Identifying and validating urine biomarkers in juvenile dermatomyositis (2017)

Melissa Morales, PhD
Binghamton University, State University of New York
Juvenile dermatomyositis (JDM) is an autoimmune disease affecting several tissues, including skeletal muscle and skin. Disease progression and response to treatment is highly variable between patients. This variability highlights the need to identify a panel of biomarkers that can be used to create personalized treatment regimens tailored for each patient. Studies have shown that urine biomarkers are just as reliable as those found in serum, and collecting urine samples from children is a less invasive method than obtaining blood specimens. Our aim is identify and validate new biomarkers in urine from JDM patients and test these biomarkers in patients who participated in the Rituximab in Myositis clinical trial.

Investigation of mechanisms that underlie differing phenotypes of JDM (2015)

Claire Deakin, PhD
University College, London, UK
Juvenile dermatomyositis (JDM) is a pediatric childhood-onset version of a severe autoimmune condition affecting skin and muscle. Although certain clinical features are common to both JDM and adult-onset dermatomyositis, the frequency of these features differs significantly, suggesting that the age of patients at the onset of disease affects disease processes. This project analyzes whether there is an association between age of disease onset and the role of genetic markers associated with the formation of calcium deposits, a serious complication associated with JDM but that is rare in adult-onset disease. It also investigates the biological role of these genetic markers in order to better understand the causes of calcium deposition. This research may lead to a better understanding of the risk of this complication, as well as identification of new drug targets to enable development of individualized treatments.

Predictive modeling of response to treatment in juvenile idiopathic inflammatory myopathies (2014)

Takayuki Kishi, MD, PhD
Tokyo Women’s Medical University Hospital, Tokyo, Japan
Few randomized controlled trials have been performed to accurately identify appropriate therapeutic options in patients with juvenile idiopathic inflammatory myopathies (JIIM). This research fellowship uses detailed data from a large cohort of JIIM patients (500 cases) to investigate medications received and predictors of clinical response to therapies. Three specific aims include: 1) to examine responses to myositis therapies, including use of medications in initial therapy and those used for treatment-refractory patients, 2) to test for a relationship between aggressiveness of therapies and subsequent disease outcomes, and 3) to compare various treatment regimens and examine differences in response rates and the impact on outcomes. These analyses should yield much new information on the therapies received, response rates, and predictors of responses to therapies in JIIM, as well as the impact of specific therapies and their timing on illness outcomes.

Effects of creatine supplementation in JDM (2013)

Brian Feldman, MD
Hospital for Sick Children, Toronto, CA
Juvenile dermatomyositis (JDM) is a rare disease characterized by inflammation of the muscle, which results in decreased oxygen to the muscle, deterioration of the muscle fibers, decreased muscle function, and persistent muscle weakness. Supplementation with pharmaceutical-grade creatine (CR) may be used as a treatment to ease muscle weakness in JDM patients. This project involves initial work to determine the feasibility of studying the effects of CR supplementation on muscle metabolism and function in JDM. Specifically, it uses new imaging techniques and exercise magnetic resonance spectroscopy (MRS) to look for changes in key products of metabolism (ATP, phosphocreatine, inorganic phosphate) responsible for healthy muscle function. Standard exercise testing is used to look for changes in muscle strength, power, and fatigue as a result of CR supplementation. Evidence supporting the use of CR in JDM, if successful, will provide the foundation for further research.

Phase II effectiveness trial in new onset JDM (2005)

Nicola Ruperto, MD
Insituto Gaslini, Genova, Italy
Researchers associated with the Pediatric Rheumatology International Trials Organization completed a study aimed at comparing three treatment strategies in children with recent onset juvenile dermatomyositis. The first group was treated with corticosteroids alone, the second with corticosteroids plus cyclosporine A, and the third with corticosteroids plus methotrexate. Results of this investigation indicate that combined treatment with prednisone and either cyclosporine or methotrexate was more effective than prednisone alone. The safety profile and steroid-sparing effect favored the combination of prednisone plus methotrexate.

