Juvenile Dermatomyositis Cohort Biomarker Study and Repository (UK and Ireland) (JDCBS)
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 Professor 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.
Haematoxylin and Eosin staining on a patient with JDM versus a control
MHC Class I staining in the muscle of a patient with JDM versus a control
These slides show staining on muscle of a JDM patient
Neonatal myosin Macrophages
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 (Mr Ian Roberts) 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 email@example.com
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
19. Ongoing contributions to IMACS myositis studies, including classification of myositis project and others
20. The effectiveness of anti-TNF alpha agents in the treatment of reftractory Juvenile Dermatomyositis
21. The role of regulatory T cells in the pathogenesis of active Juvenile Dermatomyositis.
22. Establishing early markers of severe disease in Juvenile Dermatomyositis (JDM).
23. Regulatory and effector B cell function in childhood rheumatic disease.
24. To assess fatigue in children with JDM.
25. A survey of current practice in JDM throughout the UK and Ireland.
26. Inclusion body myositis: The 'Alzheimer's disease of muscle' - a diagnostic challenge.
27. Proposal for an international minimal data set for JDM
28. Effectiveness of cyclophosphamide in the treatment of JDM
29. Validation of a new questionnaire for patients and children.
30. Testing of three new skin assessment tools for JDM.
31. The relationship between foot position and muscle strength in JDM
Publications - from most recent, click on the title to open.
Publications made possible by the existence of the UK and Ireland Juvenile Dermatomyositis Cohort Biomarker study and Repository:
Nistala, K., Wedderburn, L.R., (2013) Update in Juvenile
Dermatomyositis. Current Opinion in Rheumatology. Accepted August 2013
Varsani, H., Charman S. C. Li, C.K., Marie, S.,
Amato, A.A. Banwell, B., Bove, K.E., Corse, A.M., Emslie-Smith, A., Jacques,
T.S., Lundberg, I.E., Minetti, C., Nenesmo, I., Rushing, E.J., Sallum, A.M.,
Sewry, C., Pilkington, C.A., Holton, J.A., Wedderburn L.R and the UK JDRG. (2013)Validation
of a score tool for measurement of pathological severity in juvenile
dermatomyositis and correlation with clinical severity of disease.Annals
Rheum Dis epub ahead of print doi:
Nistala, K., Varsani,H., Wittkowski, H., Volg, T., Krol
P., Shah, V., Mamchaoui K. Brogan, P.,
Roth, J., and Wedderburn, L. R. (2013) Myeloid related proteins induce muscle
derived inflammatory mediators in Juvenile Dermatomyositis. Arthritis Res
Therapy Sept;15(5) R131
D, Pistorio A, Palmisani E, Miettunen P, Ravelli A, Pilkington C,
Wulffraat NM, Malattia C, Garay SM, Hofer M, Quartier P, Dolezalova P, Penades
IC, Ferriani VP, Ganser G, Kasapcopur O, Melo-Gomes JA, Reed AM, Wierzbowska M,
Rider LG, Martini A, Ruperto N; for the Paediatric Rheumatology International
Trials Organisation (PRINTO). The PRINTO criteria for clinically inactive
disease in juvenile dermatomyositis.
Ann Rheum Dis 2013;72:686–693.
S.L., McHugh, N.J., and Wedderburn, L.R. (2013) Adult and Juvenile
Dermatomyositis: are the distinct clinical features explained by our current
understanding of serological subgroups and pathogenic mechanisms? Arth Res
Therapy 15(2), 211
H., Jacques, T.S., Gunny, R., Wedderburn, L.R., Pilkington, C., Manzur, A.Y., (2013)
Limb girdle muscular dystrophy type 2B masquerading as inflammatory myopathy:
case report. Pediatr
Rheumatol Online J. 2013 May 3;11(1):19.
Sallum A., Varsani H.,
Holton, J.L., Marie, S. K. N., and Wedderburn, L. R. (2013) Morphometric analyses of
normal pediatric brachial biceps and quadriceps muscle tissue. Histology and Histopath 28:525-530
Martin, N., Krol, P., Smith,
S., Beard, L., Pilkington, C.A. Davidson J., Wedderburn L.R., and on behalf of
the Juvenile Dermatomyositis Research Group (JDRG). (2012) A comparison of children
with onset of Juvenile Dermatomyositis symptoms before or after their fifth
birthday in the UK and Ireland JDM Cohort study. Arthritis Care Res. 64(11) 1665-1672
Martin, N., Li, C. K., L. R. Wedderburn (2011).
Juvenile Dermatomyositis: new insights and new treatment strategies.
Therapeutic Advances in Musculoskeletal Disease.
Ye, Y., van Zyl, B., Varsani, H., Wedderburn, L. R., Ramana, A., Gillespie, K. M. (2012). Maternal michrochimerism in muscle biopsies from children with Juvenile Dermatomyositis.Rheumatology, 51(6) 987-991
Chinoy, H., Li, C., Platt H., Fertig, N., Varsani, H.,
Gunawardena, H., Betteridge, Z., Oddis, C.V. McHugh, N.J., Wedderburn L. R.,
Ollier, W.E.R., Cooper, R.G., for UK Adult Onset Myositis Immunogenetic
Collaboration & UK Juvenile Dermatomyositis Research Group (2012). Genetic
Association Study of NF-?B genes in UK Caucasian Adult and Juvenile Onset
Idiopathic Inflammatory Myopathy. Rheumatology. 51(5) 794-799
Davis, W. R., Halls, J. E.,
Offiah, A. C., Pilkington, C., Owens, C. M., and Rosendahl, K. (2011).
