Lauren M. Pachman, MD. Translational Research: Immunobiology and Immunotherapy of Juvenile Dermatomyositis
Overview: The current focus of this research team is the pathophysiology of Juvenile Dermatomyositis (JDM) the most common of the pediatric inflammatory myopathies, in which small blood vessels are attacked by the immune system. Little is known about the environmental and genetic risk factors associated with the development of the classic clinical symptoms of rash and often profound weakness. There is less information about the physical outcome of this chronic and sometimes fatal illness—including one of the most troubling complications, pathological calcifications—which are a major contributor to morbidity. A specific goal of this laboratory is to identify the most effective route/dose of the most commonly used drug for JDM, prednisone, and to develop targeted, effective interventions. To accomplish these specific aims, the following resources have been amassed, after obtaining informed consent:
Regional: sequential protocol based clinical and diagnostic laboratory testing and family history of autoimmune disease from over 250 children with JDM or other inflammatory myopathies, spanning over 25 years.
National: Structured interview and limited laboratory data at diagnosis and three year follow-up from 323 children with JDM and their families
Specific Research Projects:
Laboratory data/resources: For the regional data base, the research laboratory has sequential samples of DNA, RNA, and peripheral blood mononuclear cells and their supernatant fluid, which are keyed to the child’s coded ID number.
- Characterization of the IFN-α/β induced response in children with JDM before and after therapy. The purpose of this study is to determine the association of MXA gene expression in peripheral blood with clinical evidence of disease activity and cytokine expression. (K. O’Connor, PhD et al.)
- Gene expression profiles in muscle biopsy material from untreated children with JDM compared with other inflammatory myopathies. The purpose of this study is to identify the impact of specific variables on gene expression profiles: gender, age, duration of untreated disease, the presence of calcifications, etc, as well as to identify functional gene clusters that may be associated with the evolving pathophysiology of the inflammatory response. (LM Pachman, K. O’Connor, Yi-Wen Chen—DC Children’s)
- Characterization of pathological calcifications in children with JDM: This study identifies non-collagenous bone matrix proteins in pathological calcifications as well as the physical structure as determined by micro CT and x-ray diffraction (laboratory of S. Stock, PhD, nanotechnology). The impact of the inflammatory response and changes in vascular function on the process of calcification will also be investigated. (C. Chuu, A. Veiss, S. Stock, L.M. Pachman).
- The Pharmacokinetics of Prednisolone in Children with JDM: The purpose of this study is to determine the impact of vasculitis on the bioavailability of prednisolone as measured over an 8 hour time course. (K. Rouster-Stevens, C. Chuu).
- Outcomes of JDM: This study will describe the association of family history of autoimmune disease as well as various genetic markers (e.g.TNFα-308 A allele, DQA1*0501) with the physical findings, evidence of immune activation (dysregulation of lymphocyte phenotypes) and quality of life at 36 months or more after diagnosis of JDM. One cohort of patients will have fasting bloods assessed for levels of glucose, insulin and lipids. (Epidemiology team).
The research team is composed of two interlocking arms, Epidemiology and Immunobiology.
Patricia Meledy-Ray, MPH, Data management
Roopa Seshadri, Ph.D, Biostatistics (CMH Health Research)
Xiao-bin Wang, MD, MPH, Genetic epidemiology (CMH Health Research)
M. Klein-Gitelman, MD, MPH, Health economics (Immunology/Rheumatology)
James Sinacore, PhD, Loyola University, Biostatistical analysis
Ajith M. Joseph, PhD
Sheela Shrestha, MS
Maria Amoruso, MS
Nicholas Geraci, MS
Gabrielle Morgan, MA
Annette Urganus, BS