Rheumatology & Autoimmunity (Sep 2024)

GPX4 mRNA levels in the polymorphonuclear neutrophils are negatively correlated with autoantibody production, disease activity, and lupus alopecia in systemic lupus erythematosus

  • Liuying Li,
  • Fangyuan Yang,
  • Huijuan Liu,
  • Ruilin Zhang,
  • Rongmei Liang,
  • Wenchao Xu,
  • Yingfei Li,
  • Minshuang Luo,
  • Zeqing Zhai,
  • Jian Zhuang,
  • Hongyu Jie,
  • Xing Li,
  • Xingliang Shi,
  • Xinai Han,
  • Yi He,
  • Erwei Sun

DOI
https://doi.org/10.1002/rai2.12133
Journal volume & issue
Vol. 4, no. 3
pp. 165 – 173

Abstract

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Abstract Background Ferroptosis is a type of regulated necrosis and glutathione peroxidase 4 (GPX4) has been recognized as a key enzyme that protects against ferroptosis. However, the significance of GPX4 in polymorphonuclear neutrophils (PMNs) of systemic lupus erythematosus (SLE) has not been explored. So we examined GPX4 mRNA in PMNs and analyzed its association with serological and clinical features. Methods A single center research from the Department of Rheumatology and Immunology of the Third Affiliated Hospital, Southern Medical University was conducted between December 2020 and September 2022. Real‐time transcription‐polymerase chain reaction analysis was used to determine the expression of GPX4 mRNA in PMNs from patients suffering from different rheumatoid immune diseases and healthy controls. The associations of GPX4 RNA levels in SLE patients with serological and clinical indicators were assessed by Spearman's correlation analysis. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic value of GXP4 mRNA for SLE. Results GPX4 mRNA levels were lower in SLE patients than those in healthy individuals, patients with rheumatoid arthritis and axial spondyloarthritis. GPX4 mRNA levels were negatively correlated with the number of positive autoantibodies (r = −0.3072, p = 0.0300), anti‐dsDNA antibody (r = −0.3654, p = 0.0336), antinucleosome antibody (r = −0.4052, p = 0.0263), erythrocyte sedimentation rate (r = −0.3773, p = 0.0069), C‐reactive protein (r = −0.4037, p = 0.0036), and SLE disease activity index (r = −0.3072, p = 0.0300). GPX4 mRNA levels were downregulated in patients with alopecia compared with patients without alopecia (p < 0.05). The diagnostic capacity of GPX4 mRNA achieved high diagnostic accuracy (area under the curve = 0.848) with sensitivity (78.00%) and specificity (80.95%). Conclusion Downregulated GPX4 mRNA in PMNs of SLE patients is negatively associated with the production of antinuclear antibodies, disease activity, and lupus alopecia, suggesting an important role of ferroptosis in SLE, high diagnostic value of GPX4 mRNA in PMNs, and potential therapies targeting GPX4 for SLE patients, especially lupus alopecia.

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