Role of Epstein-Barr virus in autoimmune diseases, impact of consensus treatment plans, and the search for biomarkers for juvenile arthritis.
References1. Harley JB, Chen X, Pujato M, et al. Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity. Nat Genet. 2018;50:699-707. doi: 10.1038/s41588-018-0102-3.2. Ringold S, Nigrovic PA, Feldman BM, et al. The Childhood Arthritis and Rheumatology Research Alliance consensus treatment plans: toward comparative effectiveness in the pediatric rheumatic diseases. Arthritis Rheumatol. 2018 Jan 15. doi: 10.1002/art.40395.3. New study of over 5,000 children and young people will create biomarker tests to personalise treatment for childhood arthritis [press release]. Cambridge, UK; Medical Research Council; March 28, 2018.
Highlights of 3 new studies in juvenile arthritis include: (1) a protein produced by the Epstein-Barr virus (EBV) activates genes associated with autoimmune diseases, including juvenile idiopathic arthritis (JIA); (2) ongoing consensus treatment plan studies are identifying effective management strategies in pediatric rheumatic diseases; and (3) a landmark consortium plans to transform treatment for juvenile arthritis.1-3
Scroll through the slides for the details of the studies and their clinical implications.
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A protein produced by the EBV, called EBNA2, binds to multiple locations along the human genome that are associated with seven autoimmune diseases. Those diseases are systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, juvenile idiopathic arthritis (JIA), inflammatory bowel disease, celiac disease, and type 1 diabetes. These diseases share a common set of abnormal transcription factors, each affected by the EBNA2 protein.
Using a new computational and biochemical technique known as the Regulatory Element Locus Intersection algorithm, a large collection of genetic and protein data from healthy individuals was compared with data from patients with autoimmune diseases.1 The algorithm identified regulatory regions in genes associated with the risk of developing lupus that also bound EBNA2 and its related transcription factors.
Clinical implications: “Because EBV is most often encountered in early childhood, avoiding infection is practically impossible. However, now that we understand how EBV infection may contribute to autoimmune diseases in some people, researchers may be able to develop therapies that interrupt or reverse this process,” said Daniel Rotrosen, MD, director of the Division of Allergy, Immunology and Transplantation at National Institute of Allergy and Infectious Diseases.
The Childhood Arthritis and Rheumatology Research Alliance has developed consensus treatment plans as a comparative effectiveness tool for research in pediatric rheumatology.
Consensus treatment plans have been published for 8 different diseases and disease manifestations, including for juvenile localized scleroderma, systemic JIA, polyarticular JIA, dermatomyositis, and lupus nephritis.2 Largeâscale studies are underway for systemic JIA and polyarticular JIA.
Results from these studies will provide more information on the feasibility of this approach and may provide insights on which therapeutic strategies are most likely to be successful for certain patients.
Clinical implications: “The consensus treatment plan approach will be even more powerful when coupled with biospecimen collection to facilitate translational research aimed at identifying biomarkers of response and non-response, paving the way toward personalized medicine,” said lead author Sarah Ringold, MD, MS, of Seattle Children’s Hospital in Washington.
A 5-year study of more than 5000 patients with juvenile arthritis plans to create biomarker tests to personalize treatment.
The Medical Research Council-funded study of juvenile arthritis and associated uveitis aims to foster a better understanding of how to treat this complex condition.3
The trial will try to identify a simple biomarker test that will pave the way for new treatment options with fewer adverse effects; help physicians define the appropriate medication for the appropriate duration for each patient; identify which children are at risk for uveitis, which affects 15% of those with juvenile arthritis; and project long-term outcomes for these young patients.
Clinical implications: “Using a stratified medicine approach could be a game changer in childhood arthritis and its associated uveitis. A biomarker test could lead to methods for accurately predicting the right treatment for the right duration, halting the worsening of symptoms and leading to shorter time to remission. Nothing like that has been done before in this area of research,” said lead researcher Professor Lucy Wedderburn of the UCL Great Ormond Street Institute of Child Health, London, UK.