Role of chimeric dendritic cells in the inflammatory process of JDM (2004)

Consuelo Lopez de Padilla, MD
Mayo Clinic, Rochester, MN
Dendritic cells (DC) are at the front lines of immune system defense, with distinct subsets being associated with different immune functions. Plasmacytoid DCs constitute a subset of cells that can be used specifically for the detection of viruses and may also play a role in the pathogenesis of systemic autoimmune disease. Little is known about the involvement of plasmacytoid DCs in the pathogenesis of juvenile DM, although these cells have been found in adult DM. In this study, researchers compared samples of muscle tissue from children with JDM to that of children with other disorders. They found that inflamed muscle tissue of JDM patients were densely infiltrated with plasmacytoid dendritic cells. These findings are consistent with the idea that plasmacytoid DCs are central to the initiation and perpetuation of muscle inflammation in JDM.

A multi-center study of the long-term outcome of juvenile idiopathic inflammatory myopathies (2004)

Angelo Ravelli, MD
Istituto Gaslini, Genova, Italy
This investigation evaluated the long-term prognosis of children and adolescents with juvenile dermatomyositis and sought predictors of poor outcome. Although a marked improvement in physical function when compared with earlier literature was documented, many patients had continued disease activity and cumulative damage at follow-up. A chronic course of disease activity was the strongest predictor of poor prognosis.

This investigation prompted researchers to develop a new tool, the Juvenile Dermatomyositis Multidimensional Assessment Report (JDMAR), which assesses the perception of patients and parents of the disease course and effectiveness of therapeutic interventions.

Juvenile myositis in Native Americans (2003)

James Jarvis, MD
University of Oklahoma, Norman, OK
This research, designed to examine the characteristics of rheumatic disease unique to Native American children, found that non-white children did not always fit the textbook descriptions for specific rheumatic diseases. For dermatomyositis, differences in disease expression between Native American and Caucasian children may cause confusion in diagnosis. For example, two of the six Native American children with juvenile myositis during the time of the study expressed the Jo-1 autoantibody, which is very rare in children. These patients frequently presented with joint swelling (synovitis) before the rash and muscle weakness became apparent. One patient developed severe weakness when treated with non-steroidal anti-inflammatory drugs before the myositis was recognized and steroid therapy was initiated. Researchers measured muscle enzyme blood levels on all Native American children presenting with signs and symptoms of synovitis, a practice that pediatricians would not routinely follow in Caucasian children.

Characterization of maternal microchimeric cells in males with JDM (2002)

Carol Artlett, BSc, PhD
Thomas Jefferson University, Philadelphia, PA
Microchimerism has been defined by the presence of a low number of circulating cells transferred from one individual to another. The transfer of microchimeric cells naturally takes place during pregnancy and occurs both ways between the mother and fetus. Microchimerism can also be a result of blood transfusions and organ transplants. These cells have been implicated in health and disease, for example in the pathogenesis of autoimmune diseases, including systemic sclerosis. In contrast, microchimeric cells were found to contribute to tissue repair. Much controversy exists around the role of microchimeric cells in the pathogenesis of certain diseases, and the presence of these cells in tissues may be a consequence rather than the cause of disease.

Childhood myositis heterogeneity study (2002)

Gulnara Mamyrova, MD, PhD
National Institute of Environmental Health Sciences, NIH
This fellowship enabled creation of a clinical database and follow-up data from a large population of patients with juvenile myositis. The registry has been called the Childhood Myositis Heterogeneity Study. Investigations completed during this fellowship included examination of a new myositis autoantibody associated with juvenile and adult dermatomyositis and investigation of immunogenetic risk and protective factors for juvenile myositis. It also examined whether parvovirus was a trigger for juvenile dermatomyositis.

Are lymphocytes activated at 10 years after diagnosis of JDM? (2002)

Lauren Pachman, MD
Children’s Memorial Hospital at Northwestern University, Chicago, IL
The initial symptoms of juvenile dermatomyositis (JDM) are a typical rash, often on the face, hands, and body, and muscle weakness that may be so severe that children cannot walk. This study showed that the genetic activation of circulating immune cells was associated with a child’s muscle damage rather than the changes in the skin related to inflammation. The data suggest that damage by the immune system to the child’s skin had a different pathway than the pathway by which the muscle was injured in JDM. This hypothesis was validated in later research.