Original Article

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.

1. Dharma P, Sharma S, Baltaro R, et al (2011). Systemic vasculitis. Am Fam Physi-cian, 83(5): 556-565.
2. Koening CL (2013). New concepts in the pathogenesis and treatment of vasculitis syndromes. Curr Opin Rheumatol, 25(1): 2.
3. Moiseev S, Cohen Tervaert JW, Arimura Y, et al (2020). 2020 international consensus on ANCA testing beyond systemic vas-culitis. Autoimmun Rev, 19(9): 102618.
4. Yang H, Wang H, Andersson U (2020). Tar-geting Inflammation Driven by HMGB1. Front Immunol, 11:484.
5. Magna M, Pisetsky DS (2014). The role of HMGB1 in the pathogenesis of inflam-matory and autoimmune diseases. Mol Med, 20(1): 138-146.
6. Qian B, Huang H, Cheng M, et al (2020). Mechanism of HMGB1-RAGE in Kawa-saki disease with coronary artery injury. Eur J Med Res, 25(1): 8.
7. Zhu B, Li N, Zhu Q, et al (2019). Associa-tion of serum high mobility group box 1 levels with disease activity and renal in-volvement in patients with systemic vas-culitis. Medicine (Baltimore), 98(6): e14493.
8. Xu PC, Chen M, Zhao MH (2013). Antineu-trophil cytoplasmic autoantibody-associated vasculitis in Chinese patients. Clin Exp Nephrol, 17(5): 705-707.
9. Ferro F, Quartuccio L, Monti S, et al (2021). One year in review 2021: systemic vascu-litis. Clin Exp Rheumatol, 39 Suppl 129(2): 3-12.
10. Grayson PC, Monach PA, Pagnoux C, et al (2015). Vasculitis Clinical Research Con-sortium. Value of commonly measured laboratory tests as biomarkers of disease activity and predictors of relapse in eo-sinophilic granulomatosis with polyan-giitis. Rheumatology (Oxford), 54(8): 1351-1359.
11. Andersson U, Harris HE (2010). The role of HMGB1 in the pathogenesis of rheu-matic disease. Biochim Biophys Acta, 1799 (1-2): 141-148.
12. Venereau E, Casalgrandi M, Schiraldi M, et al (2012). Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release. J Exp Med, 209(9): 1519–1528.
13. Liu T, Son M, Diamond B (2020). HMGB1 in Systemic Lupus Erythematosus. Front Immunol, 11: 1057.
14. Kuo KC, Yang YL, Lo MH, et al (2021). In-creased Expression of Pyroptosis in Leukocytes of Patients with Kawasaki Disease. Diagnostics (Basel), 11(11):2035.
15. Yang M, Yang X, Wang S, et al (2019). HMGB1-induced endothelial cell pyrop-tosis is involved in systemic inflamma-tory response syndrome following ra-diofrequency ablation of hepatic he-mangiomas. Am J Transl Res, 11(12): 7555-7567.
16. Wang J, Li R, Peng Z, et al (2020). HMGB1 participates in LPS-induced acute lung injury by activating the AIM2 inflam-masome in macrophages and inducing polarization of M1 macrophages via TLR2, TLR4, and RAGE/NF-κB signal-ing pathways. Int J Mol Med, 45(1): 61-80.
17. Wang S, Zhang Y (2020). HMGB1 in in-flammation and cancer. J Hematol Oncol, 13(1): 116.
18. Wu Y, Wang Y, Gong S, et al (2020). Rus-cogenin alleviates LPSinduced pulmo-nary endothelial cell apoptosis by sup-pressing TLR4 signaling. Biomed Pharma-cother, 125: 109868.
19. Li Z, Guo J, Bi L (2020). Role of the NLRP3 inflammasome in autoimmune diseases. Biomed Pharmacother, 130: 110542.
20. Kaur I, Behl T, Bungau S, et al (2020). Ex-ploring the therapeutic promise of tar-geting HMGB1 in rheumatoid arthritis. Life Sci, 258: 118164.
21. Braza MS, van Leent MMT, Lameijer M, et al (2018). Inhibiting Inflammation with Myeloid Cell-Specific Nanobiologics Promotes Organ Transplant Acceptance. Immunity, 49(5): 819-828.e6.
22. Yang H, Ochani M, Li J, et al (2004). Revers-ing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci U S A, 101(1): 296-301.
IssueVol 52 No 11 (2023) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijph.v52i11.14038
Systemic vasculitis High mobility group box-1 Pyroptosis

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
Qin Y, Li X, Shi L, Liu Y, Wang Z, Guan Y. The Expression of High Mobility Group Box-1 (HMG1) in the Peripheral Blood and its Relation with Systemic Vasculitis Patients. Iran J Public Health. 2023;52(11):2390-2401.