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Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection
INTRODUCTION: Inherited variability in host immune responses influences susceptibility and outcome of Influenza A virus (IAV) infection, but these factors remain largely unknown. Components of the innate immune response may be crucial in the first days of the infection. The collectins surfactant pro...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229788/ https://www.ncbi.nlm.nih.gov/pubmed/24950659 http://dx.doi.org/10.1186/cc13934 |
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author | Herrera-Ramos, Estefanía López-Rodríguez, Marta Ruíz-Hernández, José Juan Horcajada, Juan Pablo Borderías, Luis Lerma, Elisabeth Blanquer, José Pérez-González, María Carmen García-Laorden, María Isabel Florido, Yanira Mas-Bosch, Virginia Montero, Milagro Ferrer, José María Sorlí, Luisa Vilaplana, Carlos Rajas, Olga Briones, Marisa Aspa, Javier López-Granados, Eduardo Solé-Violán, Jordi de Castro, Felipe Rodríguez Rodríguez-Gallego, Carlos |
author_facet | Herrera-Ramos, Estefanía López-Rodríguez, Marta Ruíz-Hernández, José Juan Horcajada, Juan Pablo Borderías, Luis Lerma, Elisabeth Blanquer, José Pérez-González, María Carmen García-Laorden, María Isabel Florido, Yanira Mas-Bosch, Virginia Montero, Milagro Ferrer, José María Sorlí, Luisa Vilaplana, Carlos Rajas, Olga Briones, Marisa Aspa, Javier López-Granados, Eduardo Solé-Violán, Jordi de Castro, Felipe Rodríguez Rodríguez-Gallego, Carlos |
author_sort | Herrera-Ramos, Estefanía |
collection | PubMed |
description | INTRODUCTION: Inherited variability in host immune responses influences susceptibility and outcome of Influenza A virus (IAV) infection, but these factors remain largely unknown. Components of the innate immune response may be crucial in the first days of the infection. The collectins surfactant protein (SP)-A1, -A2, and -D and mannose-binding lectin (MBL) neutralize IAV infectivity, although only SP-A2 can establish an efficient neutralization of poorly glycosylated pandemic IAV strains. METHODS: We studied the role of polymorphic variants at the genes of MBL (MBL2), SP-A1 (SFTPA1), SP-A2 (SFTPA2), and SP-D (SFTPD) in 93 patients with H1N1 pandemic 2009 (H1N1pdm) infection. RESULTS: Multivariate analysis showed that two frequent SFTPA2 missense alleles (rs1965708-C and rs1059046-A) and the SFTPA2 haplotype 1A(0) were associated with a need for mechanical ventilation, acute respiratory failure, and acute respiratory distress syndrome. The SFTPA2 haplotype 1A(1) was a protective variant. Kaplan-Meier analysis and Cox regression also showed that diplotypes not containing the 1A(1) haplotype were associated with a significantly shorter time to ICU admission in hospitalized patients. In addition, rs1965708-C (P = 0.0007), rs1059046-A (P = 0.0007), and haplotype 1A(0) (P = 0.0004) were associated, in a dose-dependent fashion, with lower PaO(2)/FiO(2) ratio, whereas haplotype 1A(1) was associated with a higher PaO(2)/FiO(2) ratio (P = 0.001). CONCLUSIONS: Our data suggest an effect of genetic variants of SFTPA2 on the severity of H1N1pdm infection and could pave the way for a potential treatment with haplotype-specific (1A(1)) SP-A2 for future IAV pandemics. |
format | Online Article Text |
id | pubmed-4229788 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-42297882014-11-14 Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection Herrera-Ramos, Estefanía López-Rodríguez, Marta Ruíz-Hernández, José Juan Horcajada, Juan Pablo Borderías, Luis Lerma, Elisabeth Blanquer, José Pérez-González, María Carmen García-Laorden, María Isabel Florido, Yanira Mas-Bosch, Virginia Montero, Milagro Ferrer, José María Sorlí, Luisa Vilaplana, Carlos Rajas, Olga Briones, Marisa Aspa, Javier López-Granados, Eduardo Solé-Violán, Jordi de Castro, Felipe Rodríguez Rodríguez-Gallego, Carlos Crit Care Research INTRODUCTION: Inherited variability in host immune responses influences susceptibility and outcome of Influenza A virus (IAV) infection, but these factors remain largely unknown. Components of the innate immune response may be crucial in the first days of the infection. The collectins surfactant protein (SP)-A1, -A2, and -D and mannose-binding lectin (MBL) neutralize IAV infectivity, although only SP-A2 can establish an efficient neutralization of poorly glycosylated pandemic IAV strains. METHODS: We studied the role of polymorphic variants at the genes of MBL (MBL2), SP-A1 (SFTPA1), SP-A2 (SFTPA2), and SP-D (SFTPD) in 93 patients with H1N1 pandemic 2009 (H1N1pdm) infection. RESULTS: Multivariate analysis showed that two frequent SFTPA2 missense alleles (rs1965708-C and rs1059046-A) and the SFTPA2 haplotype 1A(0) were associated with a need for mechanical ventilation, acute respiratory failure, and acute respiratory distress syndrome. The SFTPA2 haplotype 1A(1) was a protective variant. Kaplan-Meier analysis and Cox regression also showed that diplotypes not containing the 1A(1) haplotype were associated with a significantly shorter time to ICU admission in hospitalized patients. In addition, rs1965708-C (P = 0.0007), rs1059046-A (P = 0.0007), and haplotype 1A(0) (P = 0.0004) were associated, in a dose-dependent fashion, with lower PaO(2)/FiO(2) ratio, whereas haplotype 1A(1) was associated with a higher PaO(2)/FiO(2) ratio (P = 0.001). CONCLUSIONS: Our data suggest an effect of genetic variants of SFTPA2 on the severity of H1N1pdm infection and could pave the way for a potential treatment with haplotype-specific (1A(1)) SP-A2 for future IAV pandemics. BioMed Central 2014 2014-06-20 /pmc/articles/PMC4229788/ /pubmed/24950659 http://dx.doi.org/10.1186/cc13934 Text en Copyright © 2014 Herrera-Ramos et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Herrera-Ramos, Estefanía López-Rodríguez, Marta Ruíz-Hernández, José Juan Horcajada, Juan Pablo Borderías, Luis Lerma, Elisabeth Blanquer, José Pérez-González, María Carmen García-Laorden, María Isabel Florido, Yanira Mas-Bosch, Virginia Montero, Milagro Ferrer, José María Sorlí, Luisa Vilaplana, Carlos Rajas, Olga Briones, Marisa Aspa, Javier López-Granados, Eduardo Solé-Violán, Jordi de Castro, Felipe Rodríguez Rodríguez-Gallego, Carlos Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection |
title | Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection |
title_full | Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection |
title_fullStr | Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection |
title_full_unstemmed | Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection |
title_short | Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection |
title_sort | surfactant protein a genetic variants associate with severe respiratory insufficiency in pandemic influenza a virus infection |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229788/ https://www.ncbi.nlm.nih.gov/pubmed/24950659 http://dx.doi.org/10.1186/cc13934 |
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