Immunopathology of Polymyalgia Rheumatica on Shoulder Bursae's Biopsies (BAOBAB)

Beyond Analysis Of Blood Sample, to Approach Immunopathology of Polymyalgia Rheumatica on Shoulder Bursae's Biopsies: the BAOBAB Study

The work carried out at the Brest University Hospital on serum immunological changes in patients with polymyalgia rheumatica (PMR) (based on clinical protocols TENOR, SEMAPHORE, THEN) made it possible to describe the changes in the distribution of lymphocyte subpopulations and cytokine levels during PPR, before and then under treatment compared to controls.

However, in systemic autoimmune or inflammatory pathologies, serum immunological mechanisms are rarely a reflection of intra-tissue mechanisms.

In the specific case of PMR, there are few data concerning muscular or joint immunological modifications. The investigators now wish to study the immunological modifications occurring at the tissue sites of interest, in particular in the shoulder bursae

Study Overview

• Status: Completed
• Conditions: Polymyalgia Rheumatica
• Intervention / Treatment: Procedure: Synovial membrane biopsy with puncture of synovial fluid; Procedure: Joint fluid sampling; Procedure: Blood sample

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Brest, France, 29200
    • CHU de Brest - Service de rhumatologie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

For everyone :

• Signed consent
• Patients over 50

Inclusion criteria :

For case patients:

• Addressed for PMR (diagnosis OR relapse)
• Score greater than or equal to 4 (without ultrasound criteria) or greater than or equal to 6 (with ultrasound criteria), according to the ACR / EULAR 2012 criteria for polymyalgia rheumatica, and suffering from bilateral scapular pain as well as an increased CRP level .
• Thickening of more than 2mm at least one shoulder bursae in ultrasound
• DAS-PPR> = 10

For witnesses:

- Shoulder surgery scheduled for mechanical pathology

Exclusion criteria :

For everyone :

• MRI with Gadolinium injection in the previous month- Clinical or paraclinical signs of giant cell arteritis
• Patient under protective measure or unable to consent
• Active cancer
• Active infection

For the cases:

- History of biotherapy treatment

For witnesses:

