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

Abstract

AbstractBackgroundFerroptosis 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.MethodsA 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.ResultsGPX4 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%).ConclusionDownregulated 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.