Chronic Critical Illness Elicits a Unique Circulating Leukocyte Transcriptome in Sepsis Survivors

Autor:	Philip A. Efron, Henry V. Baker, Tezcan Ozrazgat-Baslanti, Lyle L. Moldawer, Maria-Cecilia Lopez, Rhonda Bacher, Tyler J. Loftus, Alicia M. Mohr, Michael C. Cox, Scott C. Brakenridge, Dijoia B Darden, Gabriela L. Ghita, Azra Bihorac, Christiaan Leeuwenburgh, Frederick A. Moore, Jaimar Rincon, Zhongkai Wang, Russell B. Hawkins, Lauren S Kelly, Brittany P Fenner, Julie A. Stortz
Jazyk:	angličtina
Rok vydání:	2021
Předmět:	leukocytes Dyscrasia Article Sepsis Transcriptome sepsis immunology 03 medical and health sciences 0302 clinical medicine Immune system Medicine 030212 general & internal medicine human Prospective cohort study Whole blood business.industry Organ dysfunction 030208 emergency & critical care medicine General Medicine medicine.disease nervous system diseases Critical illness Immunology RNA medicine.symptom business transcriptome
Zdroj:	Journal of Clinical Medicine Volume 10 Issue 15 Journal of Clinical Medicine, Vol 10, Iss 3211, p 3211 (2021)
ISSN:	2077-0383
DOI:	10.3390/jcm10153211
Popis:	Surgical sepsis has evolved into two major subpopulations: patients who rapidly recover, and those who develop chronic critical illness (CCI). Our primary aim was to determine whether CCI sepsis survivors manifest unique blood leukocyte transcriptomes in late sepsis that differ from transcriptomes among sepsis survivors with rapid recovery. In a prospective cohort study of surgical ICU patients, genome-wide expression analysis was conducted on total leukocytes in human whole blood collected on days 1 and 14 from sepsis survivors who rapidly recovered or developed CCI, defined as ICU length of stay ≥ 14 days with persistent organ dysfunction. Both sepsis patients who developed CCI and those who rapidly recovered exhibited marked changes in genome-wide expression at day 1 which remained abnormal through day 14. Although summary changes in gene expression were similar between CCI patients and subjects who rapidly recovered, CCI patients exhibited differential expression of 185 unique genes compared with rapid recovery patients at day 14 (p < 0.001). The transcriptomic patterns in sepsis survivors reveal an ongoing immune dyscrasia at the level of the blood leukocyte transcriptome, consistent with persistent inflammation and immune suppression. Furthermore, the findings highlight important genes that could compose a prognostic transcriptomic metric or serve as therapeutic targets among sepsis patients that develop CCI.
Databáze:	OpenAIRE
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