tetano
Editor, Senior Moderator
Crit Care. 2014 Jun 20;18(3):R127. [Epub ahead of print]
Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection.
Herrera-Ramos E, L?pez-Rodr?guez M, Ru?z-Hern?ndez JJ, Horcajada JP, Border?as L, Lerma E, Blanquer J, P?rez-Gonz?lez MC, Garc?a-Laorden MI, Florido Y, Mas-Bosch V, Montero M, Ferrer JM, Sorl? L, Vilaplana C, Rajas O, Briones M, Aspa J, L?pez-Granados E, Sol?-Viol?n J, Rodr?guez de Castro F, Rodr?guez-Gallego C.
Abstract
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 1A0 were associated with need for mechanical ventilation, acute respiratory failure and acute respiratory distress syndrome. The SFTPA2 haplotype 1A1 was a protective variant. Kaplan-Meier analysis and Cox Regression also showed that diplotypes not containing the 1A1 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 1A0 (P = 0.0004) were associated, in a dose-dependent fashion, with lower PaO2/FiO2 ratio, whereas haplotype 1A1 was associated with a higher PaO2/FiO2 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 (1A1) SP-A2 for future IAV pandemics.
PMID:
24950659
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24950659
Surfactant protein A genetic variants associate with severe respiratory insufficiency in pandemic influenza A virus infection.
Herrera-Ramos E, L?pez-Rodr?guez M, Ru?z-Hern?ndez JJ, Horcajada JP, Border?as L, Lerma E, Blanquer J, P?rez-Gonz?lez MC, Garc?a-Laorden MI, Florido Y, Mas-Bosch V, Montero M, Ferrer JM, Sorl? L, Vilaplana C, Rajas O, Briones M, Aspa J, L?pez-Granados E, Sol?-Viol?n J, Rodr?guez de Castro F, Rodr?guez-Gallego C.
Abstract
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 1A0 were associated with need for mechanical ventilation, acute respiratory failure and acute respiratory distress syndrome. The SFTPA2 haplotype 1A1 was a protective variant. Kaplan-Meier analysis and Cox Regression also showed that diplotypes not containing the 1A1 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 1A0 (P = 0.0004) were associated, in a dose-dependent fashion, with lower PaO2/FiO2 ratio, whereas haplotype 1A1 was associated with a higher PaO2/FiO2 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 (1A1) SP-A2 for future IAV pandemics.
PMID:
24950659
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24950659