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- Title
Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection.
- 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
- Abstract
<bold>Introduction: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusions: </bold>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.
- Publication
Critical Care, 2014, Vol 18, Issue 2, pR127
- ISSN
1364-8535
- Publication type
journal article
- DOI
10.1186/cc13934