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Low Interleukin-7 Receptor Messenger RNA Expression Is Independently Associated With Day 28 Mortality in Septic Shock Patients*

Title: Low Interleukin-7 Receptor Messenger RNA Expression Is Independently Associated With Day 28 Mortality in Septic Shock Patients*
Authors: Delwarde, Benjamin; Peronnet, Estelle; Venet, Fabienne; Cerrato, Elisabeth; Meunier, Boris; Mouillaux, Julie; Lepape, Alain; Pachot, Alexandre; Rimmelé, Thomas; Monneret, Guillaume; Textoris, Julien
Contributors: Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques / Pathophysiology of Injury-induced Immunosuppression (PI3); Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université de Lyon; Université de Lyon; Hospices Civils de Lyon – Immunology Laboratory, Hôpital Edouard Herriot, Lyon, France; Intensive Care Unit, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Chemin du Grand Revoyet, 69495 Pierre-Bénite, France.; Anaesthesiology and Intensive Care Medicine Department, Hospices Civils de Lyon, Hôpital Edouard Herriot, Lyon, France.; Immunology Laboratory, Hospices Civils De Lyon, Hôpital Edouard Herriot, Lyon, F 69003, France
Source: ISSN: 0090-3493.
Publisher Information: CCSD; Lippincott, Williams & Wilkins
Publication Year: 2018
Collection: Université de Lyon: HAL
Subject Terms: Septic shock; interleukin-7 receptor; Intensive care units; gene expression; biomarkers; [SDV]Life Sciences [q-bio]
Description: International audience ; Septic shock is the primary cause of death in ICUs. A better comprehension of its pathophysiology, in particular, the immune alteration mechanisms, opened new therapeutic perspectives such as the recombinant interleukin-7. The use of biomarkers could improve the identification of eligible patients for this therapy. The soluble form of the interleukin-7 appears as a promising candidate in this regard since an association between its high plasmatic level and mortality in critically ill patients has been demonstrated. Because there are no data available on the transcriptional regulation of the interleukin-7 receptor in such patients, this study aimed to explore the expression level of different interleukin-7 receptor transcripts after septic shock and evaluate their association with mortality. Retrospective discovery cohort (30 patients) and validation cohort (177 patients). Two French ICUs (discovery study) and six French ICUs (validation study). Adult septic shock patients. Interventions: None. Measurements and Main Results: The quantification of several interleukin-7 receptor transcripts using specific reverse transcription quantitative polymerase chain reaction designs allowed for global evaluation of interleukin-7 receptor gene expression in whole blood. In the discovery cohort, all interleukin-7 receptor transcripts studied were expressed at lower levels in septic shock patients than in healthy volunteers. Interleukin-7 receptor gene expression at day 3 after septic shock diagnosis was associated with day 28 mortality. Patients at a lower risk of death showed higher expression levels. These results were confirmed in the independent validation cohort. Interestingly, using a threshold obtained on the discovery cohort, we observed in the validation cohort a high negative predictive value for day 28 mortality for the transcript encoding the membrane form of interleukin-7 receptor (0.86; 95% CI, 0.79–0.93). Conclusions: Interleukin-7 receptor transcripts appear as biomarkers of impaired ...
Document Type: article in journal/newspaper
Language: English
DOI: 10.1097/ccm.0000000000003281
Availability: https://hal.science/hal-04930200; https://hal.science/hal-04930200v1/document; https://hal.science/hal-04930200v1/file/low_interleukin_7_receptor_messenger_rna.4.pdf; https://doi.org/10.1097/ccm.0000000000003281
Rights: https://creativecommons.org/licenses/by-nc-nd/4.0/ ; info:eu-repo/semantics/OpenAccess
Accession Number: edsbas.29BFC37E
Database: BASE