Objective:

To investigate the association of peripheral blood expression of LUBAC and OTULIN with stroke severity and functional outcome in acute ischemic stroke (AIS) patients, highlighting their potential role as biomarkers.

Key Findings:

• Increased LUBAC and OTULIN expression was observed in the peri-ischemic cortex.
• Peripheral blood HOIP and OTULIN levels were significantly higher in AIS patients compared to healthy controls (P < 0.001).
• HOIP was positively associated with stroke severity (β = 1.928, P < 0.001) and poor outcome (OR = 5.360, P = 0.013).
• OTULIN was negatively associated with stroke severity (β = -1.060, P < 0.001), but not significantly associated with poor outcome (P = 0.119).
• HOIP showed good discriminative ability for poor outcome (AUC = 0.832), and its inclusion improved model calibration (referring to the model's accuracy and reliability) and clinical net benefit.

Interpretation:

Peripheral blood levels of HOIP and OTULIN may serve as biomarkers for stroke severity in AIS, with HOIP providing additional prognostic information for functional outcomes, potentially guiding treatment decisions.

Limitations:

• The study's sample size may limit the generalizability of the findings, particularly in diverse populations.
• The observational nature of the study does not establish causation, which should be considered when interpreting the results.

Conclusion:

HOIP and OTULIN could be potential biomarkers for assessing stroke severity and prognosis in AIS patients, which may enhance clinical decision-making.