Research into childhood myositis.
Diseases that cause inflammation of the muscles (known as myositis) are rare but serious. The most common form of childhood myositis is juvenile dermatomyositis (JDM). JDM affects about 3 children in every million. Because myositis in children is so rare there is a lack of evidence for best ways to treat it. To overcome, this in the UK, a network of researchers, scientists, nurses, physiotherapists and doctors who work with children with myositis agreed to work together, and this has led to a large, powerful collection of cases of childhood myositis each with data and samples stored. This study is called the Juvenile Dermatomyositis Cohort Biomarker Study and Repository (UK and Ireland) (JDCBS). In the past a research bottleneck existed due to a lack of adequate standardized clinical data linked to biological samples in sufficient numbers for research: collaborative networks such as this directly address this need. It is therefore seen to be a highly valuable resource for research by researchers in the field and has already been used to make several breakthrough discoveries in myositis. The JDCBS has recently been awarded peer reviewed grant funding from several bodies including the Wellcome Trust and Action Medical UK. The Chief Investigator of the JDCBS is Dr Lucy Wedderburn Institute of Child Health UCL London. The JDCB study has full ethical approval and all children and families are recruited with informed consent. All the data are stored in an anonymous fashion in a secure, protected database with full security and compliant with the Data Protection Act. New projects or proposals may require amendment or extension to the existing ethical approval as appropriate.
Projects already started or published which have been made possible through the existence of the JDCBS have included studies on clinical treatments, physiotherapy, new drugs for JDM, the best way to analyse muscle biopsy tissue from children with JDM, antibodies in JDM and how they relate to immune system (HLA) genes affecting the subtype of myositis, as well as other genes that may play a role in JDM, how blood vessels may be altered in JDM and many others. For more details on current and previous projects please see below.
The JDRG and the JDCBS and how it works
The group of researchers involved in the JDCBS study and the work within it, are called the Juvenile Dermatomyositis Research Group (JDRG). The centres involved in the JDRG are from all around the UK and all have specialist Paediatric Rheumatology teams working in the field. See About JDRG
Each centre has several involved individuals, including a Principle Investigator (PI), who is usually the doctor seeing the children with myositis, and also other staff such as nurses, physios or others who care for and work with children with JDM and other forms of myositis. The JDRG meets on an annual basis to discuss progress, projects, ideas and how the study can help improve the lives of children with myositis.
Members of the JDRG are involved in many projects for research. New centres that are able to contribute data and recruit families to join this cohort are always welcome and interested centres should first contact the JDRG Administrator at info@jdrg.org.uk
Are you interested to know more or propose a research project?
In addition to members of the JDRG, researchers who are interested in myositis are very warmly encouraged to contact the JDRG and JDCBS about possible projects, or collaborations. The JDCBS is run by a steering committee, which includes an independent chair (Dr M Friswell) and advisors, and also patient/parent representation. One of the key roles of this Steering Committee is to consider all collaborations and applications for use of the JDCBS data and or samples. Each research project requesting to use the Cohort study usually needs to obtain research funding and may need to obtain specific amendments to existing ethical approvals. If you are a researcher or interested party and would like to know more about the JDCBS and the application procedure to the Steering Committee please contact the JDRG Administrator at info@jdrg.org.uk
Recent projects
Specific studies which have been made possible by the existence of the UK and Ireland Juvenile Dermatomyositis Cohort Biomarker Study and Repository, include:
1. Immunological characterisation of the infiltrate in JDM muscle
2. Tracking of lymphocyte changes before or after flare of active disease
3. Analysis of MHC Class 1 expression in an animal model of myositis
4. Autoantibodies in Juvenile Dermatomyositis, Scleroderma and overlap syndromes
5. HLA Haplotype analysis in JDM and correlation with serotype
6. Recognition of MHC Class 1 molecules on muscle cells by NK cells or CD8 lymphocytes
7. The role of muscle ultrasound and MRI in juvenile dermatomyositis
8. Assessment of JDM disease activity by MRI pre and post exercise
9. The Role of Cyclophosphamide in treatment of JDM
10. Role of Infliximab in treatment of JDM
11. Investigation of alterations of MRP8/14 proteins in juvenile dermatomyositis
12. Do functional gene variants in anti-inflammatory pathways alter the course of disease and allow greater inflammatory response?
