responding to ACR/EULAR 2010 criteria
Key exclusion criteria (3 listed)
- steroid> 10 mg/d
- previous use of biological disease-modifying antirheumatic drug (DMARD)
- age<18 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood samplingBlood sample retrieval for biological and genetic analysis and comparison | Other | Chemokine receptors study, Genes study, Nutrient transporters study, Protein surface & genes data validation, Protein surface study |
Primary outcome
Identification of nutrient transporters' and of chemokine receptors' differentially expressed between Breg and other B cells in patients with RA
Time frame: after analysis of the blood sample from the subject selected for the primary outcome mesure. Estimated at half a year after subject recruitement started
Comparison between Breg (B IL-10+) and IL-10 non secreting B lymphocytes (B IL-10 -) in RA patient of : * Medium fluorescence intensity of B lymphocytes for ASCT2, Glut1, PiT1, PiT2, RFT1\&3 * Percentage of B lymphocytes expressing chemokine receptors CCR4, CCR7, CCR9, CXCR3, CXCR4 and CXCR5
4 secondary outcomes
Identification of genes and surface receptors expressed differentially between Breg and others B cells in patients with RA
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Estimated at 6 month after end of subject recruitement
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2026.
- Results publication: PubMed 29774031Mielle 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Claire I Daien, MD PhD principal investigator
Montpellier teaching hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing blood sampling in people with Healthy Volunteers and Arthritis, Rheumatoid, run by University Hospital, Montpellier at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of nutrient transporters' and of chemokine receptors' differentially expressed between Breg and other B cells in patients with RA (time frame: after analysis of the blood sample from the subject selected for the primary outcome mesure. Estimated at half a year after subject recruitement started). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02615951, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2026.