Author: Herrera-Ramos, EstefanÃa; López-RodrÃguez, Marta; RuÃz-Hernández, José Juan; Horcajada, Juan Pablo; BorderÃas, Luis; Lerma, Elisabeth; Blanquer, José; Pérez-González, MarÃa Carmen; GarcÃa-Laorden, MarÃa Isabel; Florido, Yanira; Mas-Bosch, Virginia; Montero, Milagro; Ferrer, José MarÃa; SorlÃ, Luisa; Vilaplana, Carlos; Rajas, Olga; Briones, Marisa; Aspa, Javier; López-Granados, Eduardo; Solé-Violán, Jordi; de Castro, Felipe RodrÃguez; RodrÃguez-Gallego, Carlos
Title: Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection Cord-id: w11azztq Document date: 2014_6_20
ID: w11azztq
Snippet: 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. METHOD
Document: 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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