Juvenile idiopathic arthritis


Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood, with a prevalence of 1 in 1000 and affecting approximately 12000 children in the UK. The clinical phenotype of JIA is complex and outcome is variable. JIA can lead to both short-term and long-term disability with disease persisting into adulthood in up to a third of cases. The causes of JIA are not fully understood but family and twin studies suggest that there is a genetic component to the disease. Identification of the genes involved in JIA may help our understanding of the underlying pathology of the disease which in turn may lead to the development of new therapies. Genetics may also provide useful tools for clinicians in terms of better classification of this complex disease and in predicting outcome.

Research Programme

  1. Identification of the genes associated with susceptibility to JIA. JIA is a very heterogeneous disease comprised of multiple different subtypes. By understanding more about the genes involved in causing JIA it may be possible to identify the key pathways involved in inflammation and how they vary between individuals. This in turn may help better define the underlying subtypes of disease and enable a more targeted approach to therapy.
  2. Identification of the genetic and genomic factors that predict outcome (including treatment response) in JIA. The long-term outcome for children with JIA is unclear but estimates suggest up to 70% of children will continue to be affected in to adulthood. There is also significant variability in terms of outcome and treatment response both between and within the different JIA subtypes. There are currently no robust clinical or biological predictors of outcome; the aim of this programme is to address this issue using a combination of clinical, psychological, genetic and genomic approaches.
    Outcomes studied include:
         a. disability
         b. pain
         c. treatment response

Cohorts available

JIA susceptibility.  Our JIA susceptibility studies are facilitated by two cross sectional cohort studies.

The British Society for Paediatric and Adolescent Rheumatology (BSPAR) National Repository for JIA

The repository is a cross-sectional cohort of JIA cases collected from across the UK via members of BSPAR. It contains DNA, serum and cross sectional clinical data on over 1000 children (and in some cases their parents). The initial collection is closed but has recently been reopened as the UKJIAGC.

Portfolio id:  7881

UK JIA Genetics consortium (UKJIAGC)

UKJIAGC is a new collection of a cross-sectional cohort of JIA cases from the UK. Clinical data as well as DNA and serum are collected. JIA GCUK Recruiting Centres: Aberdeen Royal Infirmary, Freeman Hospital, Great Ormond Street Hospital for Sick Children, London Nuffield Orthopaedic Centre Royal Hospital for Sick Children, Edinburgh Royal, Liverpool Children's Hospital, Alder Hey, Royal Victoria Infirmary Newcastle and University College London Hospital.

Portfolio id:  7881


JIA Outcome. Our outcome studies are facilitated by the Childhood Arthritis Prospective Study (CAPS) a long-term outcome inception cohort study of children with childhood onset inflammatory arthritis.

Portfolio id: 2635

Treatment Response. Our treatment response studies are facilitated via three studies.

In collaboration with Professor Lucy Wedderburn at UCL, the Childhood response to medication study (CHARMS) was set up to identify the clinical, psychological and genetic factors that predict how a child will respond to methotrexate (MTX).

Portfolio id: 3227


Biologics for Children with Rheumatic Diseases (BCRD) - This prospective observational cohort study aims to recruit all children with Juvenile Idiopathic Arthritis who are starting therapy with a biologic drug. A parallel cohort of children starting Methotrexate will also be collected. All children will be followed for a minimum of 5 years. The response to treatment will be assessed at regular intervals using the American College of Rheumatology (ACR) JIA core outcome variables, including active and joint counts, inflammatory markers, pain and disability levels.

Portfolio id: 7725


The BSPAR Etanercept cohort study (BECS) collects detailed information on the effectiveness and safety of Etanercept in children with JIA. A parallel group of children with JIA treated with Methotrexate is also being recruited in order to compare side effects and long term outcomes between the two treatment groups.

Portfolio id: 13553



Name Institute
Lucy Wedderburn Institute of Child Health, University college London, UK
Sue Thompson Division of Rheumatology, Cincinnati Children’s Hospital Medical Center, Cincinnati, USA
Mike Ombrello NHGRI, NIH, Bethesda, MD, USA
Ele Zeggini Wellcome Trust Sanger Institute, Cambridge, UK
JACI consortium members:

Carl Langefeld
Sampath Prahal
Johannes Peter Haas

Wake Forest School of Medicine, Winston-Salem, USA
Emory University School of Medicine, Atlanta USA
German Centre for Rheumatology in children and Young People, Garmisch-Partenkirchen, Germany


Research Summary

  • Early candidate gene based studies investigating regions of the genome which show genetic association in other autoimmune diseases, such as RA, identified key JIA susceptibility loci such as PTPN22 and IL2RA
  • We provided a cohort for validation of JIA positive associations identified in a USA JIA Genome-wide association studies (GWAS) which identified PTPN2 as a susceptibility loci
  • Using an autoimmune loci array (Immunochip), a  recent landmark genetic study in a large international cohort of JIA identified 17 disease susceptibility loci at genome-wide significance, 14 of these for the first time
  • A European consortium investigating response to methotrexate (MTX) in JIA performed a GWAS and found novel genomic regions contributing to MTX response


Contacts/Principal investigators