Lauren
M. Pachman, MD
Professor,
Department of Pediatrics,
Feinberg School of Medicine
Head, Division Immunology/Rheumatology,
Children's Memorial Medical Center
To Contact Dr. Pachman:
phone: 773-880-4303
e-mail: pachman@northwestern.edu
Dr. Pachman's website
Research Interests
Dr. Pachman’s investigation of Juvenile Dermatomyositis (JDM), a systemic
vasculopathy of unknown etiology, employs epidemiology (genetic and classical)
to characterize the genetic factors that govern disease susceptibility and
pathophysiology. Her lab has identified a genetic marker present in 85% of
all JDM, irrespective of race, the Class II antigen, DQA1*0501, as well as
the association of the TNF?-308 promoter A polymorphism with a prolonged disease
course requiring ? 36 month of immunosuppressive therapy. Micro array studies
document that 47% of the dysregulated genes specific to JDM are similar to
an anti-viral immune model, compared with a necrotizing pediatric myopathy
and to normal control muscle that do not express these genes (J Immunol, in
press, 2002). Intensive investigation will now focus on both the presumed
antigenic trigger and the contribution of the untreated patient (DQA1*0501?
chimerism in males? Duration of untreated disease prior to therapy?) to gene
expression seen in disease that is responsive to treatment compared with the
profiles of JDM children that are non-responsive to therapy. Resources for
further studies, obtained with consent for genetic research, include diagnostic
muscle biopsies stored at –80OC, sequential sera, peripheral blood lymphocytes
(some as isolated CD4/CD8 cells), and lymphocyte culture supernatant fluid.
Gene expression is confirmed by qRT-PCR, immunohistochemistry, and, where
appropriate ELISA and western blot. Laboratory data can be keyed to a longitudinal
coded patient derived database covering 20 years, which includes over 200
children with definite JDM. This information will help expand Dr. Pachman’s
laboratory’s understanding of the association of genotype with phenotypic
features of this often devastating disease, and may lead to more specific
and successful interventions.