A genomic storm in critically injured humans

Wenzhong Xiao, Michael N. Mindrinos, Junhee Seok, Joseph Cuschieri, Alex G. Cuenca, Hong Gao, Douglas L. Hayden, Laura Hennessy, Ernest E. Moore, Joseph P. Minei, Paul E. Bankey, Jeffrey L. Johnson, Jason Sperry, Avery B. Nathens, Timothy R. Billiar, Michael A. West, Bernard H. Brownstein, Philip H. Mason, Henry V. Baker, Celeste Finnerty & 76 others Marc G. Jeschke, M. Cecilia López, Matthew B. Klein, Richard L. Gamelli, Nicole S. Gibran, Brett Arnoldo, Weihong Xu, Yuping Zhang, Steven E. Calvano, Grace P. Mcdonald-Smith, David A. Schoenfeld, John D. Storey, J. Perren Cobb, H. Shaw Warren, Lyle L. Moldawer, David Herndon, Stephen F. Lowry, Ronald V. Maier, Ronald W. Davis, Ronald G. Tompkins, W. Xiao, M. Mindrinos, J. Seok, J. Cuschieri, R. Tompkins, R. Davis, R. Maier, L. Moldawer, L. Hennessy, E. Moore, J. Minei, P. Bankey, J. Johnson, J. Sperry, A. Nathens, T. Billiar, M. West, B. Brownstein, D. Herndon, H. Baker, C. Finnerty, M. Jeschke, M. Lopez, M. Klein, R. Gamelli, N. Gibran, B. Arnoldo, G. McDonald-Smith, D. Schoenfeld, J. Cobb, S. Warren, A. Cuenca, S. Lowry, S. Calvano, D. Hayden, P. Mason, H. Gao, J. Storey, Lily Altstein, Ulysses G J Balis, David G. Camp, K. De Asit, Brian G. Harbrecht, Shari E. Honari, Bruce A. McKinley, Carol L. Miller-Graziano, Frederick A. Moore, Grant E. O'Keefe, Laurence G. Rahme, Daniel G. Remick, Michael B. Shapiro, Richard D. Smith, Robert Tibshirani, Mehmet Toner, Bram Wispelwey, Wing H. Wong

Research output: Contribution to journalArticle

525 Citations (Scopus)

Abstract

Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and burn injury, as well as in healthy subjects receiving low-dose bacterial endotoxin, and show that these severe stresses produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected "genomic storm." In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. The similarities in gene expression patterns between different injuries reveal an apparently fundamental human response to severe inflammatory stress, with genomic signatures that are surprisingly far more common than different. Based on these transcriptional data, we propose a new paradigm for the human immunological response to severe injury.

Original languageEnglish (US)
Pages (from-to)2581-2590
Number of pages10
JournalJournal of Experimental Medicine
Volume208
Issue number13
DOIs
StatePublished - Dec 19 2011

Fingerprint

Wounds and Injuries
Leukocytes
Gene Expression
Adaptive Immunity
Cross Infection
Transcriptome
Endotoxins
Healthy Volunteers
Anti-Inflammatory Agents
Survival
Genes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Xiao, W., Mindrinos, M. N., Seok, J., Cuschieri, J., Cuenca, A. G., Gao, H., ... Wong, W. H. (2011). A genomic storm in critically injured humans. Journal of Experimental Medicine, 208(13), 2581-2590. https://doi.org/10.1084/jem.20111354

