Gene-Expression Patterns Reveal Underlying Biological Processes in Kawasaki Disease
Popper, Stephen J
Kanegaye, John T
Brown, Patrick O
Burns, Jane C.
Relman, David A
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CitationPopper, Stephen J., Chisato Shimizu, Hiroko Shike, John T. Kanegaye, Jane W. Newburger, Robert P. Sundel, Patrick O. Brown, Jane C. Burns, and David A. Relman. 2007. Gene-expression patterns reveal underlying biological processes in Kawasaki disease. Genome Biology 8(12): R261.
AbstractBackground: Kawasaki disease (KD) is an acute self-limited vasculitis and the leading cause of
acquired heart disease in children in developed countries. No etiologic agent(s) has been identified, and the processes that mediate formation of coronary artery aneurysms and abatement of fever following treatment with intravenous immunoglobulin (IVIG) remain poorly understood. Results: In an initial survey, we used DNA microarrays to examine patterns of gene expression in peripheral whole blood from 20 children with KD; each was sampled during the acute, subacute, and convalescent phases of the illness. Acute KD was characterized by increased relative abundance of gene transcripts associated with innate immune and proinflammatory responses and decreased abundance of transcripts associated with natural killer cells and \(CD8^+\) lymphocytes. There was significant temporal variation in transcript levels during the acute disease phase and stabilization thereafter. We confirmed these temporal patterns in a second cohort of 64 patients, and identified additional inter-individual differences in transcript abundance. Notably, higher levels of transcripts of the gene for carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) were associated with an increased percentage of unsegmented neutrophils, fewer days of illness, higher levels of C-reactive protein, and subsequent non-response to IVIG; this last association was confirmed by quantitative reverse transcription PCR in a third cohort of 33 patients, and was independent of day of illness. Conclusion: Acute KD is characterized by dynamic and variable gene-expression programs that highlight the importance of neutrophil activation state and apoptosis in KD pathogenesis. Our findings also support the feasibility of extracting biomarkers associated with clinical prognosis from gene-expression profiles of individuals with systemic inflammatory illnesses.
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