The leukocyte non-coding RNA landscape in critically ill patients with sepsis

• DOI: 10.7554/elife.58597
• Publication Date: 2020-12-11T13:04:53Z
• Authors: Brendon P Scicluna; Fabrice Uhel; Lonneke A van Vught; Maryse A Wiewel; Arie J Hoogendijk; Ingelore Baessman; Marek Franitza; Peter Nürnberg; Janneke Horn; Olaf L Cremer; Marc J Bonten; Marcus J Schultz; Tom van der Poll
• Keywords: Septicemia -- Diagnosis; Male; RNA, Untranslated; QH301-705.5; Science; Critical Illness; Immunology; non-coding RNA; sepsis; 03 medical and health sciences; Immunology and Inflammation; Sepsis; Human beings; Leukocytes; Humans; Biology (General); Inflammation -- Immunological aspects; Leucocytes; Non-coding RNA; Aged; Oligonucleotide Array Sequence Analysis; 0303 health sciences; Q; R; Middle Aged; Endotoxemia; 3. Good health; Case-Control Studies; Medicine; Female; Transcriptome; leukocyte

The extent of non-coding RNA alterations in patients with sepsis and their relationship to clinical characteristics, soluble mediators of the host response to infection, as well as an advocated in vivo model of acute systemic inflammation is unknown. Here we obtained whole blood from 156 patients with sepsis and 82 healthy subjects among whom eight were challenged with lipopolysaccharide in a clinically controlled setting (human endotoxemia). Via next-generation microarray analysis of leukocyte RNA we found that long non-coding RNA and, to a lesser extent, small non-coding RNA were significantly altered in sepsis relative to health. Long non-coding RNA expression, but not small non-coding RNA, was largely recapitulated in human endotoxemia. Integrating RNA profiles and plasma protein levels revealed known as well as previously unobserved pathways, including non-sensory olfactory receptor activity. We provide a benchmark dissection of the blood leukocyte ‘regulome’ that can facilitate prioritization of future functional studies.