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Serum HMGB-1 released by ferroptosis and necroptosis as a novel potential biomarker for systemic lupus erythematosus.
Zhao, Guowang; Wang, Xingzi; Lei, Hongtao; Ruan, Ni; Yuan, Bo; Tang, Songbiao; Ni, Nan; Zuo, Zan; Xun, Linting; Luo, Mei; Zhao, Qiuyan; Qi, Jialong; Fu, Ping.
Affiliation
  • Zhao G; Department of Rheumatology and Clinical Immunology, The Second Affiliated Hospital of Kunming Medical University, Yunnan Province, Kunming 650101, China.
  • Wang X; Department of Nephrology, Yueyang Central Hospital, Hunan Province, Yueyang 414000, China.
  • Lei H; School of Public Health, Kunming Medical University, Yunnan Province, Kunmin 650500, China.
  • Ruan N; Department of Rheumatology and Clinical Immunology, The Second Affiliated Hospital of Kunming Medical University, Yunnan Province, Kunming 650101, China.
  • Yuan B; Department of organ transplantation department, The First Affiliated Hospital of Kunming Medical University, Yunnan Province, Kunmin 650033, China.
  • Tang S; Department of Rheumatology, Yueyang Central Hospital, Hunan Province, Yueyang 414000, China.
  • Ni N; Department of Rheumatology and Clinical Immunology, The Second Affiliated Hospital of Kunming Medical University, Yunnan Province, Kunming 650101, China.
  • Zuo Z; Department of Gastroenterology, First People's Hospital of Yunnan Province, Yunnan Province, Kunming 650033, China.
  • Xun L; Department of Gastroenterology, First People's Hospital of Yunnan Province, Yunnan Province, Kunming 650033, China.
  • Luo M; Department of Gastroenterology, First People's Hospital of Yunnan Province, Yunnan Province, Kunming 650033, China.
  • Zhao Q; Department of Gastroenterology, First People's Hospital of Qujing, Yunnan Province, Qujing, China. Electronic address: zqiuyls@163.com.
  • Qi J; Department of Gastroenterology, First People's Hospital of Yunnan Province, Yunnan Province, Kunming 650033, China; Yunnan Provincial Key Laboratory of Clinical Virology, The First People's Hospital of Yunnan Province, Kunming, Yunnan,650032, China; Yunnan Provincial Key Laboratory of Birth Defects
  • Fu P; Department of Rheumatology and Clinical Immunology, The Second Affiliated Hospital of Kunming Medical University, Yunnan Province, Kunming 650101, China. Electronic address: 19100791112@163.com.
Int Immunopharmacol ; 140: 112886, 2024 Oct 25.
Article in En | MEDLINE | ID: mdl-39128419
ABSTRACT
High mobility group box proterin-1 (HMGB-1) is a multifunctional protein that can be released by various programmed cell deaths (PCDs), such as necroptosis and ferroptosis. PCDs play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). However, the role of HMGB-1 in the process of SLE remains unclear. This study aims to demonstrate the potential diagnosing role of serum HMGB-1 in SLE that released by necroptosis and ferroptosis. We found that the serum levels of HMGB-1, receptor-interacting protein kinase 3 (RIPK3) /mixed lineage kinase domain-like protein (MLKL) related with necroptosis, and metabolites associated with ferroptosis were significantly upregulated in SLE patients compared to HC individuals. These serum levels were positively correlated with SLE disease activity. Additionally, the serum level of HMGB-1 showed a strong positive correlated with the levels of RIPK3/MLKL and ferroptosis metabolites. Moreover, the serum level of HMGB-1 was correlated with renal involvement and high-antinuclear antibodies (ANA) titer. After SLE serum and interferon γ (IFN-γ) treatment in vitro, the level of necroptosis and ferroptosis markers were activated and HMGB1 was released both in HEK293 and HK2 cells. Clinically, HMGB-1 was considered as a significant independent risk factor in SLE serum by binary logistic assay. Notably, HMGB-1 exhibited outstanding diagnostic ability for SLE by the area under the curve (AUC) in receiver operating characteristic (ROC) curve analysis. Taken together, our study indicates that the serum level of HMGB-1 is a promising biomarker for the diagnosis and monitoring of SLE.
Subject(s)
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Biomarkers / HMGB1 Protein / Receptor-Interacting Protein Serine-Threonine Kinases / Ferroptosis / Necroptosis / Lupus Erythematosus, Systemic Limits: Adult / Female / Humans / Male / Middle aged Language: En Journal: Int Immunopharmacol / Int. immunopharmacol / International immunopharmacology Year: 2024 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Biomarkers / HMGB1 Protein / Receptor-Interacting Protein Serine-Threonine Kinases / Ferroptosis / Necroptosis / Lupus Erythematosus, Systemic Limits: Adult / Female / Humans / Male / Middle aged Language: En Journal: Int Immunopharmacol / Int. immunopharmacol / International immunopharmacology Year: 2024 Document type: Article