Search

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.

Most individuals infected with the 2009 pandemic H1N1 influenza A virus (IAV) (H1N1pdm) experienced uncomplicated flu. However, in a small subset of patients the infection rapidly progressed to primary viral pneumonia (PVP) and a minority of them developed ARDS. Inherited and acquired variability in host immune responses may influence susceptibility and outcome of IAV infection. However, the molecular nature of such human factors remains largely elusive.

Genetic variability of the pulmonary surfactant proteins A and D may affect clearance of microorganisms and the extent of the inflammatory response. The genes of these collectins (SFTPA1, SFTPA2 and SFTPD) are located in a cluster at 10q21-24, near to the gene coding for mannose-binding lectin (MBL2), another collectin involved in innate immunity. The aim of this study was to evaluate the association of variability at SFTPA1, SFTPA2 and SFTPD with susceptibility to and severity of community-acquired pneumonia (CAP). Another objective was to evaluate the existence of linkage disequilibrium among SFTPA1, SFTPA2, SFTPD and MBL2.

The role of genetic variability in the susceptibility and outcome of influenza virus infection (IVI) remains largely unknown. We have previously demonstrated that variants at SFTPA2 influence the severity of H1N1pdm infection. We have now studied genetic variants at different genes, some of them previously associated with infections by influenza and/or other viruses. The purpose of this study was to analyze the role of genetic variants in the susceptibility and outcome of IVI.