Disease-associated pathophysiologic structures in pediatric rheumatic diseases show characteristics of scale-free networks seen in physiologic systems: implications for pathogenesis and treatment

<p>Abstract</p> <p>Background</p> <p>While standard reductionist approaches have provided some insights into specific gene polymorphisms and molecular pathways involved in disease pathogenesis, our understanding of complex traits such as atherosclerosis or type 2 diabetes remains incomplete. Gene expression profiling provides an unprecedented opportunity to understand complex human diseases by providing a global view of the multiple interactions across the genome that are likely to contribute to disease pathogenesis. Thus, the goal of gene expression profiling is not to generate lists of differentially expressed genes, but to identify the physiologic or pathogenic processes and structures represented in the expression profile.</p> <p>Methods</p> <p>RNA was separately extracted from peripheral blood neutrophils and mononuclear leukocytes, labeled, and hybridized to genome level microarrays to generate expression profiles of children with polyarticular juvenile idiopathic arthritis, juvenile dermatomyositis relative to childhood controls. Statistically significantly differentially expressed genes were identified from samples of each disease relative to controls. Functional network analysis identified interactions between products of these differentially expressed genes.</p> <p>Results</p> <p><it>In silico </it>models of both diseases demonstrated similar features with properties of scale-free networks previously described in physiologic systems. These networks were observable in both cells of the innate immune system (neutrophils) and cells of the adaptive immune system (peripheral blood mononuclear cells).</p> <p>Conclusion</p> <p>Genome-level transcriptional profiling from childhood onset rheumatic diseases suggested complex interactions in two arms of the immune system in both diseases. The disease associated networks showed scale-free network patterns similar to those reported in normal physiology. We postulate that these features have important implications for therapy as such networks are relatively resistant to perturbation.</p

Pregnancy outcome in idiopathic inflammatory myopathy

The aim of our study was to assess the prevalence and outcome of pregnancy in idiopathic inflammatory myopathy patients who became pregnant after the onset of the disease. Female idiopathic inflammatory myopathy patients (173) were included in our study. The patients' charts and clinical data were retrospectively analyzed. One hundred and four female idiopathic inflammatory myopathy patients had 186 pregnancies, but only nine of these patients (4 polymyositis-PM, 5 dermatomyositis-DM) became pregnant after the onset of the disease. Nine patients with pregnancies after the disease onset had 14 gravidities. Six pregnancies resulted in normal deliveries, two ended in prematurity, six ended in abortions (two induced abortions). Regarding the four patients (3 PM, 1 DM) with active disease at the time of pregnancy, two pregnancies ended in prematurity, four ended in spontaneous abortion and one healthy baby delivered. The other five patients (2 PM, 3 DM) with the disease in remission had uneventful pregnancies and healthy babies were delivered. Treatment was not required during pregnancy in case of two dermatomyositis patients with long lasting remission. New onset dermatomyositis developed in one patient in her pregnancy's third trimester. The mean weight of newborns in the active myositis cases was 2,193 (1,680-2,700) g; while in patients with remission was 3,167 (2,800-3,800) g. The active maternal disease in idiopathic inflammatory myopathy (IIM) might result intrauterin retardation and death. Disease activity in active and new-onset cases could be controlled by increasing the dose of corticosteroid