Defining immunological dysfunction in sepsis: A requisite tool for precision medicine

Jesús F. Bermejo-Martin; David Andaluz-Ojeda; Raquel Almansa; Francisco Gandía; Jose Ignacio Gómez-Herreras; Esther Gomez-Sanchez; María Heredia-Rodríguez; Jose Maria Eiros; David J. Kelvin; Eduardo Tamayo

doi:10.1016/j.jinf.2016.01.010

Defining immunological dysfunction in sepsis: A requisite tool for precision medicine

Jesús F. Bermejo-Martin, David Andaluz-Ojeda, Raquel Almansa, Francisco Gandía, Jose Ignacio Gómez-Herreras, Esther Gomez-Sanchez, María Heredia-Rodríguez, Jose Maria Eiros, David J. Kelvin, Eduardo Tamayo

Research output: Contribution to journal › Review article › peer-review

78 Citations (Scopus)

Abstract

Objectives: Immunological dysregulation is now recognised as a major pathogenic event in sepsis. Stimulation of immune response and immuno-modulation are emerging approaches for the treatment of this disease. Defining the underlying immunological alterations in sepsis is important for the design of future therapies with immuno-modulatory drugs. Methods: Clinical studies evaluating the immunological response in adult patients with Sepsis and published in PubMed were reviewed to identify features of immunological dysfunction. For this study we used key words related with innate and adaptive immunity. Results: Ten major features of immunological dysfunction (FID) were identified involving quantitative and qualitative alterations of [antigen presentation](FID1), [T and B lymphocytes] (FID2), [natural killer cells] (FID3), [relative increase in T regulatory cells] (FID4), [increased expression of PD-1 and PD-ligand1](FID5), [low levels of immunoglobulins](FID6), [low circulating counts of neutrophils and/or increased immature forms in non survivors](FID7), [hyper-cytokinemia] (FID8), [complement consumption] (FID9), [defective bacterial killing by neutrophil extracellular traps](FID10). Conclusions: This review article identified ten major features associated with immunosuppression and immunological dysregulation in sepsis. Assessment of these features could help in utilizing precision medicine for the treatment of sepsis with immuno-modulatory drugs.

Original language	English
Pages (from-to)	525-536
Number of pages	12
Journal	Journal of Infection
Volume	72
Issue number	5
DOIs	https://doi.org/10.1016/j.jinf.2016.01.010
Publication status	Published - May 1 2016
Externally published	Yes

Bibliographical note

Funding Information:
We thank Lucia Rico, Veronica Iglesias, and Alicia Ortega for their dedication to our research in immunity and sepsis throughout the years. We appreciate the help of Nikki Kelvin with language editing. We also thank the Intensive Care Unit and the Anaesthesiology Service for their continuous support of our work and the “ Instituto de Salud Carlos III ” and “ Consejería de Sanidad de Castilla y León ” for their financial support, grant numbers [ EMER 07/050 ], [ PI10/01362 ] and [ PI13/02110 ]. JFBM, RA contracts are supported by IECSCYL, Spain ; DAO, JIGH, EGS and MHR contracts are supported by SACYL, Spain ; JME and ET contracts are supported by the University of Valladolid, Spain . Supporter institutions had no involvement in any of the aspects needed for the elaboration of this manuscript.

Publisher Copyright:
© 2016 The British Infection Association.

ASJC Scopus Subject Areas

Microbiology (medical)
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jinf.2016.01.010

Cite this

Bermejo-Martin, J. F., Andaluz-Ojeda, D., Almansa, R., Gandía, F., Gómez-Herreras, J. I., Gomez-Sanchez, E., Heredia-Rodríguez, M., Eiros, J. M., Kelvin, D. J., & Tamayo, E. (2016). Defining immunological dysfunction in sepsis: A requisite tool for precision medicine. Journal of Infection, 72(5), 525-536. https://doi.org/10.1016/j.jinf.2016.01.010

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title = "Defining immunological dysfunction in sepsis: A requisite tool for precision medicine",

abstract = "Objectives: Immunological dysregulation is now recognised as a major pathogenic event in sepsis. Stimulation of immune response and immuno-modulation are emerging approaches for the treatment of this disease. Defining the underlying immunological alterations in sepsis is important for the design of future therapies with immuno-modulatory drugs. Methods: Clinical studies evaluating the immunological response in adult patients with Sepsis and published in PubMed were reviewed to identify features of immunological dysfunction. For this study we used key words related with innate and adaptive immunity. Results: Ten major features of immunological dysfunction (FID) were identified involving quantitative and qualitative alterations of [antigen presentation](FID1), [T and B lymphocytes] (FID2), [natural killer cells] (FID3), [relative increase in T regulatory cells] (FID4), [increased expression of PD-1 and PD-ligand1](FID5), [low levels of immunoglobulins](FID6), [low circulating counts of neutrophils and/or increased immature forms in non survivors](FID7), [hyper-cytokinemia] (FID8), [complement consumption] (FID9), [defective bacterial killing by neutrophil extracellular traps](FID10). Conclusions: This review article identified ten major features associated with immunosuppression and immunological dysregulation in sepsis. Assessment of these features could help in utilizing precision medicine for the treatment of sepsis with immuno-modulatory drugs.",

