Lauren Pachman, MD

Professor of Pediatrics
Feinberg School of Medicine

Head, Division of Pediatric Rheumatology
Children's Memorial Research Center

Research Interests:
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: Data bases: Northwestern/CMH based: sequential protocol driven clinical and diagnostic laboratory testing and family history of autoimmune disease from over 400 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 Laboratory data/resources: For the NU/CMH data base, the research laboratory has, with appropriate informed consent, diagnostic muscle biopsies, sequential samples of DNA, RNA, and peripheral blood mononuclear cells and their cultured supernatant fluid, which are keyed to the child’s coded ID number and prospectively obtained disease activity scores.

Specific Projects:

• Characterization of the IFN-α/β induced response in children with JDM with respect to disease evolution, epigenetics, and immunoregulation (in collaboration with Bento Soares, PhD).

• 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. (in collaboration with Y-W Chen, PhD)
• Characterization of pathological calcifications in children with JDM: This study identifies the composition of non-collagenous bone matrix proteins in pathological calcifications as well as the physical structure as determined by micro CT, FTIR, etc. (In collaboration with A. Boskey, PhD). The impact of the inflammatory response and changes in vascular function on the process of calcification will also be investigated (in collaboration with J. Cook-Mills, PhD).
• 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 for example, dysregulation of circulating lymphocyte phenotypes, and quality of life at 36 months or more after diagnosis of JDM.

Selected Publications:
Chen, Y. W., Shi, R., Geraci, N., Shrestha, S., Gordish-Dressman, H. and Pachman, L. M. (2008). Duration of chronic inflammation alters gene expression in muscle from untreated girls with juvenile dermatomyositis. BMC Immunol 9, 43.

Zankl, A., Pachman, L., Poznanski, A., Bonafe, L., Wang, F., Shusterman, Y., Fishman, D. A. and Superti-Furga, A. (2007). Torg syndrome is caused by inactivating mutations in MMP2 and is allelic to NAO and Winchester syndrome. J Bone Miner Res 22, 329-33.

Pachman, L. M., Abbott, K., Sinacore, J. M., Amoruso, L., Dyer, A., Lipton, R., Ilowite, N., Hom, C., Cawkwell, G., White, A. et al. (2006). Duration of illness is an important variable for untreated children with juvenile dermatomyositis. J Pediatr 148, 247-53.

Tezak, Z., Hoffman, E. P., Lutz, J. L., Fedczyna, T. O., Stephan, D., Bremer, E. G., Krasnoselska-Riz, I., Kumar, A. and Pachman, L. M. (2002). Gene expression profiling in DQA1*0501+ children with untreated dermatomyositis: a novel model of pathogenesis. J Immunol 168, 4154-63.

Pachman, L. M., Fedczyna, T. O., Lechman, T. S. and Lutz, J. (2001). Juvenile dermatomyositis: the association of the TNF alpha-308A allele and disease chronicity. Curr Rheumatol Rep 3, 379-86.