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Caspase-1 Activation in Monocyte Subsets Is Associated with Monocyte Distribution Width
Yin Liu1, Fei Pei2, Dong Wang1,3
1Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Background:
Monocyte distribution width (MDW) is a robust early sepsis biomarker. However, the mechanism underlying MDW elevation remains unclear. We evaluated the associations of MDW with monocyte subset proportions (based on CD14/CD16 expression) and caspase-1 activation levels.
Methods:
In total, 98 adults (22 healthy controls, 25 patients with mild infection, 16 non-sepsis intensive care unit patients, and 35 patients with sepsis) were included in this prospective observational study. MDW was measured alongside routine complete blood count (CBC) using a UniCel DxH 800 analyzer (Beckman Coulter). Caspase-1 activity in monocyte subsets was assessed using flow cytometry with Fluorescent Labeled Inhibitor of Caspase- 1 (Immunochemistry Technologies) and quantified as geometric mean fluorescence intensity.
Results:
Compared with healthy controls, all patient groups showed reduced classical monocyte frequencies and increased intermediate monocyte frequencies; these variations were moderately associated with elevated MDW. Caspase-1 activity was elevated in all three monocyte subsets across patient groups; patients with sepsis showed significantly higher non-classical monocyte activity than the other two patient cohorts. MDW correlated positively with caspase-1 activity in all subsets, with the strongest correlation in non-classical monocytes (Spearman's ρ=0.762, P <0.001).
Conclusions:
Elevated MDW correlates with altered monocyte subset proportions and enhanced in vivo caspase-1 activation, with a particularly strong association with non-classical monocyte caspase-1 activity. Given that non-classical monocyte caspase-1 activity is markedly increased in patients with sepsis, our results suggest a potential clinically relevant association linking MDW to sepsis-associated monocyte dysfunction, which may inform the interpretation of MDW in clinical practice.
Insights
Monocyte distribution width (MDW) elevation in sepsis is linked to changes in monocyte subsets and increased caspase-1 activity. This suggests MDW may reflect sepsis-related monocyte dysfunction.
Area of Science:
- Hematology
- Immunology
- Biomarker Research
Background:
- Monocyte distribution width (MDW) is an early sepsis biomarker, but its underlying mechanisms are not fully understood.
- Investigating the relationship between MDW and monocyte characteristics is crucial for interpreting its clinical significance.
Purpose of the Study:
- To explore the association between MDW and monocyte subset proportions (classical, intermediate, non-classical).
- To examine the link between MDW and caspase-1 activation levels within monocyte subsets.
Main Methods:
- Prospective observational study including healthy controls and patients with infection or sepsis.
- MDW measured via complete blood count (CBC); monocyte subset analysis and caspase-1 activity assessed by flow cytometry.
Main Results:
- Elevated MDW showed moderate associations with altered classical and intermediate monocyte frequencies.
- Caspase-1 activity was increased in all monocyte subsets in patients, particularly non-classical monocytes in sepsis.
- MDW positively correlated with caspase-1 activity across all monocyte subsets, strongest in non-classical monocytes.
Conclusions:
- Elevated MDW correlates with altered monocyte subset distribution and increased caspase-1 activation.
- The strong link between MDW and non-classical monocyte caspase-1 activity suggests a connection to sepsis-associated monocyte dysfunction.
- Findings may aid in the clinical interpretation of MDW in sepsis diagnosis and management.
