ESR 17Immune monitoring of macrophages in the development and progression of rheumatoid arthritis and immune checkpoint inhibitor-induced rheumatic manifestations - POSITION FILLED

PhD research

Host:

Dr Conny J. van de Laken

Department of Rheumatology

Amsterdam UMC, location VUMC

Duration: 48 months

Background

In rheumatoid arthritis (RA), synovial macrophage infiltration is hallmark of the disease, reflecting disease activity in early and established stages. Moreover, reduction of synovial macrophage infiltration serves as a sensitive biomarker for therapy response monitoring. To this end, macrophage imaging has been explored as a non-invasive diagnostic tool for imaging of early RA disease activity as well as monitoring response to therapeutics. Recently, we successfully demonstrated the feasibility of positron emission tomography (PET) for macrophage imaging of two target proteins (folate receptor β (FRβ) and translocator protein (TSPO)) in arthritic rats and RA patients.

Beyond classical arthritis development, there is emerging evidence that 5-20% of cancer patients treated with immune checkpoint inhibitors (anti-PD-1/PD-L1) develop variable immune-related adverse events (irAEs) with clinical manifestations of inflammatory arthritis which may not only involve aberrancies in T cell function, but also in macrophage polarization. Hence, immune monitoring of monocyte-macrophages in classical RA vs irAE-induced arthritis may provide new insights in the role of macrophages in RA pathogenesis in autoimmune diseases and optimal application of macrophage PET imaging for disease and therapy response monitoring.

Approach 

The project will cover two parts: (a) monocyte-macrophage immune-monitoring, using flow cytometry and immunohistochemistry examination of monocyte /macrophage (polarization) markers in peripheral blood, synovial fluid and/or synovial tissue material of early and established RA patients and peripheral blood of cancer patients with irAEs, and (b) based on these results , PET imaging feasibility studies in arthritic rats will be performed for a selected novel macrophage tracer, a radiolabeled PD-1 or PD-L1 PET tracer, and [18F]fluoro-PEG folate as a reference tracer.

Our research team

  • - Dept. of Rheumatology (location VUmc & AMC): Dr. C.J. vd Laken (associate professor and expert in translational molecular imaging of immunology), dr. G. Jansen (biochemist and expert in areas of therapeutics and drug resistance), prof. dr. R.F. v Vollenhoven (head of department and expert in large clinical trials in several reumatic diseases, such as rheumatoid arthritis and SLE).

    - Dept. of Medical Oncology (Cancer Center Amsterdam): Prof. dr. T.D. de Gruijl, dr. M. Labots (experts in immunological processes in oncology).

    - Dept. Radiology & Nuclear Medicine (AMC-location VUmc): dr. W. Beaino, dr. D. Vugts, prof. dr. A.D. Windhorst, prof. dr. G.A.M.S. van Dongen (expert team to perform translational molecular imaging studies in immunology).

    - Dept. of Molecular Cell Biology and Immunology (Amsterdam Immunology & Infection Institute): dr. J.J. Garcia Vallejo (expert in experimental immunology).

Website: https://ams-rc.com/