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

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/

Your profile

        • - Master’s degree in Biomedical Sciences with affinity for immunology and translational research

          - Rheumatology and Nuclear Medicine interest

          - Relevant skills in immunological methods

          - Preferably advanced skills of working with animals

          - Flexible, pro-active team spirit, but also to work independently

          - Proficiency in English language (written & verbal).

Our offer

All ARCAID ESRs receive a full employment contract for 4 years, according to the Collective Employment Agreement (CAO) of the Dutch University Medical Centres. The monthly salary based on a 36-hour work starts from €2.422,- with yearly increments to a maximum of € 3.103,-. This 4-year PhD position is funded by the  Marie Skłodowska-Curie actions of the European Union's Horizon 2020 COFUND program under grant agreement No 847551. There is no separate budget available for mobility as it is already included in the ESR salary. ESRs may attend external courses, conferences or workshops. If applicable or required, additional expenses for training and conference participation and the travel to a Partner Organisation will be covered by the project. The ESR salary meets the requirements of the Dutch Immigration Department to allow family members to move to the Netherlands. It is at the convenience of the ESR to decide on this family movement since the Amsterdam UMC will not cover additional expenses regarding mobility of spouse nor for the required accompanying residence permits. In addition to their individual scientific projects, all fellows will have the opportunity to attend international progress meetings, scientific conferences and summer schools. Additionally, they benefit from further continuing education, which includes internships and secondments, a variety of training modules as well as transferable skills courses. See recruitment procedure.

Your application

See recruitment procedure. You can apply using the online application form. For more information about the project you can contact Dr. Conny van der Laken.