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J Infect ; 63(4): 308-16, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21781987

RESUMO

AIM: Explore the role of viral factors and immune response in patients with severe pandemic pdmH1N1 illness without significant co-morbidity. MATERIALS: Seven patients with pdmH1N1 influenza, bilateral chest X-rays infiltrates, requiring mechanical ventilator support were consecutively recruited. Seven age- and gender-matched healthy individuals served as controls. RESULTS: Four patients were viremic, two with the mutant D222G/N pdmH1N1.Microarray analyses of peripheral blood leukocytes suggested a marked granulocytes activation, but no up-regulation of inflammatory cytokine mRNA. Patients with severe pdmH1NI had a marked systemic complement activation, and in contrast to the lack of cytokine mRNA up-regulation in blood leukocytes, plasma levels of a broad range of inflammatory mediators, including IP-10, and mediators involved in pulmonary remodelling were markedly elevated. Patients with mutant virus had particularly high IP-10 levels, and the most pronounced complement activation. CONCLUSIONS: In severe pdmH1N1, viremia was common and the D222G/N mutant was found in half of the viremic patients. Host immune response was characterized by strong activation of the innate immune system, including complement and granulocytes activation, increased serum levels of inflammation and pulmonary remodelling markers, possibly contributing to the observed tissue damage. However, few patients were included and further studies are needed to characterize the immune response in severe pdmH1N1 infection.


Assuntos
Imunidade Inata , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/patologia , Influenza Humana/virologia , Mutação de Sentido Incorreto , Neuraminidase/genética , Proteínas Virais/genética , Adulto , Substituição de Aminoácidos , Proteínas do Sistema Complemento , Citocinas/sangue , Citocinas/metabolismo , Granulócitos/imunologia , Humanos , Influenza Humana/complicações , Influenza Humana/imunologia , Dados de Sequência Molecular , Estudos Prospectivos , Radiografia Torácica , Respiração Artificial , Insuficiência Respiratória/epidemiologia , Insuficiência Respiratória/patologia , Análise de Sequência de DNA , Viremia/epidemiologia
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