Deciphering heterogeneity of septic shock patients using immune functional assays: a proof of concept study
The complexity of sepsis pathophysiology hinders patient management and therapeutic decisions. In this proof-of-concept study we characterised the underlying host immune response alterations using a standardised immune functional assay (IFA) in order to stratify a sepsis population. In septic shock...
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| Veröffentlicht in: | Scientific reports 2020-09, Vol.10 (1), p.16136-16136, Article 16136 |
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| creator | Albert Vega, Chloé Oriol, Guy Bartolo, François Lopez, Jonathan Pachot, Alexandre Rimmelé, Thomas Venet, Fabienne Leray, Véronique Monneret, Guillaume Delwarde, Benjamin Brengel-Pesce, Karen Textoris, Julien Mallet, François Trouillet-Assant, Sophie |
| description | The complexity of sepsis pathophysiology hinders patient management and therapeutic decisions. In this proof-of-concept study we characterised the underlying host immune response alterations using a standardised immune functional assay (IFA) in order to stratify a sepsis population. In septic shock patients, ex vivo LPS and SEB stimulations modulated, respectively, 5.3% (1/19) and 57.1% (12/21) of the pathways modulated in healthy volunteers (HV), highlighting deeper alterations induced by LPS than by SEB. SEB-based clustering, identified 3 severity-based groups of septic patients significantly different regarding mHLA-DR expression and TNFα level post-LPS, as well as 28-day mortality, and nosocomial infections. Combining the results from two independent cohorts gathering 20 HV and 60 patients, 1 cluster grouped all HV with 12% of patients. The second cluster grouped 42% of patients and contained all non-survivors. The third cluster grouped 46% of patients, including 78% of those with nosocomial infections. The molecular features of these clusters indicated a distinctive contribution of previously described genes defining a “healthy-immune response” and a “sepsis-related host response”. The third cluster was characterised by potential immune recovery that underlines the possible added value of SEB-based IFA to capture the sepsis immune response and contribute to personalised management. |
| doi_str_mv | 10.1038/s41598-020-73014-2 |
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In this proof-of-concept study we characterised the underlying host immune response alterations using a standardised immune functional assay (IFA) in order to stratify a sepsis population. In septic shock patients, ex vivo LPS and SEB stimulations modulated, respectively, 5.3% (1/19) and 57.1% (12/21) of the pathways modulated in healthy volunteers (HV), highlighting deeper alterations induced by LPS than by SEB. SEB-based clustering, identified 3 severity-based groups of septic patients significantly different regarding mHLA-DR expression and TNFα level post-LPS, as well as 28-day mortality, and nosocomial infections. Combining the results from two independent cohorts gathering 20 HV and 60 patients, 1 cluster grouped all HV with 12% of patients. The second cluster grouped 42% of patients and contained all non-survivors. The third cluster grouped 46% of patients, including 78% of those with nosocomial infections. The molecular features of these clusters indicated a distinctive contribution of previously described genes defining a “healthy-immune response” and a “sepsis-related host response”. The third cluster was characterised by potential immune recovery that underlines the possible added value of SEB-based IFA to capture the sepsis immune response and contribute to personalised management.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-020-73014-2</identifier><identifier>PMID: 32999313</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/250 ; 692/53 ; Aged ; Biomarkers - blood ; Cross Infection ; Enterotoxins - immunology ; Female ; Gene Expression ; Gene Expression Profiling - methods ; Heterogeneity ; HLA-DR Antigens - metabolism ; Humanities and Social Sciences ; Humans ; Immune response ; Life Sciences ; Lipopolysaccharides ; Lipopolysaccharides - pharmacology ; Lipopolysaccharides - standards ; Male ; Middle Aged ; Monocytes - metabolism ; multidisciplinary ; Nosocomial infection ; Nosocomial infections ; Proof of Concept Study ; Science ; Science (multidisciplinary) ; Sepsis ; Sepsis - metabolism ; Septic shock ; Shock, Septic - classification ; Shock, Septic - mortality ; Shock, Septic - pathology ; Tumor Necrosis Factor-alpha - metabolism ; Tumor necrosis factor-α</subject><ispartof>Scientific reports, 2020-09, Vol.10 (1), p.16136-16136, Article 16136</ispartof><rights>The Author(s) 2020</rights><rights>The Author(s) 2020. 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In this proof-of-concept study we characterised the underlying host immune response alterations using a standardised immune functional assay (IFA) in order to stratify a sepsis population. In septic shock patients, ex vivo LPS and SEB stimulations modulated, respectively, 5.3% (1/19) and 57.1% (12/21) of the pathways modulated in healthy volunteers (HV), highlighting deeper alterations induced by LPS than by SEB. SEB-based clustering, identified 3 severity-based groups of septic patients significantly different regarding mHLA-DR expression and TNFα level post-LPS, as well as 28-day mortality, and nosocomial infections. Combining the results from two independent cohorts gathering 20 HV and 60 patients, 1 cluster grouped all HV with 12% of patients. The second cluster grouped 42% of patients and contained all non-survivors. The third cluster grouped 46% of patients, including 78% of those with nosocomial infections. 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In this proof-of-concept study we characterised the underlying host immune response alterations using a standardised immune functional assay (IFA) in order to stratify a sepsis population. In septic shock patients, ex vivo LPS and SEB stimulations modulated, respectively, 5.3% (1/19) and 57.1% (12/21) of the pathways modulated in healthy volunteers (HV), highlighting deeper alterations induced by LPS than by SEB. SEB-based clustering, identified 3 severity-based groups of septic patients significantly different regarding mHLA-DR expression and TNFα level post-LPS, as well as 28-day mortality, and nosocomial infections. Combining the results from two independent cohorts gathering 20 HV and 60 patients, 1 cluster grouped all HV with 12% of patients. The second cluster grouped 42% of patients and contained all non-survivors. The third cluster grouped 46% of patients, including 78% of those with nosocomial infections. The molecular features of these clusters indicated a distinctive contribution of previously described genes defining a “healthy-immune response” and a “sepsis-related host response”. The third cluster was characterised by potential immune recovery that underlines the possible added value of SEB-based IFA to capture the sepsis immune response and contribute to personalised management.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>32999313</pmid><doi>10.1038/s41598-020-73014-2</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-9961-5739</orcidid><orcidid>https://orcid.org/0000-0002-3821-9337</orcidid><orcidid>https://orcid.org/0000-0001-8795-0647</orcidid><orcidid>https://orcid.org/0000-0001-6439-4705</orcidid><orcidid>https://orcid.org/0000-0002-1331-096X</orcidid><orcidid>https://orcid.org/0000-0003-0462-4235</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | 631/250 692/53 Aged Biomarkers - blood Cross Infection Enterotoxins - immunology Female Gene Expression Gene Expression Profiling - methods Heterogeneity HLA-DR Antigens - metabolism Humanities and Social Sciences Humans Immune response Life Sciences Lipopolysaccharides Lipopolysaccharides - pharmacology Lipopolysaccharides - standards Male Middle Aged Monocytes - metabolism multidisciplinary Nosocomial infection Nosocomial infections Proof of Concept Study Science Science (multidisciplinary) Sepsis Sepsis - metabolism Septic shock Shock, Septic - classification Shock, Septic - mortality Shock, Septic - pathology Tumor Necrosis Factor-alpha - metabolism Tumor necrosis factor-α |
| title | Deciphering heterogeneity of septic shock patients using immune functional assays: a proof of concept study |
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