RESUMEN
Introduction of a novel influenza virus into the human population leads to the occurrence of pandemic events, such as the one caused by pandemic influenza A (H1N1) 2009 virus. The severity of infections caused by this virus in young adults was greater than that observed in patients with seasonal influenza. Fatal cases have been associated with an abnormal innate, proinflammatory immune response. A critical role for natural killer cells during the initial responses to influenza infections has been suggested. In this study, we assessed the association of killer-cell immunoglobulin-like receptors (KIRs) with disease severity by comparing KIR gene content in patients with mild and severe pandemic influenza virus infections to a control group. We found that activator (KIR3DS1 and KIR2DS5) and inhibitory (KIR2DL5) genes, encoded in group B haplotypes containing the cB01, cB03 and tB01 motifs, are associated with severe pandemic influenza A (H1N1) 2009 infections. Better understanding of how genetic variability contributes to influenza virus pathogenesis may help to the development of immune intervention strategies aiming at controlling the severity of disease.
Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Gripe Humana/genética , Receptores KIR2DL5/genética , Receptores KIR3DS1/genética , Receptores KIR/genética , Adolescente , Adulto , Anciano , Secuencias de Aminoácidos , Niño , Preescolar , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Gripe Humana/epidemiología , Gripe Humana/patología , Masculino , México/epidemiología , Persona de Mediana Edad , Pandemias , Isoformas de Proteínas/genética , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND/AIMS: Killer cell immunoglobulin-like receptors (KIR) are involved in the activation/inhibition of NK cells through an interaction with HLA class I molecules on target cells. Our study aimed to evaluate the association between KIR gene polymorphisms and the response of patients with CHC to antiviral therapy. METHODS: We compared the frequency of KIR genes, as well as that of compound KIR/HLA-C genotypes, between groups of patients with CHC who presented a sustained virological response (n=66) and who were non-responders to a combination of pegylated or standard interferon and ribavirin (n=101). KIR and HLA-C genotyping were performed using commercial kits. RESULTS: We detected a greater frequency of the KIR2DL5 gene among non-responders to antiviral therapy compared with sustained virological responders (68.3 vs. 40.9%) (P<0.001). We used multiple logistic regression analysis to determine the association between therapy response and the presence of KIR2DL5, after a control for potentially confounding variables (genotype, alcohol, fibrosis, gender, age, ethnic background and route of HCV infection). The results confirmed the strong association between the presence of KIR2DL5 and the non-response to antiviral treatment (P=0.001). CONCLUSIONS: Host genetic factors may be associated with a non-response to antiviral therapy. KIR2DL5 is a candidate gene involved in immunomodulation associated with non-response to antiviral therapy.