MAPJAG: Mechanisms of Joint and Gut Inflammation in Children and Young People
A clinical observation study investigating inflammation in childhood arthritis
MAPJAG is a multi-site, non-interventional study investigating the relationship between joint and gut inflammation in children and young people with juvenile idiopathic arthritis (JIA).
It is the first study of its kind to use minimally invasive synovial biopsy techniques in paediatrics, combined with gut sampling and advanced tissue analysis.
Study Overview
MAPJAG – Mechanisms of Joint and Gut Inflammation in Children and Young People – is designed to enhance our understanding of the biological links between synovial inflammation in the joints and gastrointestinal involvement in JIA. The study provides an unprecedented opportunity to capture high-quality tissue and gut samples from paediatric patients, which can be matched to clinical outcomes over time.
The MAPJAG study aims to:
Investigate whether immune responses in the gut are reflected in joint inflammation, and vice versa
Collect matched synovial biopsy and stool/gut mucosal samples from participants at baseline and during disease progression
Use spatial and molecular analysis to identify cell types, immune markers, and inflammatory patterns
Associate these findings with real-world clinical outcomes, treatment escalation, and disease remission or persistence
What's Involved
Participants in MAPJAG are children and young people under the care of paediatric rheumatology teams who may be undergoing a clinical procedure such as a joint steroid injection. At the same time, they may be invited to:
Provide synovial tissue samples via ultrasound-guided biopsy
Provide stool samples and/or gut mucosal swabs
Complete a brief questionnaire about their symptoms and quality of life
Return for follow-up assessments, including blood tests or repeat sampling where clinically appropriate
All participation is voluntary. No experimental treatments are involved, and each site follows a rigorous, ethically approved protocol designed in consultation with families and healthcare professionals. Children and their families are fully supported by experienced clinical teams trained in both medical care and research delivery.
Where It's Happening
MAPJAG is currently live at several TRICIA-affiliated NHS paediatric rheumatology centres, including:
Birmingham Women’s and Children’s NHS Foundation Trust – the lead site for the MAPJAG study, providing coordination across the network and leading on biopsy training, ethics, and data integration.
Great Ormond Street Hospital for Children NHS Foundation Trust – a key early adopter site actively contributing to participant recruitment and sample collection with a strong translational research infrastructure.
These centres are fully trained in TRICIA’s standardised protocols and play a pivotal role in the delivery and refinement of the study approach.
Additional sites are in various stages of feasibility and training, with the aim of expanding access across the UK.
Analysis and Impact
The MAPJAG study generates high-resolution biological data that can provide a window into how JIA develops and behaves. Samples undergo multi-layered analysis using technologies such as:
Histology and immunostaining to examine cell types and tissue architecture
Spatial transcriptomics to localise gene expression changes within the joint
Metagenomics and microbiome profiling to analyse microbial composition and functional genes in the gut
These data are analysed alongside clinical features such as disease duration, treatment response, and flare frequency. The aim is to identify biomarkers that can inform patient stratification, predict disease trajectory, and ultimately guide targeted treatment strategies for children with JIA.
Study Results and Ongoing Discoveries
The first published results from the MAPJAG study, are available in Science Translational Medicine (July 2025).
This publication presents the first detailed map of the cellular and molecular landscape inside the inflamed joints of children with Juvenile Idiopathic Arthritis (JIA), using cutting-edge techniques like single-cell RNA sequencing and spatial tissue analysis.
Key Findings from the first 19 participants:
- Successfully created the first high-resolution atlas of synovial tissue in children with JIA.
- Identified distinct “niches” of cells within joint tissue, some strongly linked to more severe disease.
- Found specific pro-inflammatory cell types, including SPP1+ macrophages, associated with worsening arthritis.
- Showed that joint tissue is very different from blood or joint fluid, providing crucial insights that cannot be captured by standard blood tests.
- Compared JIA tissue to adult arthritis and found important age-specific differences, underlining why child-focused research is essential.
- These findings will help pave the way towards more personalised treatments, moving beyond a one-size-fits-all approach.
These are preliminary results from the first 19 patients recruited to MAPJAG. The study is continuing, with many more tissue samples already collected and being analysed. More exciting results will follow as we expand our understanding of synovial pathology in childhood arthritis.
You can read the full open-access article here: Europe PMC record for the paper
Cite as – Chrissy Bolton et al., Synovial tissue atlas in juvenile idiopathic arthritis reveals pathogenic niches associated with disease severity.Sci. Transl. Med.17,eadt6050(2025). DOI:10.1126/scitranslmed.adt6050
What families said about taking part
The MAPJAG study was only possible thanks to the children and families who generously agreed to take part and share tiny samples of tissue during planned procedures.
We were keen for her to be involved. Given that she was already having an anaesthetic, and it wasn’t an additional operation for her, it was a great opportunity. We hope the study will help other families with children in similar positions to us
Working with families of children with arthritis opened the door to this study. The families advocated for the potential of the research, agreeing that the procedure would be acceptable to families—especially compared to living with a chronic inflammatory disease
Their brave involvement has helped researchers begin to understand why arthritis treatments affect children differently. Samples collected from young participants offered valuable clues about how inflammation develops inside the joint and how this could lead to more targeted, effective treatments in the future.
Get Involved or Learn More
We welcome questions from families, clinicians, researchers, and partner sites. To learn more about MAPJAG or how to support the study:
The MAPJAG study is adopted into the clinical research network (CRN) portfolio.
Study Information:
Study Title: Mechanisms of Joint Inflammation in Children and Young People with Juvenile Idiopathic Arthritis
IRAS Project ID: 292585
REC Reference: 21/EE/0103
Sponsor: University of Birmingham
Funding:
- Initially established through the Arthritis Therapy Acceleration Programme (A-TAP), funded by the Kennedy Trust for Rheumatology Research. This funding enabled the development of the observational study, laying the groundwork for paediatric synovial biopsy research
- The study later received further support from Versus Arthritis through the Multiomic Analysis of Paediatric Joint and Gut Inflammation (MAPJAG) and;
- The UK Research and Innovation (UKRI) Medical Research Council (MRC) through a Partnership Award. This support strengthens the infrastructure for multi-centre synovial tissue research, ensuring the continued integration of synovial biopsies into clinical trials and routine care.
- This study has been delivered through the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC). The views expressed are those of the author(s) and not necessarily those of the research funders, the NIHR, or the Department of Health and Social Care.