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Published on: June 2, 2022
High Levels of Triggering Receptor Expressed in Myeloid Cells-Like Transcript-1 Positive, but Not Glycoprotein 1b+,
Angelia D Gibson1, Zaida Bayrón-Marrero2, Benjamin Nieves-Lopez3
1Division of Natural Sciences, Maryville College, Maryville, TN.
Objectives:
To identify triggering receptor expressed in myeloid cells-like transcript-1 positive (TLT-1+) microparticles (MPs) and evaluate if their presence is associated with clinical outcomes and/or disease severity in acute respiratory distress syndrome (ARDS).
Design:
Retrospective cohort study.
Setting:
ARDS Network clinical trials.
Patients:
A total of 564 patients were diagnosed with ARDS.
Interventions:
None.
Measurements And Main Results:
Using flow cytometry, we demonstrated the presence of TLT-1+ platelet-derived microparticles (PMP) that bind fibrinogen in plasma samples from fresh donors. We retrospectively quantified TLT-1, glycoprotein (Gp) 1b, or αIIbβIIIa immunopositive microparticles in plasma samples from patients with ARDS enrolled in the ARMA, KARMA, and LARMA (Studies 01 and 03 lower versus higher tidal volume, ketoconazole treatment, and lisofylline treatment Clincial Trials) ARDS Network clinical trials and evaluated the relationship between these measures and clinical outcomes. No associations were found between Gp1b+ MPs and clinical outcomes for any of the cohorts. When stratified by quartile, associations were found for survival, ventilation-free breathing, and thrombocytopenia with αIIbβIIIa+ and TLT-1+ MPs (χ2p < 0.001). Notably, 63 of 64 patients in this study who failed to achieve unassisted breathing had TLT+ PMP in the 75th percentile. In all three cohorts, patients whose TLT+ MP counts were higher than the median had higher Acute Physiology and Chronic Health Evaluation III scores, were more likely to present with thrombocytopenia and were 3.7 times (p < 0.001) more likely to die than patients with lower TLT+ PMP after adjusting for other risk factors.
Conclusions:
Although both αIIbβIIIa+ and TLT+ microparticles (αIIbβIIIa, TLT-1) were associated with mortality, TLT-1+ MPs demonstrated stronger correlations with Acute Physiology and Chronic Health Evaluation III scores, unassisted breathing, and multiple system organ failure. These findings warrant further exploration of the mechanistic role of TLT-1+ PMP in ARDS or acute lung injury progression.
Insights
Triggering receptor expressed in myeloid cells-like transcript-1 positive (TLT-1+) microparticles (MPs) are associated with worse outcomes in acute respiratory distress syndrome (ARDS). Higher TLT-1+ MP levels correlate with increased mortality and disease severity in ARDS patients.
Area of Science:
- Hematology
- Immunology
- Critical Care Medicine
Background:
- Microparticles (MPs) are small vesicles released from cell membranes.
- Platelet-derived microparticles (PMPs) play roles in hemostasis and inflammation.
- Triggering receptor expressed in myeloid cells-like transcript-1 (TLT-1) is a protein found on certain cells.
Purpose of the Study:
- To identify TLT-1 positive (TLT-1+) microparticles (MPs).
- To evaluate the association between TLT-1+ MPs and clinical outcomes in acute respiratory distress syndrome (ARDS).
- To assess the relationship between TLT-1+ MPs and ARDS disease severity.
Main Methods:
- Retrospective cohort study utilizing ARDS Network clinical trial data.
- Flow cytometry was used to detect TLT-1+ MPs.
- Quantification of TLT-1, glycoprotein (Gp) 1b, and αIIbβIIIa immunopositive MPs in ARDS patients.
Main Results:
- TLT-1+ MPs were identified and found to bind fibrinogen.
- No association was observed between Gp1b+ MPs and clinical outcomes.
- Higher levels of TLT-1+ MPs correlated significantly with increased mortality, higher Acute Physiology and Chronic Health Evaluation III scores, and a greater likelihood of thrombocytopenia in ARDS patients.
Conclusions:
- TLT-1+ MPs are associated with mortality and disease severity in ARDS.
- TLT-1+ MPs showed stronger correlations with clinical outcomes than αIIbβIIIa+ MPs.
- Further research is warranted to elucidate the mechanistic role of TLT-1+ PMPs in ARDS progression.
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