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Am J Respir Crit Care Med. 2014 Mar 19. [Epub ahead of print]
Low titers of serum antibodies inhibiting hemagglutination predict fatal fulminant influenza A(H1N1) 2009 infection.
Guihot A1, Luyt CE, Parrot A, Rousset D, Cavaillon JM, Boutolleau D, Fitting C, Pajanirassa P, Mallet A, Fartoukh M, Agut H, Musset L, Zoorob R, Kirilovsky A, Combadi?re B, Van der Werf S, Autran B, Carcelain G; the FluBAL study group.
Author information
Abstract
Rationale: The biology of fatal pandemic influenza infection remains undefined. Methods: This multicenter study included 34 unvaccinated patients with very severe or fatal confirmed influenza A(H1N1) infections. It analyzed plasma A(H1N1) 2009 RT-PCR, hemagglutinin 222G viral mutation, and humoral and cellular immune responses to the virus, assessed in hemagglutination inhibition (HI), microneutralization, ELISA, lymphoproliferative, ELISpot IFN-, and cytokine/chemokine assays. Measurements and Main Results: The patients' median age was 34 years. Influenza A(H1N1) 2009 viremia was detected in 4/34 cases, and a 222G hemagglutinin mutation in 7/17 cases, all of them with SOFA≥8. HI antibodies were detectable in 19/26 survivors and undetectable in all 6 fatal fulminant cases. ELISA and microneutralization titers were concordant. B-cell immunophenotyping and plasma levels of immunoglobulin classes did not differ between patients who survived and died. After immune complex dissociation, influenza ELISA serology became strongly positive in the bronchoalveolar lavage of the 2 fatal cases tested. H1N1-specific T-cell responses in lymphoproliferative and IFN- assays were weak in survivors' peripheral blood, and lymphoproliferative assays were negative in the 3 fatal cases tested. Plasma levels of IL-6 and IL-10 were high in fatal cases and correlated with severity. Finally, a negative HI serology 4 days after the onset of influenza symptoms predicted death from fulminant influenza (p=0.04). Conclusions: Early negative A(H1N1) 2009 HI serology can predict death from influenza. This negative serology in fatal cases in young adults reflects the trapping of anti-H1N1 antibodies in immune complexes in the lungs, associated with poor specific helper T-cell response.
PMID:
24646009
[PubMed - as supplied by publisher]
Low titers of serum antibodies inhibiting hemagglutination predict fatal fulminant influenza A(H1N1) 2009 infection.
Guihot A1, Luyt CE, Parrot A, Rousset D, Cavaillon JM, Boutolleau D, Fitting C, Pajanirassa P, Mallet A, Fartoukh M, Agut H, Musset L, Zoorob R, Kirilovsky A, Combadi?re B, Van der Werf S, Autran B, Carcelain G; the FluBAL study group.
Author information
Abstract
Rationale: The biology of fatal pandemic influenza infection remains undefined. Methods: This multicenter study included 34 unvaccinated patients with very severe or fatal confirmed influenza A(H1N1) infections. It analyzed plasma A(H1N1) 2009 RT-PCR, hemagglutinin 222G viral mutation, and humoral and cellular immune responses to the virus, assessed in hemagglutination inhibition (HI), microneutralization, ELISA, lymphoproliferative, ELISpot IFN-, and cytokine/chemokine assays. Measurements and Main Results: The patients' median age was 34 years. Influenza A(H1N1) 2009 viremia was detected in 4/34 cases, and a 222G hemagglutinin mutation in 7/17 cases, all of them with SOFA≥8. HI antibodies were detectable in 19/26 survivors and undetectable in all 6 fatal fulminant cases. ELISA and microneutralization titers were concordant. B-cell immunophenotyping and plasma levels of immunoglobulin classes did not differ between patients who survived and died. After immune complex dissociation, influenza ELISA serology became strongly positive in the bronchoalveolar lavage of the 2 fatal cases tested. H1N1-specific T-cell responses in lymphoproliferative and IFN- assays were weak in survivors' peripheral blood, and lymphoproliferative assays were negative in the 3 fatal cases tested. Plasma levels of IL-6 and IL-10 were high in fatal cases and correlated with severity. Finally, a negative HI serology 4 days after the onset of influenza symptoms predicted death from fulminant influenza (p=0.04). Conclusions: Early negative A(H1N1) 2009 HI serology can predict death from influenza. This negative serology in fatal cases in young adults reflects the trapping of anti-H1N1 antibodies in immune complexes in the lungs, associated with poor specific helper T-cell response.
PMID:
24646009
[PubMed - as supplied by publisher]
