Tissue research in childhood inflammatory arthritis (TRICIA consortium)
Lead Research Organisation:
University of Birmingham
Department Name: Institute of Inflammation and Ageing
Abstract
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.
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.
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.
Organisations
- University of Birmingham (Lead Research Organisation)
- UNIVERSITY OF OXFORD (Collaboration)
- UNIVERSITY OF EDINBURGH (Collaboration)
- University College London (Collaboration)
- University of Manchester (Collaboration)
- UNIVERSITY OF GLASGOW (Collaboration)
- Great North Children's Hospital (GNCH) (Collaboration)
- Newcastle University (Collaboration)
- UNIVERSITY OF BIRMINGHAM (Collaboration)
- Brigham and Women's Hospital (Collaboration)
- Birmingham Children's Hospital (Collaboration)
- Trinity College Dublin (Collaboration)
Publications
![publication icon](/resources/img/placeholder-60x60.png)
Bolton C
(2024)
All fibroblasts are equal, but some are more equal than others.
in Nature reviews. Rheumatology
![publication icon](/resources/img/placeholder-60x60.png)
Hackland A
(2023)
Are the origins of adult arthritis seeded during embryonic development?
in Nature reviews. Rheumatology
![publication icon](/resources/img/placeholder-60x60.png)
Khan AO
(2023)
Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies.
in Cancer discovery
![publication icon](/resources/img/placeholder-60x60.png)
Wedderburn LR
(2023)
Towards molecular-pathology informed clinical trials in childhood arthritis to achieve precision medicine in juvenile idiopathic arthritis.
in Annals of the rheumatic diseases
Title | JIA Patients and Research Importance |
Description | Jasmine and Sophie are two patients who live with JIA and they explain in less than 2 minutes how the condition has impacted their lives and why, in their own words, they think research into JIA and potential treatments is vital. Recorded in March 2024. |
Type Of Art | Film/Video/Animation |
Year Produced | 2024 |
Impact | Patient perspective from young people with JIA is very impactful |
Description | Birmingham Women's and Children's Hospital Charity |
Amount | £15,000 (GBP) |
Organisation | Birmingham Women's and Children's NHS Foundation Trust |
Sector | Public |
Country | United Kingdom |
Start | 11/2022 |
End | 12/2024 |
Description | Daphne Jackson Trust fellowship |
Amount | £150,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 04/2023 |
End | 05/2026 |
Description | Tissue-resident CD8+ memory T cell and fibroblast cross-talk in juvenile idiopathic arthritis |
Amount | £250,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2022 |
End | 09/2025 |
Description | Collaboration with Ellen Gravallese Lab |
Organisation | Brigham and Women's Hospital |
Country | United States |
Sector | Hospitals |
PI Contribution | Provision of spatial transcriptomics data Tissue Histology |
Collaborator Contribution | Pathology expertise and tissue analysis Spatial tissue analysis |
Impact | New tissue scoring system Publication under review |
Start Year | 2024 |
Description | Collaboration with Gentek Lab (Developmental Biology) |
Organisation | University of Edinburgh |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Expertise in genomics |
Collaborator Contribution | Provision of mouse models of macrophage biology for testing in disease context |
Impact | Abstract submitted to EWRR meeting |
Start Year | 2023 |
Description | New study set up |
Organisation | Trinity College Dublin |
Country | Ireland |
Sector | Academic/University |
PI Contribution | Training in synovial tissue biopsy porcedures |
Collaborator Contribution | Patient recruitment Provision of tissue samples |
Impact | New collaboration agreement New training program |
Start Year | 2023 |
Description | New study set up site |
Organisation | Great North Children's Hospital (GNCH) |
Country | United Kingdom |
Sector | Hospitals |
PI Contribution | Technical expertise and training of synovial tissue biopsy |
Collaborator Contribution | Patient recruitment and clinical data |
Impact | Training of clinical fellows Recruitment to study |
Start Year | 2024 |
Description | New study set up site |
Organisation | Newcastle University |
Department | Newcastle Biomedicine |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Technical expertise and training of synovial tissue biopsy |
Collaborator Contribution | Patient recruitment and clinical data |
Impact | Training of clinical fellows Recruitment to study |
Start Year | 2024 |
Description | The role of PRG4 in joint disease |
Organisation | Birmingham Children's Hospital |
Country | United Kingdom |
Sector | Hospitals |
PI Contribution | Clinical samples of synovial tissue taken from individuals with arthopathy. Single cell analysis and advanced tissue analytics of the above samples |
Collaborator Contribution | Glasgow - Provision of genetically altered fibroblasts for comparison Oxford - reagents and imaging BWCH - patient samples |
Impact | Abstract submissions generation of datasets |
Start Year | 2023 |
Description | The role of PRG4 in joint disease |
Organisation | University of Glasgow |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Clinical samples of synovial tissue taken from individuals with arthopathy. Single cell analysis and advanced tissue analytics of the above samples |
Collaborator Contribution | Glasgow - Provision of genetically altered fibroblasts for comparison Oxford - reagents and imaging BWCH - patient samples |
Impact | Abstract submissions generation of datasets |
Start Year | 2023 |
Description | The role of PRG4 in joint disease |
Organisation | University of Oxford |
Department | Kennedy Institute of Rheumatology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Clinical samples of synovial tissue taken from individuals with arthopathy. Single cell analysis and advanced tissue analytics of the above samples |
Collaborator Contribution | Glasgow - Provision of genetically altered fibroblasts for comparison Oxford - reagents and imaging BWCH - patient samples |
Impact | Abstract submissions generation of datasets |
Start Year | 2023 |
Description | Tissue research in Childhood Arthritis |
Organisation | University College London |
Department | Institute of Child Health |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Expertise in synovial tissue biopsies Single cell transcriptomics and advanced tissue analytics Immunology and tissue expertise Functional assays Patient recruitment |
