Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

A.C MOSALVO; J. P BATALLE ; M.F LOPEZ; J.C. KRAUSE; J. KLEMENC; J.Z. HERNANDEZ; B. MASKIN; J. BUGNA; C. RUBINSTEIN; L.AGUILAR; L. DALURZO; R. LIBSTER; V.SAVY; E.BAUMEISTER; L.AGUILAR; G.CABRAL; J.FONT; L. SOLARI; K.P WELLER; J. JHONSON; M. ECHAVARRÍA; K.M. EDWARDS; J.D. CHAPPELL; J.E. CROWE; J.V. WILLIAMS; G.A. MELENDI; F.POLLACK

NATURE MEDICINE.

NATURE PUBLISHING GROUP

Año: 2011 p. 195 - 199

1078-8956

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