A genomic storm in critically injured humans. / Xiao, Wenzhong; Mindrinos, Michael N.; Seok, Junhee; Cuschieri, Joseph; Cuenca, Alex G.; Gao, Hong; Hayden, Douglas L.; Hennessy, Laura; Moore, Ernest E.; Minei, Joseph P.; Bankey, Paul E.; Johnson, Jeffrey L.; Sperry, Jason; Nathens, Avery B.; Billiar, Timothy R.; West, Michael A.; Brownstein, Bernard H.; Mason, Philip H.; Baker, Henry V.; Finnerty, Celeste; Jeschke, Marc G.; López, M. Cecilia; Klein, Matthew B.; Gamelli, Richard L.; Gibran, Nicole S.; Arnoldo, Brett; Xu, Weihong; Zhang, Yuping; Calvano, Steven E.; Mcdonald-Smith, Grace P.; Schoenfeld, David A.; Storey, John D.; Cobb, J. Perren; Warren, H. Shaw; Moldawer, Lyle L.; Herndon, David; Lowry, Stephen F.; Maier, Ronald V.; Davis, Ronald W.; Tompkins, Ronald G.; Xiao, W.; Mindrinos, M.; Seok, J.; Cuschieri, J.; Tompkins, R.; Davis, R.; Maier, R.; Moldawer, L.; Hennessy, L.; Moore, E.; Minei, J.; Bankey, P.; Johnson, J.; Sperry, J.; Nathens, A.; Billiar, T.; West, M.; Brownstein, B.; Herndon, D.; Baker, H.; Finnerty, C.; Jeschke, M.; Lopez, M.; Klein, M.; Gamelli, R.; Gibran, N.; Arnoldo, B.; McDonald-Smith, G.; Schoenfeld, D.; Cobb, J.; Warren, S.; Cuenca, A.; Lowry, S.; Calvano, S.; Hayden, D.; Mason, P.; Gao, H.; Storey, J.; Altstein, Lily; Balis, Ulysses G J; Camp, David G.; De Asit, K.; Harbrecht, Brian G.; Honari, Shari E.; McKinley, Bruce A.; Miller-Graziano, Carol L.; Moore, Frederick A.; O'Keefe, Grant E.; Rahme, Laurence G.; Remick, Daniel G.; Shapiro, Michael B.; Smith, Richard D.; Tibshirani, Robert; Toner, Mehmet; Wispelwey, Bram; Wong, Wing H.

In: Journal of Experimental Medicine, Vol. 208, No. 13, 19.12.2011, p. 2581-2590.

Research output: Contribution to journalArticle

Xiao, W, Mindrinos, MN, Seok, J, Cuschieri, J, Cuenca, AG, Gao, H, Hayden, DL, Hennessy, L, Moore, EE, Minei, JP, Bankey, PE, Johnson, JL, Sperry, J, Nathens, AB, Billiar, TR, West, MA, Brownstein, BH, Mason, PH, Baker, HV, Finnerty, C, Jeschke, MG, López, MC, Klein, MB, Gamelli, RL, Gibran, NS, Arnoldo, B, Xu, W, Zhang, Y, Calvano, SE, Mcdonald-Smith, GP, Schoenfeld, DA, Storey, JD, Cobb, JP, Warren, HS, Moldawer, LL, Herndon, D, Lowry, SF, Maier, RV, Davis, RW, Tompkins, RG, Xiao, W, Mindrinos, M, Seok, J, Cuschieri, J, Tompkins, R, Davis, R, Maier, R, Moldawer, L, Hennessy, L, Moore, E, Minei, J, Bankey, P, Johnson, J, Sperry, J, Nathens, A, Billiar, T, West, M, Brownstein, B, Herndon, D, Baker, H, Finnerty, C, Jeschke, M, Lopez, M, Klein, M, Gamelli, R, Gibran, N, Arnoldo, B, McDonald-Smith, G, Schoenfeld, D, Cobb, J, Warren, S, Cuenca, A, Lowry, S, Calvano, S, Hayden, D, Mason, P, Gao, H, Storey, J, Altstein, L, Balis, UGJ, Camp, DG, De Asit, K, Harbrecht, BG, Honari, SE, McKinley, BA, Miller-Graziano, CL, Moore, FA, O'Keefe, GE, Rahme, LG, Remick, DG, Shapiro, MB, Smith, RD, Tibshirani, R, Toner, M, Wispelwey, B & Wong, WH 2011, 'A genomic storm in critically injured humans', Journal of Experimental Medicine, vol. 208, no. 13, pp. 2581-2590. https://doi.org/10.1084/jem.20111354
Xiao W, Mindrinos MN, Seok J, Cuschieri J, Cuenca AG, Gao H et al. A genomic storm in critically injured humans. Journal of Experimental Medicine. 2011 Dec 19;208(13):2581-2590. https://doi.org/10.1084/jem.20111354
Xiao, Wenzhong ; Mindrinos, Michael N. ; Seok, Junhee ; Cuschieri, Joseph ; Cuenca, Alex G. ; Gao, Hong ; Hayden, Douglas L. ; Hennessy, Laura ; Moore, Ernest E. ; Minei, Joseph P. ; Bankey, Paul E. ; Johnson, Jeffrey L. ; Sperry, Jason ; Nathens, Avery B. ; Billiar, Timothy R. ; West, Michael A. ; Brownstein, Bernard H. ; Mason, Philip H. ; Baker, Henry V. ; Finnerty, Celeste ; Jeschke, Marc G. ; López, M. Cecilia ; Klein, Matthew B. ; Gamelli, Richard L. ; Gibran, Nicole S. ; Arnoldo, Brett ; Xu, Weihong ; Zhang, Yuping ; Calvano, Steven E. ; Mcdonald-Smith, Grace P. ; Schoenfeld, David A. ; Storey, John D. ; Cobb, J. Perren ; Warren, H. Shaw ; Moldawer, Lyle L. ; Herndon, David ; Lowry, Stephen F. ; Maier, Ronald V. ; Davis, Ronald W. ; Tompkins, Ronald G. ; Xiao, W. ; Mindrinos, M. ; Seok, J. ; Cuschieri, J. ; Tompkins, R. ; Davis, R. ; Maier, R. ; Moldawer, L. ; Hennessy, L. ; Moore, E. ; Minei, J. ; Bankey, P. ; Johnson, J. ; Sperry, J. ; Nathens, A. ; Billiar, T. ; West, M. ; Brownstein, B. ; Herndon, D. ; Baker, H. ; Finnerty, C. ; Jeschke, M. ; Lopez, M. ; Klein, M. ; Gamelli, R. ; Gibran, N. ; Arnoldo, B. ; McDonald-Smith, G. ; Schoenfeld, D. ; Cobb, J. ; Warren, S. ; Cuenca, A. ; Lowry, S. ; Calvano, S. ; Hayden, D. ; Mason, P. ; Gao, H. ; Storey, J. ; Altstein, Lily ; Balis, Ulysses G J ; Camp, David G. ; De Asit, K. ; Harbrecht, Brian G. ; Honari, Shari E. ; McKinley, Bruce A. ; Miller-Graziano, Carol L. ; Moore, Frederick A. ; O'Keefe, Grant E. ; Rahme, Laurence G. ; Remick, Daniel G. ; Shapiro, Michael B. ; Smith, Richard D. ; Tibshirani, Robert ; Toner, Mehmet ; Wispelwey, Bram ; Wong, Wing H. / A genomic storm in critically injured humans. In: Journal of Experimental Medicine. 2011 ; Vol. 208, No. 13. pp. 2581-2590.
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AU - Xiao, Wenzhong

