Inflammatory Muscle Disease Group
Leader: Professor Lucy R Wedderburn
- Ms Katie Arnold, JDRC administrator
- Ms Laura Kassoumeri, research study coordinator
The Wedderburn group has a major interest in the pathology of muscle damage in childhood inflammatory myositis. This work is closely linked to our work through the Juvenile Dermatomyositis Cohort and Biomarker Study and the Juvenile Dermatomyositis Research Centre.
Our early work showed that expression of MHC class l in JDM can predate inflammation and may itself cause muscle damage. Using a novel murine model, we showed that early over expression of MHC in very young muscle rapidly precipitates ER stress and muscle dysfunction. To translate this understanding of muscle pathology to patients, we formed the International JDM Biopsy Consensus Group, in collaboration with colleagues across UCL and from around the world: we have designed and tested a histological score system, now being prospectively validated.
In parallel our work on JDM genetics and auto-antibodies has shown strong association between HLA genotype and serological phenotype in JDM as well as other new genetic associations. In collaboration with Prof N McHugh (Bath University) we have found several novel autoantibodies, which distinguish clinical subtypes of JDM.
Our current work focuses on the role of S100 proteins S100A8/A9 (also known as myeloid related proteins) in the pathology of JDM, and the activity of stem cells, known as satellite cells in JDM muscle pathology.
The Juvenile Dermatomyositis Research Centre (JDRC) was founded in July 2000 through a charitable donation from the Cathal Hayes Research Foundation. The JDRC hosts the JDM Cohort and Biomarker Study (UK and Ireland), one of the largest collections of data and samples from children with JDM in the world. The study includes a network of researchers and clinicians know as the Juvenile Dermatomyositis Research Group (JDRG). The work of the JDRC and JDRG brings together a number of multidisciplinary health care professionals, scientists and others undertaking research into juvenile dermatomyositis (JDM) and other forms of inflammatory myositis in children. This expertise, combined with that of the JDRC's collaborative partners, has already lead to an increased understanding of the onset, course, prognosis and outcome of this and related diseases, with consequent improvements in prevention, management and, ideally, curative treatments. The JDRG involves nine centres in total across the UK, and attracts many collaborative projects. The staff within the centre also administrate the European Network for Juvenile Dermatomyositis, which is a forum of specialists in this illness. The organisation aims to encourage research collaborations, essential to studying this rare disease. More information about research projects involved in this Network can be found on the JDRG website
Recent projects have included a major genotype/phenotype study of HLA genetics and serology in JDM, a biopsy study which generated a score tool with which to measure abnormality in JDM Biopsy (including the forming of the International Consensus Working Group in JDM Biopsy), the study of over expression of MHC class I heavy chain protein on muscle fibres early in the myositis process, and a study of the effects of exercise on muscle in JDM.
Juvenile Dermatomyositis (JDM) Cohort and Biomarker Study (UK and Ireland) Established and administered by the JDRC, this is a large database of detailed clinical records on JDM patients, together with a Biobank serum, tissue and DNA samples. C Pilkington, LR Wedderburn, L Beard, H Varsani, and S Maillard. Click here to go to the JDCBS Website.
A mechanism-based approach to genotype/phenotype associations in JDM and subtypes of JDM We have completed a large study of HLA genotyping correlated with detailed serology in JDM and JDM-scleroderma overlap in collaboration with N McHugh, H Gunawardena, B Cooper and H Chinoy
We have analysed genetics of several novel candidate genes in JDM including PTPN22. We are now contributing to a genome wide-association study (GWAS) of myositis which includes both adults and children. H Varsani and LR Wedderburn
International Consensus Working Group in JDM Biopsy: generation of a scoring tool for use in assessing abnormality in JDM Biopsy This international group of experts on muscle biopsy has generated and validated a score tool with which to measure abnormality in JDM biopsy, which will now being prospectively tested in cohorts from several countries. LR Wedderburn, H Varsani, J Holton, C Pilkington and S Charman. With the International Consensus Group on JDM Biopsy
The role of MHC class l over expression in muscle damage in JDM A detailed molecular study of the MHC over expression, both in patients and model systems in the laboratory. Recent work using a novel model of myositis showed that early over expression of MHC in very young muscle rapidly precipitates ER stress and muscle dysfunction which may explain some features of severe JDM and how it differs from adult DM. LR Wedderburn, H Varsani
Satellite cell biology in a novel model of juvenile dermatomyositis A study of the role and function of satellite cells in paediatric muscle from JDM patients and healthy children. H Varsani LR Wedderburn
Investigation of the pathogenic mechanisms of juvenile dermatomyositis (JDM). In this study we will be testing and validating the score tool for JDM biopsy and investigating which pathological mechanisms correlate with clinical course severity or outcome. H Varsani, and LR Wedderburn. In collaboration with J Holton and the International Consensus Group on JDM Biopsy
The vasculopathy of JDM This study aims to investigate changes in endothelial biology in JDM and their impact upon disease subtype or severity. P Brogan, L Wedderburn, C Pilkington. You can see more information on this study on the Vasculitis group page.
European Network for Juvenile Dermatomyositis. This organisation, administered from the JDRC, is an ongoing forum for clinicians and scientists working in these diseases and is designed to foster and facilitate research and collaboration. C Pilkington, LR Wedderburn, and J Davidson
Quantitative and qualitative assessment of the effects of exercise on muscles in children with juvenile dermatomyositis Controlled, prospective physiotherapy-led project using MRI and muscle enzyme levels to assess effects of exercise on muscle which has shown that there are no short term damaging effects on muscle in children with JDM. S Maillard, C Pilkington, LR Wedderburn
International Myositis Outcome Assessment Collaborative Study Group An international project to develop validated indices to assess activity and damage in children and adults with myositis. Click here to go to the IMACS website.
Members of the JDRC are also contributing to international clinical studies in JDM including:
PRINTO study of JDM. Click here to go to the PRINTO website about this study.
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