JAK-i on RA B-lymphocytes Tolerance and Disease Resolution Through JAK Signaling In Rheumatoid Arthritis
Dissecting the Role of B Lymphocytes in the Loss of Immunological Tolerance and Disease Resolution Through JAK Signaling In Rheumatoid Arthritis
1 other identifier
observational
50
1 country
1
Brief Summary
The study will reveal the transcriptomic signature linked to the aberrant activation of B lymphocytes in RA identifying novel molecular potential targets for inflammation resolution and immune tolerance promotion. The combination with B lymphocytes phenotyping will dissect the impact of the identified genes on B lymphocyte maturation and activation in RA. Moreover, in vitro study on B lymphocyte cultures using selective JAK1 inhibition will reveal, at deeper level, its transcriptomic effect on RA B lymphocytes activation profile and phenotype, providing the discovery of new biomarkers of the loss of immunological tolerance, active disease and long lasting disease remission.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for all trials
Started Jul 2021
Typical duration for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 29, 2021
CompletedFirst Submitted
Initial submission to the registry
February 22, 2023
CompletedFirst Posted
Study publicly available on registry
March 3, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 2, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2023
CompletedMarch 3, 2023
February 1, 2023
1.8 years
February 22, 2023
February 22, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Peripheral blood and synovial tissue B lymphocyte atlas
24 months
Study Arms (5)
ACPA/RFpos asyntomatic individuals
ACPA and/or RF positive individuals without active arthritis
Naive Active RA
Treatment-naive active RA (disease duration\<1 year)
Resistant RA
Active despite treatment RA
Remission RA
RA in sustained clinical and ultrasound remission
Control Group
Individuals asymptomatic for joint inflammation without ACPA/RF positivity
Interventions
All individuals will undergo peripheral venous blood sampling and ultrasound-guided synovial tissue biopsy following a standardized procedure. B-lymphocytes will be sorted from PBMCs isolated by Ficoll gradient method using magnetic CD19-microbeads whereas tissue B-lymphocytes will be isolated from synovial tissue biopsies digested with Liberase. CD19 positive cells from PBMC will be incubated with pro-inflammatory molecules in presence or absence of Ubadacitinib. After stimulation, CD19 positive cells will be collected and processed for single cell RNA sequencing. Moreover, the impact of JAK-1 selective inhibition on B-lymphocyte cultures stimulation will be tested using ELISA method for the assessment of cytokines/chemokines production. Synovial tissue and synovial tissue B-lymphocyte subpopulations will be assessed through FACS analysis using IgD/CD27 classification. Finally, we will compare the transcriptomic profile of synovial tissue B lymphocytes from 5 subject groups.
Eligibility Criteria
This is an interventional research without experimental drug which will be performed at the Division of Clinical Immunology of the Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome, Italy, where patients with Rheumatoid Arthritis will undergo to synovial tissue inflammation assessment through minimally invasive US-guided synovial tissue biopsy.
You may qualify if:
- Signed Written Informed Consent. Before any study procedures are performed,subjects will have the details of the study described to them, and they will be given a written informed consent document to read. Then, if subjects consent to participate in the study, they will indicate that consent by signing and dating the informed consent document in the presence of trained study personnel.
- Patients fulfilling classification criteria for Rheumatoid Arthritis (2010 ACR/EULARclassification criteria)
- Age: 18-70 years
- For preclinical cohort: Individuals with positivity for ACPA or IgM/IgA RF without clinical signs of arthritis, whose positivity is not related to other concomitant pathologic conditions.
- For naive to treatment cohort: RA patients without previous exposure to conventional DMARDs or biologic/targeted synthetic-DMARDs.
- For resistant to treatment cohort: RA patients with failure to previous conventionalDMARDs for inadequate response or side effects.
- For remission RA cohort: RA patients in sustained clinical and ultrasound remission as stated in section 3.3.1.
- For healthy control cohort: Healthy donors will be aged from 18 to 70 years.
You may not qualify if:
- Severe and uncontrolled infections such as sepsis and opportunistic infections.
- Patients who are currently included in any interventional clinical trial in RA.
- RA patients in therapy with other biologics.
- Healthy donors receiving anti-inflammatory drugs
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Division of Clinical Immunology, Fondazione Policlinico Universitario A. Gemelli-IRCCS
Rome, 00168, Italy
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- CASE CONTROL
- Time Perspective
- CROSS SECTIONAL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Prof.
Study Record Dates
First Submitted
February 22, 2023
First Posted
March 3, 2023
Study Start
July 29, 2021
Primary Completion
May 2, 2023
Study Completion
December 31, 2023
Last Updated
March 3, 2023
Record last verified: 2023-02