PMR Research On Disease Mechanisms In Synovium (PROMIS)
Concept
The ‘PMR Research on Disease Mechanisms In Synovium’ (PROMIS) project is dedicated to unravelling the pathobiology of PMR. Ultrasound-guided synovial biopsies will be obtained from the subacromial-subdeltoid bursa of patients with PMR. A combination of immunohistochemistry and single-cell RNA sequencing will be applied to gain unprecedented insight into the synovial pathobiology of PMR.
Facts and Figures
K Van der Geest
University Medical Center Groningen
k.s.m.van.der.geest@umcg.nl
Meet the Team
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University Medical Center Groningen
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University Medical Center Groningen
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UMC Groningen
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ZGT Hospital
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ZGT Hospital
Objectives
The overarching aim of the PROMIS project is to identify synovial targets for treatment in PMR.
- To identify immunological targets for already existing therapies in PMR synovium.
- To identify senescent cells in PMR synovium as potential targets for treatment.
- To determine cellular heterogeneity and networks in PMR synovium on a molecular level.
Goals/Milestones
- Start of the project March 2021
- Collection of biopsies from 15 patients at mid-term report and 30 patients at final report.
- Results on Study Aim 1 and Study Aim 2 available for 10 patients at the mid-term report.
- Final results on Study Aim 1, Study Aim 2 and Study Aim 3 available at the final report.
- Publication of results in the top 5 peer-reviewed journals in the field of rheumatology.
- Interim report to patients’ organisation (Vasculitis Stichting).
- Dissemination of results via conferences (EULAR, International GCA/PMR Workshops)
Publications
- Jiemy WF, Zhang A, Boots AMH, Heeringa P, Sandovici M, Diepstra A, Hein S, Dasgupta B, Brouwer E, van der Geest KS. Expression of interleukin-6 in synovial tissue of patients with polymyalgia rheumatica. Ann Rheum Dis. 2023 Mar;82(3):440-442. doi: 10.1136/ard-2022-222873. Epub 2022 Aug 12. PMID: 35961758.
- Reitsema RD, Jiemy WF, Wekema L, Boots AMH, Heeringa P, Huitema MG, Abdulahad WH, van Sleen Y, Sandovici M, Roozendaal C, Diepstra A, Kwee T, Dasgupta B, Brouwer E, van der Geest KSM. Contribution of pathogenic T helper 1 and 17 cells to bursitis and tenosynovitis in polymyalgia rheumatica. Front Immunol. 2022 Aug 11;13:943574. doi: 10.3389/fimmu.2022.943574. PMID: 36032100; PMCID: PMC9402989.
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van der Geest KSM, Sandovici M, Nienhuis PH, Slart RHJA, Heeringa P, Brouwer E, Jiemy WF. Novel PET Imaging of Inflammatory Targets and Cells for the Diagnosis and Monitoring of Giant Cell Arteritis and Polymyalgia Rheumatica. Front Med (Lausanne). 2022 Jun 6;9:902155. doi: 10.3389/fmed.2022.902155. PMID: 35733858; PMCID: PMC9207253
Meeting presentations:
- Dutch Society for Rheumatology Annual Meeting, 2021. Characterization of synovial fluid T cell in Polymyalgia Rheumatica: implication of Th1 and Tc1 responses. Oral presentation.
- ACR Convergence, 2021. Characterization of synovial fluid T cell in Polymyalgia Rheumatica: implication of Th1 and Tc1 effector memory profiles. Poster presentation, Abstract no. 1407.
- EULAR Annual Congress, 2022. Proinflammatory monocytes and macrophages in synovial fluid and bursal tissue of patients with polymyalgia rheumatica: potent producers of IL-6 and GM-CSF. Oral presentation, Abstract no. 4396.
- Dutch Society for Rheumatology Annual Meeting, 2022. Proinflammatory monocytes and macrophages in synovial fluid and bursal tissue of patients with polymyalgia rheumatica: potent producers of IL-6 and GM-CSF. Poster presentation.
Patient Voice
Half of patients with PMR are currently ‘sentenced’ to prolonged use of glucocorticoids and frequently develop complications caused by this treatment. This project will accelerate the introduction of existing, targeted therapies (i.e. already used for other diseases) for patients with PMR by providing a clear rationale for such therapies. The ultimate goal of the study is to make long-term glucocorticoid therapy obsolete and to improve the patients’ well-being.