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 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.