Effect of the Inhibitors of the Way JAK-STAT on Regulatory B Cells

Study Overview
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Brief Summary
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This study will investigate whether inhibitors of the JAK / STAT signaling pathway can increase anti-inflammatory functions of B cells in patients with RA using in vitro and in vivo experiments.

Detailed Description
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This study will first analyze the effect of inhibitors of the JAK / STAT pathway in vitro on B-cell phenotypes and functions in 30 RA patients and 30 patients with osteoarthritis. It will also study the phenotypes and functions of B cells in RA patients for whom JAK / STAT inhibitor treatment has been prescribed by the patient's usual rheumatologist. The analysis will be done before the start of treatment and 3 months later. The phenotypes of B-cells will be assessed by flow cytometry with intra- and extra-cellular stainings. The functions of B cells will be assessed by their ability to differenciate naïve T cells in coculture.

Official Title
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Effect of the Inhibitors of the Way JAK-STAT on Regulatory B Cells in the Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Other: Blood sample analysis of patients treated as standard care


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: General criteria Patient, of 18 and more years old Subject affiliated to a social security system Subject not being in period of exclusion with regard to another protocol Absence of pregnancy in the inclusion (date of the last period, use of a contraceptive method, ß -HCG impulsive person in case of doubt) Informed consent Criteria of inclusion of the group rheumatoid arthritis (in vitro studies): Rheumatoid arthritis, corresponding to the the classification ACR / EULAR 2010 criteria Criteria of inclusion of the group arthritis (in vitro studies): Spinal degenerative osteoarthritis or degenerative osteoarthritis of the members, according to the clinical and radiological elements. Criteria of inclusion of the group rheumatoid arthritis, longitudinal study at the patients treated by JAK / STAT inhibitors : Rheumatoid Polyarthritis, corresponding to the classification ACR / EULAR 2010 criteria Patient to whom a treatment by inhibitor of the way JAK / STAT was proposed in current care of rheumatoid arthritis. Exclusion criteria: General criteria Corticosteroid therapy superior to 10 mg / j Drip of corticoids in the previous month Pregnant or breast-feeding Patients Patient under protection(saving) of justice Under guardianship Patient or guardianship Current Infection Criteria of non-inclusion of the group rheumatoid polyarthritis ( in vitro studies): Treatment by immunomodulateur or biotherapics (anti-TNF alpha, tocilizumab, abatacept or rituximab) in the previous year Criteria of non-inclusion of the group arthritis ( in vitro studies): History of autoimmune disease or néoplasie Treatment by immunomodulateur or biotherapics (anti-TNF alpha, tocilizumab, abatacept or rituximab) Criteria of non-inclusion of the group rheumatoid arthritis, longitudinal study at the patients treated by JAK / STAT inhibitors : Treatment by rituximab in the previous year

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Rheumatoid arthritis<br>Patients responding to ACR/EULAR 2010 criteria and Blood sample analysis of patients treated as standard care | Other: Blood sample analysis of patients treated as standard care<br>* Blood sample to analyse percentage of blood cells (regulatory B cells et T cells)<br>|
| Other: Osteoarthritis<br>Control patients and Blood sample analysis of patients treated as standard care | Other: Blood sample analysis of patients treated as standard care<br>* Blood sample to analyse percentage of blood cells (regulatory B cells et T cells)<br>|
| Other: Rheumatoid arthritis with JAK/STAT inhibitors<br>Standard use of JAK/STAT inhibitors and Blood sample analysis of patients treated as standard care | Other: Blood sample analysis of patients treated as standard care<br>* Blood sample to analyse percentage of blood cells (regulatory B cells et T cells)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of regulatory B cells induced by JAKi in vitro | IL-10+ CD19+ cells after in vitro exposure of JAKi | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of regulatory T cells induced by JAKi treated B cells in vitro | CD25hiCD126lo/-CD4+ after 3 days of coculture with JAKi pretreated B cells | 4 months | 
| Percentage of Th1 induced by JAKi treated B cells in vitro | Interferon gamma+CD4+ after 3 days of coculture with JAKi pretreated B cells | 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid arthritis, Regulatory B cells, JAK/STAT inhibitors