Collaborator Contribution | The aim of the collaboration is to share expertise and University of Manchester - Long term data collection and disease trajectory analysis University of Oxford - data management and multiomics analysis University College London - synovial tissue analysis, patient recruitment, immunology expertise and pathophysiology (functional assays) and |
Impact | Abstracts presented at British Society of Rheumatology annual meeting and Paediatric Rheumatology European Association Supported successful fellowship funding applications for Dr Lizzy Rosser (Kennedy Trust Senior Fellowship), Dr Christine Bolton (Clinical Research Training Fellowship) and Dr Beth Clay (Daphne Jackson Trust fellowship - Medical Research Council, Kennedy Trust). |
Start Year | 2022 |
Description | Tissue research in Childhood Arthritis |
Organisation | University of Birmingham |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Expertise in synovial tissue biopsies Single cell transcriptomics and advanced tissue analytics Immunology and tissue expertise Functional assays Patient recruitment |
Collaborator Contribution | The aim of the collaboration is to share expertise and University of Manchester - Long term data collection and disease trajectory analysis University of Oxford - data management and multiomics analysis University College London - synovial tissue analysis, patient recruitment, immunology expertise and pathophysiology (functional assays) and |
Impact | Abstracts presented at British Society of Rheumatology annual meeting and Paediatric Rheumatology European Association Supported successful fellowship funding applications for Dr Lizzy Rosser (Kennedy Trust Senior Fellowship), Dr Christine Bolton (Clinical Research Training Fellowship) and Dr Beth Clay (Daphne Jackson Trust fellowship - Medical Research Council, Kennedy Trust). |
Start Year | 2022 |
Description | Tissue research in Childhood Arthritis |
Organisation | University of Manchester |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Expertise in synovial tissue biopsies Single cell transcriptomics and advanced tissue analytics Immunology and tissue expertise Functional assays Patient recruitment |
Collaborator Contribution | The aim of the collaboration is to share expertise and University of Manchester - Long term data collection and disease trajectory analysis University of Oxford - data management and multiomics analysis University College London - synovial tissue analysis, patient recruitment, immunology expertise and pathophysiology (functional assays) and |
Impact | Abstracts presented at British Society of Rheumatology annual meeting and Paediatric Rheumatology European Association Supported successful fellowship funding applications for Dr Lizzy Rosser (Kennedy Trust Senior Fellowship), Dr Christine Bolton (Clinical Research Training Fellowship) and Dr Beth Clay (Daphne Jackson Trust fellowship - Medical Research Council, Kennedy Trust). |
Start Year | 2022 |
Description | Tissue research in Childhood Arthritis |
Organisation | University of Oxford |
Department | Kennedy Institute of Rheumatology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Expertise in synovial tissue biopsies Single cell transcriptomics and advanced tissue analytics Immunology and tissue expertise Functional assays Patient recruitment |
Collaborator Contribution | The aim of the collaboration is to share expertise and University of Manchester - Long term data collection and disease trajectory analysis University of Oxford - data management and multiomics analysis University College London - synovial tissue analysis, patient recruitment, immunology expertise and pathophysiology (functional assays) and |
Impact | Abstracts presented at British Society of Rheumatology annual meeting and Paediatric Rheumatology European Association Supported successful fellowship funding applications for Dr Lizzy Rosser (Kennedy Trust Senior Fellowship), Dr Christine Bolton (Clinical Research Training Fellowship) and Dr Beth Clay (Daphne Jackson Trust fellowship - Medical Research Council, Kennedy Trust). |
Start Year | 2022 |
Description | CLUSTER parent champions discussion |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | 48 people in total attended an online workshop with a mixture of patients, children and young people, parents and JIA charity representatives. Discussion of research activities and proposed studies. We discussed current lay material and how it could be improved. I led a discussion on the study design, implementation and recent results in our studies and we discussed how this information could be disseminated to lay audiences. |
Year(s) Of Engagement Activity | 2022,2023 |
URL | https://www.jarproject.org/news/2019/cluster-champions |
Description | PPI Focus Group |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | A focus group with parents and patients to discuss the future direction of tissue research in children and young people. This was held on Friday 1st of December 2023 at the Exchange in Birmingham and was attended by colleagues across the project team (UCL, GOSH, Oxford, University of Birmingham, and Birmingham children's Hospital). |
Year(s) Of Engagement Activity | 2023 |
Description | Patient research partner workshop |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Organised and chaired a patient research partner training sessions on treatment refractory rheumatoid arthritis as part of the Versus Arthritis Centre for Research into Inflammatory Arthritis https://www.race-gbn.org/. |
Year(s) Of Engagement Activity | 2022 |
Description | The Inaugural Lecture of Professor Adam Croft |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Prof Adam Croft Inaugural Lecture on Wednesday 6th of March 2024, outlined the importance of research into juvenile idiopathic arthritis, how Adam came to be involved and the future direction he intends to take. The lecture included videos made by young people who live with JIA and why they want to see more research. The lecture was in person in Birmingham but it could also be watched online in real-time. The audience included academics (national and international), clinicians (national and International as well as parents, families and patients. |
Year(s) Of Engagement Activity | 2024 |
URL | https://www.birmingham.ac.uk/university/colleges/mds/events/2024/03/inaugural-lecture-of-professor-a... |