• History of inflammatory rheumatism
• Active inflammatory rheumatism

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: PMR; Patients with PMR will be offered biopsy of the synovial membrane with puncture of synovial fluid during cortisone infiltration for analgesic purposes. In case of associated peripheric arthritis, the patient will also be offered a joint fluid sample during a cortisonic infiltration for analgesic purposes, performed as part of routine care The study-specific examination that is not part of current practice is the synovial biopsy performed during the cortisonic infiltration procedure.	Procedure: Synovial membrane biopsy with puncture of synovial fluid; The biopsy of the shoulder bursae will be carried out thanks to a device Tru-cut (Tru-Cut Biopsy Needle), minimally invasive, introduced, as during an infiltration, within the bursa serosa.; Procedure: Joint fluid sampling; In case of associated peripheric arthritis, the patient will also be offered a sample of joint fluid during a cortisonic infiltration for analgesic purposes, performed as part of routine care.; Procedure: Blood sample; A blood sample taken during routine care and unused will also be collected from patients and controls for immunoassays.
Other: Control; Witnesses recruited into the orthopedic surgery department will be offered a synovial membrane biopsy during a shoulder surgery in the context of mechanical pathology.	Procedure: Synovial membrane biopsy with puncture of synovial fluid; The biopsy of the shoulder bursae will be carried out thanks to a device Tru-cut (Tru-Cut Biopsy Needle), minimally invasive, introduced, as during an infiltration, within the bursa serosa.; Procedure: Blood sample; A blood sample taken during routine care and unused will also be collected from patients and controls for immunoassays.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IL-6 marking	The main evaluation criterion is the intensity of the tissue IL-6 marking on the subacromio-deltoid bursa sections using the Hyperion technique.	Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cytokinic (other than IL-6) infiltration of tissues		Day 0
Serum cytokine levels		Day 0
Cytokine levels in joint or synovial fluid		Day 0
Tissue distribution of lymphocyte subpopulations by using the Hyperion mass cytometer (analysis of the intensity of the markings)	Fragments of the synovial membrane taken from patients and controls will be sent to the pathology laboratory. They will be fixed and slides covering the inflammatory region of interest will be prepared. These slides will be marked with antibodies directed against: - CD20, CD27, CD38, CD24, CD21, CD95, CD23, IgM, Tbet for B lymphocytes; - CD3, CD4, CD8, CD25, CD45RA, CD62L, CD28, FoxP3, CCR7, CD45RO and Bcl-2 for T lymphocytes; - CD14, CD11b and CD11c for monocytes; - CD66b for granulocytes and coupled to heavy metals and analyzed by the Hyperion mass cytometer. The intensity of the markings will be analyzed using the usual Hyperion analysis techniques.	Day 0
Serum distribution of lymphocyte subpopulations by using the HELIOS mass cytometer (analysis of the intensity of the markings)	Whole blood will be centrifuged and serum will be collected. Antibodies directed against: - CD20, CD27, CD38, CD24, CD21, CD95, CD23, IgM, Tbet for B lymphocytes; - CD3, CD4, CD8, CD25, CD45RA, CD62L, CD28, FoxP3, CCR7, CD45RO and Bcl-2 for T lymphocytes; - CD14, CD11b and CD11c for monocytes; - CD66b for granulocytes, aand Hnd coupled with heavy metals will be added to it before analysis by the HELIOS mass cytometer. The intensity of the markings will be analyzed using the usual HELIOS analysis techniques.	Day 0
Analysis of immunosenescence markers in tissues by HYPERION technology	Analysis of membrane markers related to immunosenescence in percent of cells expressing the marker and in MFI (Mean fluorescence intensity) by hyperion technology.	Day 0
Analysis of target molecules of treatments under study in PPR by ELISA technique	The target molecules of treatments under study in PPR (CTLA-4 for abatacept, janus kinases 1 and 2 for baricitinib) will be analyzed by ELISA techniques (concentration).	Day 0
Analysis of target molecules of treatments under study in PPR by proteomic techniques	The target molecules of treatments under study in PPR (CTLA-4 for abatacept, janus kinases 1 and 2 for baricitinib) will be analyzed by protéomic techniques (cytometry, % of cells expressing the marker, MFI)	Day 0
Complications of subacromio-deltoid purse in the 72h after biopsies : M1 phone call	The expected complications related to the synovial biopsy are: Pain at the biopsy site, Hematoma at the biopsy site, Functional impotence of the shoulder, on the biopsy side, greater than 72h, Hypoesthesia, dysesthesia at the biopsy site, Skin rash within 72h following the infiltration, Hypertensive surge documented within 72 hours of the infiltration, In case of pre-existing diabetes, diabetes imbalance within 72 hours of the infiltration.	Month 1

Collaborators and Investigators

• Sponsor: University Hospital, Brest

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2021
• Primary Completion (Actual): July 13, 2022
• Study Completion (Actual): August 13, 2022

Study Registration Dates

• First Submitted: January 7, 2021
• First Submitted That Met QC Criteria: January 26, 2021
• First Posted (Actual): January 27, 2021

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 28, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Skin Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Muscular Diseases; Vasculitis; Skin Diseases, Vascular; Vasculitis, Central Nervous System; Arteritis; Polymyalgia Rheumatica; Giant Cell Arteritis
• Other Study ID Numbers: 29BRC20.0158

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All collected data that underlie results in a publication
• IPD Sharing Time Frame: Data will be available beginning three years and ending fifteen years following the final study report completion
• IPD Sharing Access Criteria: Data access requests will be reviewed by the internal committee of Brest UH. Requestors will be required to sign and complete a data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No