Resumo

HOUGHTON-TRIVINO, Natalia et al. Comparison of the transcriptional profiles of patients with dengue fever and dengue hemorrhagic fever reveals differences in the immune response and clues in immunopathogenesis. Biomédica [online]. 2010, vol.30, n.4, pp.587-597. ISSN 0120-4157.

Introduction. Dengue infection demonstrates a wide spectrum of clinical manifestations from mild disease (dengue fever) to severe dengue hemorrhagic fever, but the immunopathogenic mechanisms involved in disease severity are not clear. Objective. Differentially expressed genes associated to immune response were indentified from peripheral blood mononuclear cells of Colombian children with dengue fever and dengue hemorrhagic fever. Materials and methods. Microarray analysis was used as a tool to establish and compare transcriptional profiles of peripheral blood mononuclear cells of six children in acute phase of dengue fever and dengue hemorrhagic fever. The commercial gene chip used was Affymnetrix GeneChip HG_U133_Plus_2. Results. Dengue hemorrhagic fever patients expressed interleukin 6, chemokines, complement proteins and pentraxin 3, along with the lymphocyte inhibitors lymphocyte-activation gene 3 and cathepsin L1. An interaction model for these genes showed tissue factor playing a central role in the network generated. In contrast, dengue fever patients expressed cytokines, complement and the leukotrienes inhibitors lactotransferrin, C1 inhibitor, and leukotriene-B (4-omega-hydroxylase 2). Conclusions. These results indicate that in dengue fever, cytokine and complement inhibitors are able to limit endothelial damage and prevent increases in vascular permeability, whereas dengue- hemorrhagic fever patients have immune cell dysfunction and unregulated complement and cytokine action. This leads to “hypercoagulation” and endothelial damage, thereby increasing disease severity. Verification of the pathogenic role of the identified molecules will contribute to understanding of dengue pathogenesis and lead to rational development of therapeutic drugs.

Palavras-chave : dengue; transcription, genetic; microarray analysis; dengue hemorrhagic fever; complement system proteins; cytokines.

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