Severe pandemic 2009 H1N1 influenza disease due to pathogenic immune complexes

被引：205

作者：

Clara Monsalvo, Ana ^{[1
]}

Batalle, Juan P. ^{[1
]}

Florencia Lopez, M. ^{[1
]}

Krause, Jens C. ^{[2
]}

Klemenc, Jennifer ^{[2
]}

Zea Hernandez, Johanna ^{[1
,2
]}

Maskin, Bernardo ^{[3
]}

Bugna, Jimena ^{[1
]}

Rubinstein, Carlos ^{[4
]}

Aguilar, Leandro ^{[4
]}

Dalurzo, Liliana ^{[5
]}

Libster, Romina ^{[1
]}

Savy, Vilma ^{[6
,7
]}

Baumeister, Elsa ^{[6
,7
]}

Aguilar, Liliana ^{[3
]}

Cabral, Graciela ^{[3
]}

Font, Julia ^{[3
]}

Solari, Liliana ^{[3
]}

Weller, Kevin P. ^{[2
]}

Johnson, Joyce ^{[8
]}

Echavarria, Marcela ^{[9
]}

Edwards, Kathryn M. ^{[2
]}

Chappell, James D. ^{[8
]}

Crowe, James E., Jr. ^{[2
]}

Williams, John V. ^{[2
]}

Melendi, Guillermina A. ^{[1
,2
]}

Polack, Fernando P. ^{[1
,2
]}

机构：

[1] Fdn INFANT, Buenos Aires, DF, Argentina

[2] Vanderbilt Univ, Dept Pediat, Nashville, TN USA

[3] Hosp Nacl Prof Alejandro Posadas, Buenos Aires, DF, Argentina

[4] Hosp Dr Federico Abete, Buenos Aires, DF, Argentina

[5] Hosp Italiano Buenos Aires, Buenos Aires, DF, Argentina

[6] Adm Nacl Labs, Buenos Aires, DF, Argentina

[7] Inst Salud Dr Carlos G Malbran, Buenos Aires, DF, Argentina

[8] Vanderbilt Univ, Dept Pathol, Nashville, TN USA

[9] Ctr Educ Med & Invest Clin, Dept Microbiol, Buenos Aires, DF, Argentina

来源：

NATURE MEDICINE | 2011年 / 17卷 / 02期

基金：

美国国家卫生研究院;

关键词：

PNEUMONIA; INFECTION; RESPONSES; CHILDREN; VIRUSES; DEATH;

D O I：

10.1038/nm.2262

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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(1-10). 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.

