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, REALISM study group, HCL, Sophie Arnal, Caroline Augris-Mathieu, Frédérique Bayle, Liana Caruso, Charles-Éric Ber, Asma Ben-Amor, Anne-Sophie Bellocq, Farida Benatir, Anne Bertin-Maghit, M. Bertin‐Maghit, A. Boibieux, Yves Bouffard, Jean‐Christophe Cejka, Valérie Cerro, Jullien Crozon-Clauzel, Julien Davidson, Sophie Debord-Peguet, Benjamin Delwarde, Robert Deléat-Besson, Claire Delsuc, Bertrand Dévigne, Laure Fayolle-Pivot, Alexandre Faure, Bernard Floccard, Julie Gatel, Charline Genin, Thibaut Girardot, Arnaud Grégoire, 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, N. Rahali, Thomas Rimmelé, Cyrille Truc, Thomas Uberti, Hélène Vallin, Fabienne Venet, S. Tissot, Abbès Zadam, bioMérieux, 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, BIOASTER, Jérémie Becker, Frédéric Bequet, Yacine Bounab, Florian Brajon, Bertrand Canard, Muriel Collus, Nathalie Garçon, Irène Gorse, Cyril Guyard, Fabien Lavocat, Philippe Leissner, Karen Seashore Louis, Maxime Mistretta, Jeanne Morinière, Yoann Mouscaz
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.