The Expression of High Mobility Group Box-1 (HMG1) in the Peripheral Blood and its Relation with Systemic Vasculitis Patients

Background: We aimed to explore the expression of high mobility group box-1 (HMG1) in the peripheral blood of systemic vasculitis (SV) patients. Methods: The peripheral blood were collected from 35 healthy controls and 35 SV patients, and the expressions of HMGB1 and pyroptosis-related markers in the samples were detected by ELISA. They were admitted to the Department of Rheumatology and Immunology of the Third Affiliated Hospital of Qiqihar Medical University, China in 2022. The severity of diseases was graded according to the diagnosis and treatment norms of SV. The correlation between HMGB1 expression level and disease-related indicators and grades were explored through Pearson correlation analysis. The specific mechanism of HMGB1 mediating the occurrence and development of diseases through the regulation of endothelial pyroptosis was clarified. Results: HMGB1 expression significantly increased in the peripheral blood of SV patients compared with healthy controls (P<0.0001). Pearson correlation analysis indicated that HMGB1 expression level in serum gradually increased with the aggravation in SV patients. The expression levels of ASC (P<0.0001), IL-1β (P=0.004) and IL-18 (P<0.0001) in peripheral blood of SV patients were significantly increased, which were significantly positively correlated with HMGB1 in peripheral blood (P<0.0001). Recombinant HMGB1 significantly promoted the expression of ASC, IL-1β and IL-18 in vascular endothelial cells. Recombinant HMGB1 stimulation significantly activated NLRP3 inflammasome, and the additional addition of NLRP3 inhibitor significantly inhibited HMGB1-mediated endothelial pyroptosis. Conclusion: HMGB1 expression was significantly high in the peripheral blood of SV patients, which was positively correlated with the severity of diseases. HMGB1 could mediate pyroptosis through activating TLR4/NF-κB/NLRP3 signaling pathway.