Immunopathology of Polymyalgia Rheumatica on Shoulder Bursae's Biopsies

Polymyalgia Rheumatica Clinical Trial

— BAOBAB  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04727879
• Other study ID #: 29BRC20.0158
• Status: Completed
• Phase: N/A
• Start date: April 7, 2021
• Est. completion date: August 13, 2022

Study information

• Verified date: July 2023
• Source: University Hospital, Brest
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 13, 2022
• Est. primary completion date: July 13, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Giant Cell Arteritis
• Polymyalgia Rheumatica

Intervention

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.
• 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.
• Blood sample
A blood sample taken during routine care and unused will also be collected from patients and controls for immunoassays.

Locations

Country	Name	City	State
France	CHU de Brest - Service de rhumatologie	Brest

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Brest

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Cytokinic (other than IL-6) infiltration of tissues		Day 0
Secondary	Serum cytokine levels		Day 0
Secondary	Cytokine levels in joint or synovial fluid		Day 0
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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