ESR 9: Characterize the molecular pathways activated during the pre-clinical phase of  spondyloarthritis – POSITION FILLED

PhD research

Host:

Dr Marleen van de Sande

Rheumatologist| Assistant professor| PhD

Amsterdam University Medical Centers (location AMC)

Meibergdreef 9

105AZ  Amsterdam

The Netherlands

Duration: 48 months

Background

Axial spondylitis (axSpA) is the second most prevalent type of chronic inflammatory arthritis. In the pathogenesis of axSpA innate immune triggering at a site distant of the joint (e.g. gut, skin) results in clinical manifest disease with axial inflammation and new bone formation. With the current available treatments only about 20% of the axial spondyloarthritis patients achieve remission, and new bone formation cannot be prevented. This results in irreversible structural damage of the spine with functional impairment. Possibly the current treatments do not target the right pathologic processes, or treatment is started too late. Our recent findings evaluating treatment effect of anti-IL23R in the HLA-B27 transgenic rat model of spondyloarthritis suggest that IL-23 plays a role in pathogenesis before onset of clinical manifest disease, but not thereafter. We propose that in the pre-clinical phase, before axSpA becomes clinically manifest, specific immune pathways are activated that subsequently trigger chronic inflammation and irreversible structural damage. We have the opportunity  to molecular characterize the pre-clinical phase in great detail in   biosamples collected in an unique inception cohort of first-degree relatives of HLA-B27 positive axSpA patients at risk of development of disease as well as in the SpA-like HLA-B27 transgenic rat model. This innovative approach allows for in depth analysis of pathways related to inflammation and new bone formation in key target tissues in the preclinical phase of disease and to translate findings from experimental models to the clinic.

Approach 

Key objectives are : 1. Identifying molecular pathways activated during the pre-clinical phase in our heat-inactivated Mycobacterium tuberculosis accelerated HLA-B27 transgenic ratmodel.  2. Investigating whether the identified pathways are also present when other immune triggers more relevant to human spondyloarthritis are applied. 3.  Confirm identified pathways in individuals at risk of developing spondyloarthritis.

Our research team

It is our ambition to elucidate the pathways that initiate chronic inflammation and new bone formation from the earliest phases of spondyloarthritis onwards. Findings from our studies will lead to the identification of potential novel treatment targets aiming for remission or even prevention of structural damage to improve outcome and quality of life for spondyloarthritis patients. We work within the Amsterdam Rheumatology and immunology Center (ARC), are embedded in the Amsterdam Infection & Immunity Institute, and  have access to high quality core research facilities of the AMC including e.g. the Animal house, Bio-informatics Laboratory.  This provides an excellent multidisciplinary research environment which form a basis for fruitful scientific collaborations between clinicians and basic scientists on our translational research projects.  The van de Sande group currently consists of 1 PhD student, 2 research nurses, and 1 supportive personnel. This project will be performed in close collaboration with ARCAID PI’s dr. Lisa van Baarsen (transciptomics) and prof. dr. Antoine van Kampen (bioinformatics), as well with our postdocs experienced in animal models.