Association of the TREM‐1–STAT3 Axis With Stroke Severity and Functional Outcomes in Ischemic Stroke: A Prospective Case‐Control Study

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BACKGROUND: Information regarding the signaling axis involving triggering receptor expressed on myeloid cells 1 (TREM-1) and its downstream mediator, signal transducer and activator of transcription 3 (STAT3), remains limited in ischemic stroke. We investigated the plasma levels of TREM-1 in patients with ischemic stroke and compared to controls. Second, we investigated the potential correlation between plasma TREM-1 levels and STAT3 expression in peripheral blood mononuclear cells (PBMCs) and explored their associations with stroke severity and functional outcomes. METHODS: In an observational case-control study, plasma and PBMCs from participants were collected to measure TREM-1 and STAT3 expression levels. The National Institutes of Health Stroke Scale (NIHSS) at admission, day 7, and 1 and 3 months, and the modified Rankin Scale (mRS) at 3 months post-discharge were assessed. Plasma TREM-1 levels and STAT3 expression were measured by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (RT-qPCR), respectively. The Inflammation-Related Principal Component Score (IRPCS) was examined for its association with 3-month functional outcome. RESULT: TREM-1 and STAT3 were significantly elevated in acute ischemic stroke (AIS) patients (p < 0.05, p < 0.0001) and positively correlated (ρ = 0.432, p < 0.0001). Both biomarkers correlated with the NIHSS at 1 and 3 months and mRS at 3 months (all p < 0.05). The composite IRPCS showed the strongest association with poor 3-month functional outcome among the tested biomarkers (OR = 2.84, 95% CI: 1.32-6.12, p = 0.008). CONCLUSION: Plasma TREM-1 levels were positively correlated with STAT3 expression. The TREM-1-STAT3 axis was associated with stroke severity and 3-month functional outcome in AIS patients. These findings should be regarded as exploratory and require validation in larger cohorts.

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