Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection

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,...

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Published in:Critical care (London, England) England), 2014-06, Vol.18 (3), p.R127-R127
Main Authors: 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
Format: Article
Language:English
Subjects:
Acute respiratory distress syndrome
Adult
Analysis
Blood Pressure
Complications and side effects
Female
Genetic aspects
Haplotypes
Health aspects
Hospitalization
Humans
Immune response
Influenza A virus
Influenza A Virus, H1N1 Subtype
Influenza, Human - genetics
Influenza, Human - physiopathology
Male
Mutation, Missense
Patient outcomes
Polymorphism, Single Nucleotide
Prospective Studies
Pulmonary Surfactant-Associated Protein A - genetics
Respiratory insufficiency
Retrospective Studies
Risk factors
Severity of Illness Index
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Summary: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. 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. 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 PaO2/FiO2 ratio, whereas haplotype 1A(1) was associated with a higher PaO2/FiO2 ratio (P = 0.001). 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.
ISSN:1364-8535
1466-609X
DOI:10.1186/cc13934