ArticleFrontiers in immunology2026
Association of peripheral blood LUBAC and OTULIN expression with severity and outcome in acute ischemic stroke: a prospective cohort study.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: This study investigated whether peripheral blood expression of linear ubiquitin chain assembly complex (LUBAC) and OTU deubiquitinase with linear linkage specificity (OTULIN) is associated with stroke severity and functional outcome in acute ischemic stroke (AIS) patients. Methods: Immunofluorescence for LUBAC and OTULIN was performed in cortical autopsy specimens from two AIS cases. A total of 100 AIS patients and 100 age- and sex-matched healthy controls were enrolled. Peripheral blood mRNA levels of OTULIN and LUBAC components, including HOIL-1 interacting protein (HOIP), heme-oxidized IRP2 ubiquitin ligase 1L (HOIL-1L), and SHANK-associated RH domain interactor (SHARPIN), were quantified using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Stroke severity at admission was assessed using the National Institutes of Health Stroke Scale (NIHSS). Functional outcome was evaluated using the modified Rankin Scale (mRS) at 90 ± 7 days. Regression models were used to evaluate associations of HOIP and OTULIN with stroke severity and outcome after adjustment for confounders. A HOIP × OTULIN interaction term was applied to assess effect modification. Discrimination for unfavorable outcome (mRS >2) was assessed using receiver operating characteristic (ROC) analysis. Results: Immunofluorescence suggested increased LUBAC and OTULIN expression in the peri-ischemic cortex. Peripheral blood HOIP and OTULIN expression levels were significantly higher in AIS patients than in healthy controls (P < 0.001). After adjustment for potential confounders, HOIP was independently positively associated with stroke severity (β = 1.928, P < 0.001) and independently associated with poor outcome (OR = 5.360, P = 0.013). OTULIN was just independently negatively associated with stroke severity (β = -1.060, P < 0.001), but its independent association with poor outcome was not statistically significant (P = 0.119). Interaction analysis showed a significant interaction between HOIP and OTULIN on stroke severity. ROC analysis showed that HOIP had good discriminative ability for poor outcome (AUC = 0.832). Adding HOIP to the clinical model increased the AUC from 0.846 to 0.907 and further improved model calibration and clinical net benefit. Conclusion: Peripheral blood HOIP and OTULIN may serve as candidate biomarkers associated with stroke severity in AIS, while HOIP may provide additional prognostic information for functional outcome.
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