13. Fetuin-A and calcinosis in Juvenile dermatomyositis
14. Genotyping analysis in JDM for phenotype: genotype correlation
15. Is there evidence of maternal microchimerism in muscle biopsies from children with Juvenile Dermatomyositis?
16. Contribution to a world wide collaboration (MYOGEN) for a genome wide association study of myositis
17. The vasculopathy of juvenile dermatomyositis
18. Ongoing contributions to the PRINTO study: http://www.printo.it/project ongoing.asp
19. Ongoing contributions to IMACS myositis studies, including classification of myositis project and others see https://dir-apps.niehs.nih.gov/imacs/
Recent Publications
Publications made possible by the existence of the UK and Ireland Juvenile Dermatomyositis Cohort Biomarker study and Repository:
1. Li, C., Varsani, H., Holton, J. Gao, B., Woo, P., and Wedderburn, L. R. and on behalf of the JDRG (2004). MHC Class I Over-expression on Muscles in early Juvenile Dermatomyositis. J Rheumatology 31, 605- 609
2. Riley, P., Maillard, S. M., Wedderburn, L. R., Woo, P., Murray K. J. and Pilkington, C. A. (2004). Intravenous Cyclophosphamide Pulse Therapy in Juvenile Dermatomyositis - Efficacy And Safety. Rheumatology 43, 491- 496.
3. Maillard, S.M., Jones, R., Owens, C., Pilkington, C. A., Wedderburn, L. R., Woo, P. and Murray, K. J. (2004). Quantitative assessment of MRI T2 relaxation time of thigh muscles in children with dermatomyositis. Rheumatology 43, 603- 608
4. Wedderburn L. R. and Li, C. (2004). The pathogenesis of juvenile idiopathic inflammatory myopathies. Best Practice and Research Clinical Rheumatology 18(3), 345 – 358.
5. Wedderburn, L. R, (2004). Juvenile Dermatomyositis. Arthritis Today (Arthritis Research Campaign) 123, 10-12. Arthritis Research Campaign.
6. Maillard, S.M., Jones, R., Owens, C., Pilkington, C., Woo, P., Wedderburn, L. R., and Murray, K. J. (2005). Quantitative Assessments of the Effects of Exercise on Muscles in Juvenile Dermatomyositis. Arthritis and Rheumatism 53 (4), 558 – 564.
7. Pilkington, C.A. and Wedderburn, L. R. (2005). Paediatric Idiopathic Inflammatory Muscle Disease: Recognition and Management. Drugs 65 (10), 1355 – 1365.
8. Vojinovic J, Riley P, Maillard S, and Pilkington C.A. (2005). Importance of agressive treatment in Juvenile Dermatomyositis. Srp Arh Celok Lek. 133 Suppl 2,118-23.
9. McCann, L.J, Juggins, A., Maillard, S.M., Wedderburn, L. R., Davidson, J. Murray, K. J. and Pilkington, C.A. and on behalf of the Juvenile Dermatomyositis Research Group (JDRG). (2006). The Juvenile Dermatomyositis National Registry and Repository (UK and Ireland): Clinical characteristics of children recruited within the first 5 years. Rheumatology 45, 1255 – 60
10. Brown VE, Pilkington CA, Feldman BM, and Davidson JE. (2006). An international consensus survey of the diagnostic criteria for juvenile dermatomyositis (JDM). Network for Juvenile Dermatomyositis, Paediatric Rheumatology European Society (PReS). Rheumatology. 45: 990-3.
11. Wedderburn L.R, Varsani, H., Li, C.K.C., Newton, K. R., Amato, A.A., Banwell, B., Bove, K. E., Corse, A.M., Emslie-Smith, A., Harding, B., Hoogendijk, J., Lundberg, I.E., Marie S.K., Minetti C., Nennesmo I., RushingE.J., SewryC., Allen E, Charman, S.C., Pilkington,C.A., Holton, J. (the International Consensus Group on JDM Biopsy), and on behalf of the UK Juvenile Dermatomyositis Research Group (JDRG). (2007). International consensus on a proposed score system for muscle biopsy evaluation in patients with JDM, for potential use in clinical trials. Arthritis and Rheumatism 57,1192-1201
12. McCann LJ, Garay SM, Ryan MM, Harris R, Riley P, Pilkington CA. (2007). Oropharyngeal dysphagia in juvenile dermatomyositis (JDM): an evaluation of videofluoroscopy swallow study (VFSS) changes in relation to clinical symptoms and objective muscle scores. Rheumatology 46,1363-6.
13. Wedderburn, L.R., McHugh, N. J., Chinoy, H., Cooper, R G., Salway, F., Ollier, W.E.R., McCann, L., Varsani, H., Dunphy, J., North, J., and Davidson, J. and on behalf of the Juvenile Dermatomyositis Research Group (JDRG). (2007). HLA haplotype and autoantibody associations in children with juvenile dermatomyositis, and scleroderma overlap. Rheumatology 46, 1786-1791.
14. McCann, L.J., Li, C.K.C., Varsani, H., Wedderburn, L. R., and Pilkington, C.A. (2007). Failure to over express MHC class l on muscle biopsy in a case of amyopathic juvenile dermatomyositis. Clin Exp Rheumatology 25, 96-8.
