Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes.
Pandemic influenza viruses often cause severe disease in middle-aged adults without preexisting comorbidities. The mechanism of illness associated with severe disease in this age group is not well understood. Here we find preexisting serum antibodies that cross-react with, but do not protect against, 2009 H1N1 influenza virus in middle-aged adults. Nonprotective antibody is associated with immune complex-mediated disease after infection. We detected high titers of serum antibody of low avidity for H1-2009 antigen, and low-avidity pulmonary immune complexes against the same protein, in severely ill individuals. Moreover, C4d deposition--a marker of complement activation mediated by immune complexes--was present in lung sections of fatal cases. Archived lung sections from middle-aged adults with confirmed fatal influenza 1957 H2N2 infection revealed a similar mechanism of illness. These observations provide a previously unknown biological mechanism for the unusual age distribution of severe cases during influenza pandemics.
Fundacion INFANT, Buenos Aires, Argentina.
Ana Clara
AC
Monsalvo
Juan P
JP
Batalle
M Florencia
MF
Lopez
Jens C
JC
Krause
Jennifer
J
Klemenc
Johanna Zea
JZ
Hernandez
Bernardo
B
Maskin
Jimena
J
Bugna
Carlos
C
Rubinstein
Leandro
L
Aguilar
Liliana
L
Dalurzo
Romina
R
Libster
Vilma
V
Savy
Elsa
E
Baumeister
Liliana
L
Aguilar
Graciela
G
Cabral
Julia
J
Font
Liliana
L
Solari
Kevin P
KP
Weller
Joyce
J
Johnson
Marcela
M
Echavarria
Kathryn M
KM
Edwards
James D
JD
Chappell
James E
JE
Crowe
John V
JV
Williams
Guillermina A
GA
Melendi
Fernando P
FP
Polack
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000914:Antibodies, Viral / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D003176:Complement C3 / Q000032:analysis; D003429:Cross Reactions / Q000276:immunology; D016207:Cytokines / Q000097:blood; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000821:virology; D016898:Interferon-alpha / Q000097:blood; D016899:Interferon-beta / Q000097:blood; D008168:Lung / Q000276:immunology / Q000473:pathology / Q000821:virology; D008875:Middle Aged; D055815:Young Adult
D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; D000956:Antigens, Viral; D003176:Complement C3; D016207:Cytokines; D016898:Interferon-alpha; D016899:Interferon-beta