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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
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.
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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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