AU - Mindrinos, Michael N.

AU - Seok, Junhee

AU - Cuschieri, Joseph

AU - Cuenca, Alex G.

AU - Gao, Hong

AU - Hayden, Douglas L.

AU - Hennessy, Laura

AU - Moore, Ernest E.

AU - Minei, Joseph P.

AU - Bankey, Paul E.

AU - Johnson, Jeffrey L.

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AU - Nathens, Avery B.

AU - Billiar, Timothy R.

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AU - Mason, Philip H.

AU - Baker, Henry V.

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AU - Jeschke, Marc G.

AU - López, M. Cecilia

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AU - Gamelli, Richard L.

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AU - Maier, Ronald V.

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AU - Finnerty, C.

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AU - Klein, M.

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AU - McDonald-Smith, G.

AU - Schoenfeld, D.

AU - Cobb, J.

AU - Warren, S.

AU - Cuenca, A.

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AU - Calvano, S.

AU - Hayden, D.

AU - Mason, P.

AU - Gao, H.

AU - Storey, J.

AU - Altstein, Lily

AU - Balis, Ulysses G J

AU - Camp, David G.

AU - De Asit, K.

AU - Harbrecht, Brian G.

AU - Honari, Shari E.

AU - McKinley, Bruce A.

AU - Miller-Graziano, Carol L.

AU - Moore, Frederick A.

AU - O'Keefe, Grant E.

AU - Rahme, Laurence G.

AU - Remick, Daniel G.

AU - Shapiro, Michael B.

AU - Smith, Richard D.

AU - Tibshirani, Robert

AU - Toner, Mehmet

AU - Wispelwey, Bram

AU - Wong, Wing H.

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AB - Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and burn injury, as well as in healthy subjects receiving low-dose bacterial endotoxin, and show that these severe stresses produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected "genomic storm." In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. The similarities in gene expression patterns between different injuries reveal an apparently fundamental human response to severe inflammatory stress, with genomic signatures that are surprisingly far more common than different. Based on these transcriptional data, we propose a new paradigm for the human immunological response to severe injury.

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