Integrated clustering of multiple immune marker trajectories reveals different immunotypes in severely injured patients

Maxime Bodinier; Estelle Peronnet; Jean-François Llitjos; Louis Kreitmann; Karen Brengel-Pesce; Thomas Rimmelé; Aurore Fleurie; Julien Textoris; Fabienne Venet; Delphine Maucort-Boulch; Guillaume Monneret; Sophie Arnal; Caroline Augris-Mathieu; Frédérique Bayle; Liana Caruso; Charles-Eric Ber; Asma Ben-Amor; Anne-Sophie Bellocq; Farida Benatir; Anne Bertin-Maghit; Marc Bertin-Maghit; André Boibieux; Yves Bouffard; Jean-Christophe Cejka; Valérie Cerro; Jullien Crozon-Clauzel; Julien Davidson; Sophie Debord-Peguet; Benjamin Delwarde; Robert Deleat-Besson; Claire Delsuc; Bertrand Devigne; Laure Fayolle-Pivot; Alexandre Faure; Bernard Floccard; Julie Gatel; Charline Genin; Thibaut Girardot; Arnaud Gregoire; Baptiste Hengy; Laetitia Huriaux; Catherine Jadaud; Alain Lepape; Véronique Leray; Anne-Claire Lukaszewicz; Guillaume Marcotte; Olivier Martin; Marie Matray; Delphine Maucort-Boulch; Pascal Meuret; Céline Monard; Florent Moriceau; Guillaume Monneret; Nathalie Panel; Najia Rahali; Thomas Rimmele; Cyrille Truc; Thomas Uberti; Hélène Vallin; Fabienne Venet; Sylvie Tissot; Abbès Zadam; Sophie Blein; Karen Brengel-Pesce; Elisabeth Cerrato; Valérie Cheynet; Emmanuelle Gallet-Gorius; Audrey Guichard; Camille Jourdan; Natacha Koenig; François Mallet; Boris Meunier; Virginie Moucadel; Marine Mommert; Guy Oriol; Alexandre Pachot; Estelle Peronnet; Claire Schrevel; Olivier Tabone; Julien Textoris; Javier Yugueros Marcos; Jérémie Becker; Frédéric Bequet; Yacine Bounab; Florian Brajon; Bertrand Canard; Muriel Collus; Nathalie Garcon; Irène Gorse; Cyril Guyard; Fabien Lavocat; Philippe Leissner; Karen Louis; Maxime Mistretta; Jeanne Moriniere; Yoann Mouscaz; Laura Noailles; Magali Perret; Frédéric Reynier; Cindy Riffaud; Mary-Luz Rol; Nicolas Sapay; Trang Tran; Christophe Vedrine; Christophe Carre; Pierre Cortez; Aymeric de Monfort; Karine Florin; Laurent Fraisse; Isabelle Fugier; Sandrine Payrard; Annick Peleraux; Laurence Quemeneur; Andrew Griffiths; Stephanie Toetsch; Teri Ashton; Peter Gough; Scott Berger; David Gardiner; Iain Gillespie; Aidan Macnamara; Aparna Raychaudhuri; Rob Smylie; Lionel Tan; Craig Tipple

doi:10.1186/s13054-024-04990-4

Journal Articles Critical Care Year : 2024

Integrated clustering of multiple immune marker trajectories reveals different immunotypes in severely injured patients

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Maxime Bodinier

Function : Author

Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression

Bio-Mérieux [Marcy l'Etoile]

Hospices Civils de Lyon

Estelle Peronnet

Function : Author

Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression

Bio-Mérieux [Marcy l'Etoile]

Hospices Civils de Lyon

Jean-François Llitjos

Function : Author

Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression

Bio-Mérieux [Marcy l'Etoile]

Hospices Civils de Lyon

Hôpital Edouard Herriot [CHU - HCL]

Louis Kreitmann

Function : Author

Hammersmith Hospital NHS Imperial College Healthcare

Imperial College London

Karen Brengel-Pesce

Function : Author

Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression

Bio-Mérieux [Marcy l'Etoile]

Hospices Civils de Lyon

Thomas Rimmelé

Function : Author

Centre Lyonnais d'Enseignement par Simulation en Santé [Lyon]

Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression

Service d'anesthésie-réanimation [Lyon]

Aurore Fleurie

Function : Author

Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression

Bio-Mérieux [Marcy l'Etoile]

Hospices Civils de Lyon

Julien Textoris

Function : Author

Bio-Mérieux [Marcy l'Etoile]

Anesthesiology and Intensive Care Department, Hospices Civils de Lyon, Edouard Herriot Hospital, Lyon, France

Fabienne Venet

Function : Author

Centre International de Recherche en Infectiologie

Inflammasome NLRP3 et réponse immunitaire au sepsis - NLRP3 inflammasome and immune response to sepsis [CIRI]

Delphine Maucort-Boulch

Function : Author
PersonId : 1267466
IdHAL : delphine-maucort-boulch
ORCID : 0000-0003-0042-7787
IdRef : 094595771

Laboratoire de Biométrie et Biologie Evolutive - UMR 5558

Hospices Civils de Lyon

Service de Biostatistiques [Lyon]

Guillaume Monneret

Function : Author

Bio-Mérieux [Marcy l'Etoile]

Hospices Civils de Lyon, Immunology Laboratory, Edouard Herriot Hospital, Lyon, France

Sophie Arnal

Function : Author

Caroline Augris-Mathieu

Function : Author

Frédérique Bayle

Function : Author

Anesthesia and Critical Care Medicine Department, Hospices Civils de Lyon, Edouard Herriot Hospital, 69437, Lyon, France.

Liana Caruso

Function : Author

Charles-Eric Ber

Function : Author

Hôpital Edouard Herriot [CHU - HCL]

Asma Ben-Amor

Function : Author

Anne-Sophie Bellocq

Function : Author

Farida Benatir

Function : Author

Anne Bertin-Maghit

Function : Author

Marc Bertin-Maghit

Function : Author

Hospices Civils de Lyon, Burn Ward, Intensive Care Unit, Hôpital E Herriot, Pavillon I - 5 place d'Arsonval, Lyon, Cedex 03 69437, France

André Boibieux

Function : Author

Yves Bouffard

Function : Author

Jean-Christophe Cejka

Function : Author

Valérie Cerro

Function : Author

Jullien Crozon-Clauzel

Function : Author

Julien Davidson

Function : Author

Sophie Debord-Peguet

Function : Author

Benjamin Delwarde

Function : Author

Robert Deleat-Besson

Function : Author

Claire Delsuc

Function : Author

Bertrand Devigne

Function : Author

Laure Fayolle-Pivot

Function : Author

Alexandre Faure

Function : Author

Bernard Floccard

Function : Author

Julie Gatel

Function : Author

Charline Genin

Function : Author

Thibaut Girardot

Function : Author

Arnaud Gregoire

Function : Author

Baptiste Hengy

Function : Author

Laetitia Huriaux

Function : Author

Catherine Jadaud

Function : Author

Alain Lepape

Function : Author

Véronique Leray

Function : Author

Anne-Claire Lukaszewicz

Function : Author

Guillaume Marcotte

Function : Author

Olivier Martin

Function : Author

Marie Matray

Function : Author

Delphine Maucort-Boulch

Function : Author

Laboratoire de Biométrie et Biologie Evolutive - UMR 5558

Hospices Civils de Lyon

Service de Biostatistiques [Lyon]