15. Marhaug, G., ShahV., Shroff, R., Varsani, H., Wedderburn, L. R., Pilkington, C. A., and Brogan, P. A. (2008). Age dependent inhibition of ectopic calcification: A possible role for Fetuin-A and Osteopontin in patients with Juvenile Dermatomyositis with Calcinosis. Rheumatology. 47, 1031-1037.
16. Riley P, McCann LJ, Maillard SM, Woo P, Murray KJ, and Pilkington CA (2008). Effectiveness of infliximab in the treatment of refractory juvenile dermatomyositis with calcinosis. Rheumatology. 47, 877-80.
17. Elst , E.F., Klein , M., de Jager, W., Kamphuis , S. Varsani, H. Wedderburn, L. R. et al. (2008). Heat Shock Protein 60 in Inflamed Muscle Tissue is the Target of Regulatory Auto Reactive T cells in Patients with Juvenile Dermatomyositis. Arthritis and Rheumatism 58, 547 – 555.
18. Gunawardena H, Wedderburn LR, North J, Betteridge Z, Dunphy J, Chinoy H, Davidson JE, Cooper RG, McHugh NJ, and the Juvenile Dermatomyositis Research Group UK. (2008). Clinical associations of autoantibodies to a p155/140 kDa doublet protein in juvenile dermatomyositis. Rheumatology 47, 324 – 328.
19. Varsani, H., Newton, K. R., Li, C. K., Harding, B., Holton, J., and Wedderburn, L. R. (2008). Quantification of normal range of inflammatory changes in morphologically normal pediatric muscle. Muscle and Nerve 37, 259- 61.
20. Chinoy, H., Platt H., Lamb, J. A., Z. Betteridge, Z., Gunawardena H., Fertig, N., Varsani, H., Davidson, J. Oddis, C. V., McHugh, N. J., Wedderburn, L. R., Ollier, W. E. R., and Cooper R. G., UK Adult Onset Myositis Immunogenetic Collaboration and the Juvenile Dermatomyositis Research Group. (2008). The PTPN22 gene is associated with juvenile and adult UK Caucasian idiopathic inflammatory myopathy independent of the HLA 8.1 haplotype. Arthritis & Rheumatism 58, 3247-325.
21. Salomonsson, S., Grundtman, C., Zhang, S-J., Lanner, J., Li, C., Katz, A., Wedderburn L. R., Kanneboyina N., and Lundberg, I.E. (2009). Up-regulation of MHC class I in transgenic mice results in reduced force-generating capacity in slow-twitch muscle. Muscle and Nerve 39, 674-82.
22. Apaz MT, Saad-Magalhães C, Pistorio A, Ravelli A, de Oliveira Sato J, Marcantoni MB, Meiorin S, Filocamo G, Pilkington C, Maillard S, et al. (2009). Health-related quality of life of patients with juvenile dermatomyositis: results from the Pediatric Rheumatology International Trials Organisation multinational quality of life cohort study. Arthritis and Rheumatism, 61, 509-17.
23. Chinoy,H., PayneD., Poulton,K., Fertig,N., Betteridge,Z., Gunawardena,H., Davidson,J. E., Oddis,C. Wedderburn,L.R., McHugh,N.J., Ollier,W. E., Cooper R. G (2009). HLA-DPB1 associations differ between DRB1*03 positive anti-Jo-1 and anti-PM-Scl antibody positive idiopathic inflammatory myopathy. Rheumatology (Oxford) 48(10), 1213-1217.
24. Gunawardena,H., Wedderburn,L.R., Chinoy,H., Betteridge,Z.E., North,J., Ollier,W.E.R., Cooper,R.G., Oddis,C.V., Ramanan,A.V., Davidson,J.E., Mchugh,N.J. (2009). Autoantibodies to a 140-kd Protein in Juvenile Dermatomyositis Are Associated With Calcinosis. Arthritis and Rheumatism 60(6), 1807-1814
25. Li, C. K., Knopp, P., Moncrieffe, H., Singh, B., Shah S., K Nagaragu, K. Varsani, H., Gao, B., and Wedderburn. L. R. (2009). Over expression of MHC class l heavy chain protein in young skeletal muscle leads to severe myositis: implications for juvenile myositis. American Journal of Pathology. 175:1030-40.
26. Juvenile dermatomyositis: extra-muscular manifestations and their management. Lowry C. A. and Pilkington C. A. (2009) Curr Opinion Rheumatology, in press
27. Wedderburn L. R. and Rider, L.G Juvenile Dermatomyositis: New Developments in Pathogenesis, Assessment and Treatment. (2009). Best Practice and Research in Clinical Rheumatology, 25(3), 665-678.