Differential Gene Expression in Circulating CD14+ Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis
Abstract
:1. Introduction
2. Experimental Section
2.1. Patients and Controls
2.2. Isolation of Peripheral Blood Mononuclear Cells and Polymorphonuclear Cells
2.3. Flow Cytometry
2.4. Isolation of CD14+ Monocytes
2.5. Library Preparation
2.6. Standard Bioinformatic Analysis
2.7. Preparation of RNA and NanoString Analysis
2.8. Statistical Analysis
3. Results
3.1. Alterations in the Composition of Circulating Monocyte Populations and Their Surface Marker Expression in Critically Ill Patients
3.2. Gene Expression in CD14+ Monocytes from Critically Ill Patients
3.3. Enrichment of Activation Modules from Human Macrophages in Circulating Monocytes of ICU Patients
3.4. Targeted Gene Expression Analysis in Monocytes from Total Patient Cohorts
3.5. Monocytic ALOX5AP and ARHGEF10L Expression as Markers of Prognosis for ICU Patients
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Parameter | HC | SC | ICU | ICU: No Sepsis | ICU: Sepsis |
---|---|---|---|---|---|
Number, n | 54 | 42 | 76 | 40 | 36 |
Male/female, n | 30/24 | 31/11 | 45/31 | 24/16 | 21/15 |
Age (years) | 48.5 (24–77) | 65.5 (21–88) | 68 (18–97) | 60.5 (23–92) | 71 (18–97) |
Days in hospital | - | 6.5 (3–25) | 14 (1– 97) | 13 (2–89) | 20 (1–97) |
Days on ICU | - | - | 4 (1–79) | 4 (1–37) | 4 (1–79) |
Death on ICU, n (%) | - | - | 21 (27.6%) | 5 (12.5%) | 16 (44.4%) |
Death in hospital, n (%) | - | 2 (4.8%) | 28 (36.8%) | 10 (25%) | 18 (50%) |
APACHE II score | - | - | 22.5 (2–45) | 20 (2–43) | 25.5 (9–45) |
Leukocytes (per nL) | 5.8 (3.8–10.0) | 9.4 (2.1–23.0) | 13.5 (0.5–42.9) | 10.7 (2.7–31.4) | 15.5 (0.5–42.9) |
Monocytes (per nL) | 0.50 (0.25–0.95) | 0.71 (0.06–1.86) | 0.62 (0–3.45) | 0.66 (0.01–3.45) | 0.52 (0–2.16) |
IFN-γ, (pg/mL) | 4.21 (0–500) | 8.07 (0–372) | 10.6 (0–527) | 9.23 (0–101) | 20.5 (0–527) |
IL-6 (pg/mL) | 0.36 (0.2–200) | 9.25 (0.32–526) | 137 (2.4–500,000) | 56.5 (8.88–1490) | 204 (2.4–500,000) |
IL-8 (pg/mL) | 4.53 (1.71–33.8) | 7.47 (1.86–81.7) | 23.3 (0–1000) | 14.8 (0–282) | 29.3 (3.18–1000) |
TNF-α (pg/mL) | 0.57 (0–63.3) | 0.63 (0–87.2) | 1.51 (0–126) | 1.42 (0–61.9) | 1.56 (0–126) |
Cholesterol (mg/dL) | - | - | 123 (41–374) | 123 (41–374) | 128 (60–223) |
Triglyceride (mg/dL) | - | - | 139 (40–434) | 148 (40–434) | 128 (63–302) |
Site of infection, n (%) | |||||
Pulmonary | - | 14 (33.3%) | 17 (22.4%) | - | 17 (47.2%) |
Urinary | - | 17 (40.5%) | 5 (6.6%) | - | 5 (13.9%) |
Abdominal | - | 6 (14.3%) | 12 (15.8%) | - | 12 (33.3%) |
Bloodstream | - | 2 (4.8%) | 1 (1.3%) | - | 1 (2.8%) |
Other | - | 3 (7.1%) | 1 (1.3%) | - | 1 (2.8%) |
Culture positive, n (%) | - | 11 (26.2%) | 21 (27.6%) | - | 21 (58.3%) |
Gram neg., n | - | 3 | 7 | - | 7 |
Gram pos., n | - | 7 | 10 | - | 10 |
Gram pos. and neg., n | - | 0 | 3 | - | 3 |
Fungal, n | - | 1 | 1 | - | 1 |
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Liepelt, A.; Hohlstein, P.; Gussen, H.; Xue, J.; Aschenbrenner, A.C.; Ulas, T.; Buendgens, L.; Warzecha, K.T.; Bartneck, M.; Luedde, T.; et al. Differential Gene Expression in Circulating CD14+ Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis. J. Clin. Med. 2020, 9, 127. https://doi.org/10.3390/jcm9010127
Liepelt A, Hohlstein P, Gussen H, Xue J, Aschenbrenner AC, Ulas T, Buendgens L, Warzecha KT, Bartneck M, Luedde T, et al. Differential Gene Expression in Circulating CD14+ Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis. Journal of Clinical Medicine. 2020; 9(1):127. https://doi.org/10.3390/jcm9010127
Chicago/Turabian StyleLiepelt, Anke, Philipp Hohlstein, Hendrik Gussen, Jia Xue, Anna C. Aschenbrenner, Thomas Ulas, Lukas Buendgens, Klaudia T. Warzecha, Matthias Bartneck, Tom Luedde, and et al. 2020. "Differential Gene Expression in Circulating CD14+ Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis" Journal of Clinical Medicine 9, no. 1: 127. https://doi.org/10.3390/jcm9010127