Tissue research in childhood inflammatory arthritis (TRICIA consortium)

Lead Research Organisation: University of Birmingham
Department Name: Institute of Inflammation and Ageing


Childhood arthritis affects 1 in 1000 children and young people and is called Juvenile Idiopathic Arthritis (JIA). We now know that early and intensive treatment of JIA reduces the risk of long-term joint damage and increases the likelihood that arthritis will be sufficiently controlled to allow treatment to be stopped in the future. However, JIA can present in many different ways: while some children already have severe arthritis at the time of diagnosis, others have a mild form of arthritis limited to the involvement of a small number of joints. Some of these children will go on to develop severe arthritis, while in others, the arthritis improves with only simple medications such as ibuprofen. At present we cannot predict which children will go on to develop severe arthritis or which children will respond to certain types of drugs. Thus, a major barrier to developing a 'precision approach' to treatment in JIA is the ability to identify which children require treatment and who is likely to respond to which type of drug.
To date, the majority of research in JIA to address this unmet need has been carried out on either blood samples or joint fluid, due to difficulties in accessing the site of the disease itself - the synovial tissue (joint lining), and therefore do not reflect accurately pathology in the joint. We have pioneered the use of a minimally invasive, safe and well-tolerated technique to obtain small pieces of synovial tissue or 'synovial tissue biopsies' in adults with rheumatoid arthritis (RA). These studies have transformed our understanding of disease in RA and led to new therapy targets and biopsy driven pathology led treatment stratification trials. No such studies exist in JIA.
We are currently performing the first synovial biopsy-based studies in JIA as part of a collaborative network between Birmingham, University College London and Oxford (MAPJAG study). While JIA is phenotypically and biologically distinct from RA, the availability of safe, effective, synovial biopsy techniques that can be repeated longitudinally in routine NHS surroundings has the potential to deliver a paradigm shift in our understanding of disease pathology, biomarker discovery and the development of therapeutic targets in JIA. The rarity of JIA compared to RA means it is necessary to expand our existing network to support studies that are sufficiently powered, with appropriate numbers of cases to address important research questions.
In this partnership we propose to build capacity within UK paediatric rheumatology to perform ultrasound-guided synovial tissue biopsies as part of clinical research and bring these studies together to form a unique Consortium, called the Tissue Research in Childhood Inflammatory Arthritis (TRICIA). TRICIA will work with all the main stakeholders including clinical and research collaborators, as well as families and patients whose lives are affected by JIA. Importantly, the partnership will form collaborations with other key UK and international consortia initiatives to streamline precision medicine strategies in JIA.
The key aspects of the work planned in the TRICIA Consortium are to:
1. Support the establishment of peadiatric synovial tissue biopsy programs at new centres.
2. Provide training and expertise in performing synovial tissue biopsies in children and young people with arthritis.
3. Collect data on the acceptability, tolerability and safety of the biopsy procedure in a paediatric population.
4. Have a consistent approach to collecting clinical data linked to biological samples.
5. Agree to collect data and tissue samples in the same way in the future.
6. Design and agree a way to share data within a common platform that can be used by researchers to better understand arthritis.

Technical Summary

The primary goal of this partnership is to create the Tissue Research in Childhood Inflammatory Arthritis Consortium (TRICIA), which aims to develop the intellectual infrastructure, workflow pipelines and capacity to deliver multicentre synovial tissue-based studies in children and young people with juvenile idiopathic arthritis (JIA) in the UK. The consortium will build on an existing and funded collaborative network that supports the investigation of synovial pathology in children with JIA. We will bring together UK clinical centres with the capability to perform synovial tissue biopsies and partner with major academic centres performing advanced tissue analytics linked to clinical outcome measures (data science). Our long-term goal is to embed synovial tissue analytics within both multi-centre biopsy driven clinical trials and clinical practice.
The aims of the TRICIA consortium are:
1. To build capability within UK paediatric rheumatology to perform synovial tissue research in JIA by establishing synovial biopsy programmes at new centres.
2. Provide training in minimally invasive, ultrasound-guided synovial biopsy techniques in children and young people.
3. Collect data on the acceptability, tolerability and safety of paediatric synovial tissue biopsies.
4. Establish standardised approaches to clinical and biological data capture.
5. Establish a dedicated tissue analysis pipeline with a standardised approach to synovial tissue collection, processing and analysis.
6. Deposit and present clinical and experimental data from tissue analysis studies in a common integrated platform with web-based knowledge management tools supporting data mining, analysis and hypothesis generation.
The creation of TRICIA and use of harmonised data and sample collection protocols will ensure that the consortium is ideally placed to maximise the benefit from ongoing precision medicine initiatives in JIA and obtain funding for synovial tissue research in the future.


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