Assessment of active inflammation in juvenile dermatomyositis: a novel magnetic
resonance imaging-based scoring system. Rheumatology.
Martin, N., Krol, P., Smith, S., Murray, K., Pilkington, C. A., Davidson, J. E., Wedderburn, L. R (2011). A National Registry for Juvenile Dermatomyositis and other Paediatric Idiopathic Inflammatory Myopathies: 10 years experience (The Juvenile Dermatomyositis National (UK and Ireland) Cohort Biomarker Study and Repository for Idiopathic Inflammatory Myopathies). Rheumatology. 50(1):137-45.
Guseinova, D., Consolaro, A., Trail, L., Ferrari, C., Pistorio, A., Ruperto, N., Buoncompagni, A., Pilkington, C., Maillard, S., Oliveira, S. K., Sztajnbok, F., Cuttica, R., Corona, F., Katsicas, M. M., Russo, R., Ferriani, V., Burgos-Vargas, R., Solis-Vallejo, E., Bandeira, M., Baca, V., Saad-Magalhaes, C., Silva, C. A., Barcellona, R., Breda, L., Cimaz, R., Gallizzi, R., Garozzo, R., Martino, S., Meini, A., Stabile, A., Martini, A., Ravelli, A. (2011 Jan-Feb). Comparison of clinical features and drug therapies among European and Latin American patients with juvenile dermatomyositis. Clin Exp Rheumatol, 29(1): 117-24.
Huber, A. M., Giannini, E. H., Bowyer, S. L., Kim, S., Lang, B., Lindsley, C. B., Pachman, L. M., Pilkington, C., Reed, A. M., Rennebohm, R. M., Rider, L. G., Wallace, C. A., Feldman, B. M. (2010). Protocols for in initial treatment of moderately severe juvnile dermatomyositis: results of a Children's Arthritis and Rheumatology Research Alliance Consensus Conference. Arthritis Care Res, 62(2): 219-25.
Ravelli, A., Trail, L., Ferrari, C., Ruperto, N., Pistorio, A., Pilkington, C., Maillard, S., Oliveira, S. K., Sztajnbok, F., Cuttica, R., Beltramelli, M., Corona, F., Katsicas, M. M., Russo, R., Ferriani, V., Burgos-Vargas, R., Magni-Manzoni, S., Solis-Valleoji, E., Bandeira, M., Zulian, F., Baca, V., Cortis, E., Flacini, F., Alessio, M., Alpigiani, M. G., Gerloni, V., Saad-Magalhaes, C., Podda, R., Silva, C. A., Lepore, L., Felici, E., Rossi, F., Sala, E., Martini, A. (2010). A Long-term outcome and prognostic factors of juvenile dermatomyositis: A multinational, multicenter study of 490 patients. Arthritis Care Res, 62(1): 63-72.
Stringer, E., Bohnsack, J., Bowyer, S. L., Griffin, T. A., Huber, A. M., Lang, B., Lindsley, C. B., Ota, S., Pilkington, C., Reed, A. M., Scuccimarri, R., Feldman, B. M. (2010). Treatment approaches to juvenile dermatomyositis (JDM) across North America: The Childhood Arthritis and Rheumatology Research Alliance (CARRA) JDM Treatment Survey. J Rheumatol, 37(9): 1953-61.
Ruperto, N., Pistorio, A., Ravelli, A., Rider, L. G., Pilkington, C., Oliveira, S., Wulffraat, N., Espada, G., Garay, S., Cuttica, R., Hofer, M., Quartier, P., Melo-Gomes, J., Reed, A. M., Wierzbowska, M., Feldman, B. M., Harjacek, M., Huppertz, H. I., Nielsen, S., Flato, B., Lahdenne, P., Michels, H., Murray, K. J., Punaro, L., Rennebohm, R., Russo, R., Balogh, Z., Rooney, M., Pachman, L. M., Wallace, C., Hashkes, P., Lovell, D. J., Giannini, E. H., Gare, B. A., Martini, A. (2010, Nov). The Paediatric Rheumatology International Trials Organisation provisional criteria for the evaluation of response to therapy in juvenile dermatomyositis. A Paediatric Rheumatology International Trials Organisation (PRINTO); Pediatric Rheumatology Collaborative Study Group (PRCSG). Arthritis Care Res, 62(11): 1533-41.
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.
Lowry, C. A., & Pilkington, C. A. (2009). Juvenile dermatomyositis: extra-muscular manifestations and their management. Curr Opinion Rheumatology, 21(6): 575-580.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Wedderburn, L.R., McHugh, N. J., C
hinoy, 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.
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.
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
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.
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
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.
Pilkington, C.A. and Wedderburn, L. R. (2005). Paediatric Idiopathic Inflammatory Muscle Disease: Recognition and Management. Drugs 65 (10), 1355 – 1365.
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.
Wedderburn, L. R, (2004). Juvenile Dermatomyositis. Arthritis Today (Arthritis Research Campaign) 123, 10-12. Arthritis Research Campaign.
Wedderburn L. R. and Li, C. (2004). The pathogenesis of juvenile idiopathic inflammatory myopathies. Best Practice and Research Clinical Rheumatology 18(3), 345 – 358.
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
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.
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