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Autoimmune vasculitis: translational, immunological and imaging studies in patients with giant cell arteritis.

FDG-PET image of a vasculitis patient with uptake (in black) showing inflamed arteries.

Nature of the research:

At the Vasculitis Expertise Center of the UMCG, we perform translational and clinical research with the overall aim to improve the care of patients with vasculitis.

 

We offer various types of projects, which can be tailored to your interests.

  • Translational research: this involves immunological studies on arterial tissue and blood samples of patients with giant cell arteritis. The immunological findings will be linked to clinical characteristics and outcomes in the patients with giant cell arteritis.
  • Imaging research: this involves collection of clinical and imaging data. The diagnostic and prognostic value of existing and new imaging techniques will be evaluated.
  • Clinical research: Analyses of long-term follow-up data on patient-reported outcomes and effect of treatment; and development of questionnaires together with patients and healthy elderly study participants.

 

To learn more about vasculitis and our research, make sure to visit our website at www.vasculitiscentrum.nl.

 

If you would like to continue with research in our group upon completion of your project, it is possible to apply for a MD/PhD position.

Background / introduction:

Vasculitis is the name of a group of diseases in which the blood vessel wall becomes inflamed. Blood vessel inflammation can lead to blood flow obstruction, and organ/tissue damage. Giant cell arteritis (GCA) is the most common form of autoimmune vasculitis. It is a strictly aging-associated disease, since it only occurs after the age of 50. Involvement of cranial arteries may cause ischaemic complications such as irreversible blindness and stroke. Inflammation of large systemic arteries can result into formation of aortic aneurysms.

A timely diagnosis is important, since ischaemic complications may already develop early in the disease. An accurate diagnosis is also important to limit unnecessary exposure of patients to treatment. Since the 1950s, glucocorticoid therapy has remained the cornerstone of treatment for patients with giant cell arteritis. Unfortunately, many  patients suffer from (substantial) side effects of this treatment. Currently, there is a need for better diagnostic tools and more targeted therapies for giant cell arteritis.

 

Research question / problem definition:

We address the following unmet needs for giant cell arteritis:

  1. Better understanding of the immune pathology in the arterial wall. This will help to identify new targets of treatment for patients with giant cell arteritis. We hope to minimize the glucocorticoid use for giant cell arteritis in the future.
  2. Better understanding of the immune pathology in the blood. This will help to identify new diagnostic and prognostic biomarkers that can be measured in the blood of patients with (suspected) giant cell arteritis.
  3. Improve the diagnostic work-up with imaging techniques. We investigate and expand the use of already existing imaging techniques (ultrasonography, FDG-PET/CT) for giant cell arteritis. Furthermore, we explore new imaging techniques to better visualize vascular inflammation (PET tracers that target specific immune cells). We hope that invasive investigations (such as temporal artery biopsy) will not be needed anymore in the future.
  4. Patient-reported outcomes. Research into the impact of vasculitis and it’s treatment in order to improve the well-being of patients with vasculitis.

 

Visit our website to find specific information on our current research projects: https://www.vasculitiscentrum.nl/onderzoek-onderwijs/onderwijs

 

Workplan:

Interested students may work on one of the following project, or perhaps on the interface of two projects.

  1. Immune pathology in the arterial wall. Temporal artery biopsies and aortic tissue are evaluated by immunohistochemistry and transcriptome analysis.
  2. Immune pathology in the blood. Whole blood and serum/plasma samples are evaluated by flow cytometry, ELISA, Luminex and transcriptome analysis.
  3. Clinical and imaging data are collected and analysed. The diagnostic and prognostic value of the imaging techniques are evaluated. Furthermore, imaging findings will be linked to inflammation markers in the blood and disease activity during treatment. This will help clinicians to better understand the diagnostic value (and pitfalls) of these techniques.
  4. Patient-reported outcomes. Clinical and questionnaire data are collected and analysed. The effect of the treatment on the patients’ well-being is evaluated. Furthermore, the relationship between patient-reported outcomes and improvement of imaging / lab tests will be evaluated.

During your project, you will be supervised by a PhD student and you are invited to attend our weekly vasculitis meetings.

 

References:

Research at the Department of Rheumatology and Clinical Immunology / Vasculitis Expertise Center of the UMCG is at the forefront of research on giant cell arteritis.  Our groups publishes in high impact journals in the field of rheumatology and internal medicine 1-10.

  1. Stone JH, Tuckwell K, Dimonaco S, et al. Trial of Tocilizumab in Giant-Cell Arteritis. N Engl J Med. 2017;377(4):317-328. doi: 10.1056/NEJMoa1613849 [doi].
  2. van der Geest KSM, Sandovici M, Brouwer E, Mackie SL. Diagnostic Accuracy of Symptoms, Physical Signs, and Laboratory Tests for Giant Cell Arteritis: A Systematic Review and Meta-analysis. JAMA Intern Med. 2020. doi: 10.1001/jamainternmed.2020.3050 [doi].
  3. Dejaco C, Brouwer E, Mason JC, Buttgereit F, Matteson EL, Dasgupta B. Giant cell arteritis and polymyalgia rheumatica: current challenges and opportunities. Nat Rev Rheumatol. 2017;13(10):578-592. doi: 10.1038/nrrheum.2017.142 [doi].
  4. Graver JC, Sandovici M, Diepstra A, Boots AMH, Brouwer E. Artery tertiary lymphoid organs in giant cell arteritis are not exclusively located in the media of temporal arteries. Ann Rheum Dis. 2017. doi: annrheumdis-2017-211860 [pii].
  5. van der Geest KSM, Borg F, Kayani A, et al. Novel ultrasonographic Halo Score for giant cell arteritis: assessment of diagnostic accuracy and association with ocular ischaemia. Ann Rheum Dis. 2020;79(3):393-399. doi: annrheumdis-2019-216343 [pii].
  6. Dejaco C, Ramiro S, Duftner C, et al. EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice. Ann Rheum Dis. 2018;77(5):636-643. doi: annrheumdis-2017-212649 [pii].
  7. van der Geest KSM, Sandovici M, van Sleen Y, et al. Review: What Is the Current Evidence for Disease Subsets in Giant Cell Arteritis?. Arthritis Rheumatol. 2018;70(9):1366-1376. doi: 10.1002/art.40520 [doi].
  8. van der Geest KS, Abdulahad WH, Chalan P, et al. Disturbed B cell homeostasis in newly diagnosed giant cell arteritis and polymyalgia rheumatica. Arthritis Rheumatol. 2014;66(7):1927-1938. doi: 10.1002/art.38625 [doi].
  9. van Sleen Y, Sandovici M, Abdulahad WH, et al. Markers of angiogenesis and macrophage products for predicting disease course and monitoring vascular inflammation in giant cell arteritis. Rheumatology (Oxford). 2019;kez034:doi: 10.1093/rheumatology/kez034. doi: kez034 [pii].
  10. Nienhuis PH, Sandovici M, Glaudemans AW, Slart RH, Brouwer E. Visual and semiquantitative assessment of cranial artery inflammation with FDG-PET/CT in giant cell arteritis. Semin Arthritis Rheum. 2020;50(4):616-623. doi: S0049-0172(20)30098-6 [pii].