author = "Bermejo-Martin, {Jes{\'u}s F.} and David Andaluz-Ojeda and Raquel Almansa and Francisco Gand{\'i}a and G{\'o}mez-Herreras, {Jose Ignacio} and Esther Gomez-Sanchez and Mar{\'i}a Heredia-Rodr{\'i}guez and Eiros, {Jose Maria} and Kelvin, {David J.} and Eduardo Tamayo",

note = "Funding Information: We thank Lucia Rico, Veronica Iglesias, and Alicia Ortega for their dedication to our research in immunity and sepsis throughout the years. We appreciate the help of Nikki Kelvin with language editing. We also thank the Intensive Care Unit and the Anaesthesiology Service for their continuous support of our work and the “ Instituto de Salud Carlos III ” and “ Consejer{\'i}a de Sanidad de Castilla y Le{\'o}n ” for their financial support, grant numbers [ EMER 07/050 ], [ PI10/01362 ] and [ PI13/02110 ]. JFBM, RA contracts are supported by IECSCYL, Spain ; DAO, JIGH, EGS and MHR contracts are supported by SACYL, Spain ; JME and ET contracts are supported by the University of Valladolid, Spain . Supporter institutions had no involvement in any of the aspects needed for the elaboration of this manuscript. Publisher Copyright: {\textcopyright} 2016 The British Infection Association.",

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doi = "10.1016/j.jinf.2016.01.010",

language = "English",

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TY - JOUR

T1 - Defining immunological dysfunction in sepsis

T2 - A requisite tool for precision medicine

AU - Bermejo-Martin, Jesús F.

AU - Andaluz-Ojeda, David

AU - Almansa, Raquel

AU - Gandía, Francisco

AU - Gómez-Herreras, Jose Ignacio

AU - Gomez-Sanchez, Esther

AU - Heredia-Rodríguez, María

AU - Eiros, Jose Maria

AU - Kelvin, David J.

AU - Tamayo, Eduardo

N1 - Funding Information: We thank Lucia Rico, Veronica Iglesias, and Alicia Ortega for their dedication to our research in immunity and sepsis throughout the years. We appreciate the help of Nikki Kelvin with language editing. We also thank the Intensive Care Unit and the Anaesthesiology Service for their continuous support of our work and the “ Instituto de Salud Carlos III ” and “ Consejería de Sanidad de Castilla y León ” for their financial support, grant numbers [ EMER 07/050 ], [ PI10/01362 ] and [ PI13/02110 ]. JFBM, RA contracts are supported by IECSCYL, Spain ; DAO, JIGH, EGS and MHR contracts are supported by SACYL, Spain ; JME and ET contracts are supported by the University of Valladolid, Spain . Supporter institutions had no involvement in any of the aspects needed for the elaboration of this manuscript. Publisher Copyright: © 2016 The British Infection Association.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - Objectives: Immunological dysregulation is now recognised as a major pathogenic event in sepsis. Stimulation of immune response and immuno-modulation are emerging approaches for the treatment of this disease. Defining the underlying immunological alterations in sepsis is important for the design of future therapies with immuno-modulatory drugs. Methods: Clinical studies evaluating the immunological response in adult patients with Sepsis and published in PubMed were reviewed to identify features of immunological dysfunction. For this study we used key words related with innate and adaptive immunity. Results: Ten major features of immunological dysfunction (FID) were identified involving quantitative and qualitative alterations of [antigen presentation](FID1), [T and B lymphocytes] (FID2), [natural killer cells] (FID3), [relative increase in T regulatory cells] (FID4), [increased expression of PD-1 and PD-ligand1](FID5), [low levels of immunoglobulins](FID6), [low circulating counts of neutrophils and/or increased immature forms in non survivors](FID7), [hyper-cytokinemia] (FID8), [complement consumption] (FID9), [defective bacterial killing by neutrophil extracellular traps](FID10). Conclusions: This review article identified ten major features associated with immunosuppression and immunological dysregulation in sepsis. Assessment of these features could help in utilizing precision medicine for the treatment of sepsis with immuno-modulatory drugs.

AB - Objectives: Immunological dysregulation is now recognised as a major pathogenic event in sepsis. Stimulation of immune response and immuno-modulation are emerging approaches for the treatment of this disease. Defining the underlying immunological alterations in sepsis is important for the design of future therapies with immuno-modulatory drugs. Methods: Clinical studies evaluating the immunological response in adult patients with Sepsis and published in PubMed were reviewed to identify features of immunological dysfunction. For this study we used key words related with innate and adaptive immunity. Results: Ten major features of immunological dysfunction (FID) were identified involving quantitative and qualitative alterations of [antigen presentation](FID1), [T and B lymphocytes] (FID2), [natural killer cells] (FID3), [relative increase in T regulatory cells] (FID4), [increased expression of PD-1 and PD-ligand1](FID5), [low levels of immunoglobulins](FID6), [low circulating counts of neutrophils and/or increased immature forms in non survivors](FID7), [hyper-cytokinemia] (FID8), [complement consumption] (FID9), [defective bacterial killing by neutrophil extracellular traps](FID10). Conclusions: This review article identified ten major features associated with immunosuppression and immunological dysregulation in sepsis. Assessment of these features could help in utilizing precision medicine for the treatment of sepsis with immuno-modulatory drugs.

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Defining immunological dysfunction in sepsis: A requisite tool for precision medicine

Abstract

Bibliographical note

ASJC Scopus Subject Areas

UN SDGs

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