引用

页码：195 / U225

页数：6

共 29 条

[1] Influenza-associated deaths among children in the United States, 2003-2004
Bhat, N
Wright, JG
Broder, KR
Murray, EL
Greenberg, ME
Glover, MJ
Likos, AM
Posey, DL
Klimov, A
Lindstrom, SE
Balish, A
Medina, MJ
Wallis, TR
Guarner, J
Paddock, CD
Shieh, WJ
Zaki, SR
Sejvar, JJ
Shay, DK
Harper, SA
Cox, NJ
Fukuda, K
Uyeki, TM
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2005, 353 (24) : 2559 - 2567
[2] Centers for Disease Control and Prevention (CDC), 2009, MMWR Morb Mortal Wkly Rep, V58, P521
[3] Severe Respiratory Disease Concurrent with the Circulation of H1N1 Influenza
Chowell, Gerardo
Bertozzi, Stefano M.
Colchero, M. Arantxa
Lopez-Gatell, Hugo
Alpuche-Aranda, Celia
Hernandez, Mauricio
Miller, Mark A.
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (07) : 674 - 679
[4] Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia
de Jong, Menno D.
Simmons, Cameron P.
Thanh, Tran Tan
Hien, Vo Minh
Smith, Gavin J. D.
Chau, Tran Nguyen Bich
Hoang, Dang Minh
Chau, Nguyen Van Vinh
Khanh, Truong Huu
Dong, Vo Cong
Qui, Phan Tu
Van Cam, Bach
Ha, Do Quang
Guan, Yi
Peiris, J. S. Malik
Chinh, Nguyen Tran
Hien, Tran Tinh
Farrar, Jeremy
[J]. NATURE MEDICINE, 2006, 12 (10) : 1203 - 1207
[5] Lack of antibody affinity maturation due to poor Toll-like receptor stimulation leads to enhanced respiratory syncytial virus disease
Florencia Delgado, Maria
Coviello, Silvina
Clara Monsalvo, A.
Melendi, Guillermina A.
Zea Hernandez, Johanna
Batalle, Juan P.
Diaz, Leandro
Trento, Alfonsina
Chang, Herng-Yu
Mitzner, Wayne
Ravetch, Jeffrey
Melero, Jose A.
Irusta, Pablo M.
Polack, Fernando P.
[J]. NATURE MEDICINE, 2009, 15 (01) : 34 - 41
[6] Cellular transcriptional profiling in influenza A virus-infected lung epithelial cells:: The role of the nonstructural NS1 protein in the evasion of the host innate defense and its potential contribution to pandemic influenza
Geiss, GK
Salvatore, M
Tumpey, TM
Carter, VS
Wang, XY
Basler, CF
Taubenberger, JK
Bumgarner, RE
Palese, P
Katze, MG
García-Sastre, A
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (16) : 10736 - 10741
[7] Pre-existing immunity against swine-origin H1N1 influenza viruses in the general human population
Greenbaum, Jason A.
Kotturi, Maya F.
Kim, Yohan
Oseroff, Carla
Vaughan, Kerrie
Salimi, Nima
Vita, Randi
Ponomarenko, Julia
Scheuermann, Richard H.
Sette, Alessandro
Peters, Bjoern
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (48) : 20365 - 20370
[8] INTERFERON-PRODUCTION IN CHILDREN WITH RESPIRATORY SYNCYTIAL, INFLUENZA, AND PARA-INFLUENZA VIRUS-INFECTIONS
HALL, CB
DOUGLAS, RG
SIMONS, RL
GEIMAN, JM
[J]. JOURNAL OF PEDIATRICS, 1978, 93 (01) : 28 - 32
[9] Cross-Reactive Antibody Responses to the 2009 Pandemic H1N1 Influenza Virus.
Hancock, Kathy
Veguilla, Vic
Lu, Xiuhua
Zhong, Weimin
Butler, Ebonee N.
Sun, Hong
Liu, Feng
Dong, Libo
DeVos, Joshua R.
Gargiullo, Paul M.
Brammer, T. Lynnette
Cox, Nancy J.
Tumpey, Terrence M.
Katz, Jacqueline M.
[J]. NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (20) : 1945 - 1952
[10] In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses
Itoh, Yasushi
Shinya, Kyoko
Kiso, Maki
Watanabe, Tokiko
Sakoda, Yoshihiro
Hatta, Masato
Muramoto, Yukiko
Tamura, Daisuke
Sakai-Tagawa, Yuko
Noda, Takeshi
Sakabe, Saori
Imai, Masaki
Hatta, Yasuko
Watanabe, Shinji
Li, Chengjun
Yamada, Shinya
Fujii, Ken
Murakami, Shin
Imai, Hirotaka
Kakugawa, Satoshi
Ito, Mutsumi
Takano, Ryo
Iwatsuki-Horimoto, Kiyoko
Shimojima, Masayuki
Horimoto, Taisuke
Goto, Hideo
Takahashi, Kei
Makino, Akiko
Ishigaki, Hirohito
Nakayama, Misako
Okamatsu, Masatoshi
Takahashi, Kazuo
Warshauer, David
Shult, Peter A.
Saito, Reiko
Suzuki, Hiroshi
Furuta, Yousuke
Yamashita, Makoto
Mitamura, Keiko
Nakano, Kunio
Nakamura, Morio
Brockman-Schneider, Rebecca
Mitamura, Hiroshi
Yamazaki, Masahiko
Sugaya, Norio
Suresh, M.
Ozawa, Makoto
Neumann, Gabriele
Gern, James
Kida, Hiroshi
[J]. NATURE, 2009, 460 (7258) : 1021 - U110

← 1 2 3 →