JDM, which affects just three children in a million, is a serious condition where the immune system attacks the body causing skin rashes and severe muscle weakness.
The new approach, which is part of the pioneering HIGH-5 programme at Great Ormond Street Hospital (GOSH) supported by the National Institute for Health Research GOSH Biomedical Research Centre, brings together genomic, clinical and molecular information to help researchers develop a clearer picture of the characteristics or “phenotype” of rare conditions and understand why patients are affected differently.
The team of researchers, who were based at Arthritis Research UK Centre for Adolescent Rheumatology at GOSH and the UCL Great Ormond Street Institute for Child Health (ICH), found that blood samples from children with JDM contained higher levels of a specific subset of B cells (immature translational B-cells) and increased levels of two proteins that cause inflammation (IFN alpha and TLR7). The more severe the child’s condition, the more B-cells, IFNalpha and TLR7 were present in the blood, and when the children were given treatments for JDM, including methotrexate and prednisolone, the number of B-cells and levels of IFN alpha and TLR7 decreased.
Samples for the study were collected from 68 children with JDM and 23 unaffected children from 17 contributing centres across the UK as part of the JDM Research Group.
This research, which was the first to use the HIGH-5 programme’s in-depth approach to phenotyping, identified INF alpha and TLR7 as promising targets for new therapies for JDM and as important indicators of the conditions severity and the patient’s risk of developing complications. The study's first authors were Meredyth Wilkinson and Christopher Piper .
Professor Lucy Wedderburn study senior author and director of the Centre of Adolescent Rheumatology said, “Our individual genetic codes and exposure to different environments makes all patients at GOSH different - even if they have the same condition. A deeper understanding of these differences through in-depth phenotyping like that in the HIGH-5 programme can help us develop more personalized therapies for patients with complex conditions. This project has identified two exciting new targets for future JDM therapies and illustrates the great potential of potential of deep phenotyping methods for research into childhood rare diseases.”
The study was published in Frontiers in Immunology.