• Estelle Peronnet, Sophie Blein, Fabienne Venet, Elisabeth Cerrato, Aurore Fleurie, Jean-François Llitjos, Louis Kreitmann, Gabriel Terraz, Filippo Conti, Morgane Gossez, Thomas Rimmelé, Julien Textoris, Anne-Claire Lukaszewicz, Karen Brengel-Pesce, Guillaume Monneret, and REAnimation Low Immune Status Marker (REALISM) Study Group.
• Joint Research Unit HCL-bioMérieux, EA 7426 "Pathophysiology of Injury-Induced Immunosuppression" (Université Claude Bernard Lyon 1 - Hospices Civils de Lyon, bioMérieux), Lyon, France.
• Crit. Care Med. 2023 Jun 1; 51 (6): 808816808-816.

ObjectivesThere is a crucial unmet need for biomarker-guided diagnostic and prognostic enrichment in clinical trials evaluating immune modulating therapies in critically ill patients. Low monocyte expression of human leukocyte antigen-DR (mHLA-DR), considered as a reference surrogate to identify immunosuppressed patients, has been proposed for patient stratification in immunostimulation approaches. However, its widespread use in clinic has been somewhat hampered by technical constraints inherent to flow cytometry technology. The objective of the present study was to evaluate the ability of a prototype multiplex polymerase chain reaction tool (immune profiling panel [IPP]) to identify immunosuppressed ICU patients characterized by a low mHLA-DR expression.DesignRetrospective observational cohort study.SettingAdult ICU in a University Hospital, Lyon, France.PatientsCritically ill patients with various etiologies enrolled in the REAnimation Low Immune Status Marker study (NCT02638779).InterventionsNone.Measurements And Main ResultsmHLA-DR and IPP data were obtained from 1,731 blood samples collected from critically ill patients with various etiologies and healthy volunteers. A partial least square regression model combining the expression levels of IPP markers was trained and used for the identification of samples from patients presenting with evidence of immunosuppression, defined here as mHLADR less than 8,000 antibodies bound per cell (AB/C). The IPP gene set had an area under the receiver operating characteristic curve (AUC) of 0.86 (95% CI 0.83-0.89) for the identification of immunosuppressed patients. In addition, when applied to the 123 patients still in the ICU at days 5-7 after admission, IPP similarly enriched the number of patients with ICU-acquired infections in the immunosuppressed group (26%), in comparison with low mHLA-DR (22%).ConclusionsThis study reports on the potential of the IPP gene set to identify ICU patients presenting with mHLA-DR less than 8,000 AB/C. Upon further optimization and validation, this molecular tool may help in the stratification of patients that could benefit from immunostimulation in the context of personalized medicine.Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.

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