Pascal Meuret

Function : Author

Céline Monard

Function : Author

Florent Moriceau

Function : Author

Guillaume Monneret

Function : Author

Nathalie Panel

Function : Author

Najia Rahali

Function : Author

Thomas Rimmele

Function : Author

Cyrille Truc

Function : Author

Thomas Uberti

Function : Author

Hélène Vallin

Function : Author

Fabienne Venet

Function : Author

Sylvie Tissot

Function : Author

Abbès Zadam

Function : Author

Sophie Blein

Function : Author

Karen Brengel-Pesce

Function : Author

Elisabeth Cerrato

Function : Author

Valérie Cheynet

Function : Author

Emmanuelle Gallet-Gorius

Function : Author

Audrey Guichard

Function : Author

Camille Jourdan

Function : Author

Natacha Koenig

Function : Author

François Mallet

Function : Author

Boris Meunier

Function : Author

Virginie Moucadel

Function : Author

Marine Mommert

Function : Author

Guy Oriol

Function : Author

Alexandre Pachot

Function : Author

Estelle Peronnet

Function : Author

Claire Schrevel

Function : Author

Olivier Tabone

Function : Author

Julien Textoris

Function : Author

Javier Yugueros Marcos

Function : Author

Jérémie Becker

Function : Author

Frédéric Bequet

Function : Author

Yacine Bounab

Function : Author

Florian Brajon

Function : Author

Bertrand Canard

Function : Author

Muriel Collus

Function : Author

Nathalie Garcon

Function : Author

Irène Gorse

Function : Author

Cyril Guyard

Function : Author

Fabien Lavocat

Function : Author

Philippe Leissner

Function : Author

Karen Louis

Function : Author

Maxime Mistretta

Function : Author

Jeanne Moriniere

Function : Author

Yoann Mouscaz

Function : Author

Laura Noailles

Function : Author

Magali Perret

Function : Author

Frédéric Reynier

Function : Author

Cindy Riffaud

Function : Author

Mary-Luz Rol

Function : Author

Nicolas Sapay

Function : Author

Trang Tran

Function : Author

Christophe Vedrine

Function : Author

Christophe Carre

Function : Author

Pierre Cortez

Function : Author

Aymeric de Monfort

Function : Author

Karine Florin

Function : Author

Laurent Fraisse

Function : Author

Isabelle Fugier

Function : Author

Sandrine Payrard

Function : Author

Annick Peleraux

Function : Author

Laurence Quemeneur

Function : Author

Andrew Griffiths

Function : Author

Stephanie Toetsch

Function : Author

Teri Ashton

Function : Author

Peter Gough

Function : Author

Scott Berger

Function : Author

David Gardiner

Function : Author

Iain Gillespie

Function : Author

Aidan Macnamara

Function : Author

Aparna Raychaudhuri

Function : Author

Rob Smylie

Function : Author

Lionel Tan

Function : Author

Craig Tipple

Function : Author

Abstract

Abstract Background The immune response of critically ill patients, such as those with sepsis, severe trauma, or major surgery, is heterogeneous and dynamic, but its characterization and impact on outcomes are poorly understood. Until now, the primary challenge in advancing our understanding of the disease has been to concurrently address both multiparametric and temporal aspects. Methods We used a clustering method to identify distinct groups of patients, based on various immune marker trajectories during the first week after admission to ICU. In 339 severely injured patients, we initially longitudinally clustered common biomarkers (both soluble and cellular parameters), whose variations are well-established during the immunosuppressive phase of sepsis. We then applied this multi-trajectory clustering using markers composed of whole blood immune-related mRNA. Results We found that both sets of markers revealed two immunotypes, one of which was associated with worse outcomes, such as increased risk of hospital-acquired infection and mortality, and prolonged hospital stays. This immunotype showed signs of both hyperinflammation and immunosuppression, which persisted over time. Conclusion Our study suggest that the immune system of critically ill patients can be characterized by two distinct longitudinal immunotypes, one of which included patients with a persistently dysregulated and impaired immune response. This work confirms the relevance of such methodology to stratify patients and pave the way for further studies using markers indicative of potential immunomodulatory drug targets. Graphical Abstract

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https://hal.science/hal-04669222

Submitted on : Thursday, August 8, 2024-9:33:42 AM

Last modification on : Friday, August 9, 2024-3:16:44 AM

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hal-04669222 , version 1 (08-08-2024)

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HAL Id : hal-04669222 , version 1
DOI : 10.1186/s13054-024-04990-4

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Maxime Bodinier, Estelle Peronnet, Jean-François Llitjos, Louis Kreitmann, Karen Brengel-Pesce, et al.. Integrated clustering of multiple immune marker trajectories reveals different immunotypes in severely injured patients. Critical Care, 2024, 28 (1), pp.240. ⟨10.1186/s13054-024-04990-4⟩. ⟨hal-04669222⟩

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Integrated clustering of multiple immune marker trajectories reveals different immunotypes in severely injured patients

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