GPX4 mRNA levels in the PMNs are negatively correlated with autoantibody production, disease activity and lupus alopecia in SLE

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Abstract Background: Ferroptosis is a recently discovered 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 inPolymorphonuclear neutrophils (PMNs) ofsystemic lupus erythematosus (SLE) has not been explored. In this study, we examined GPX4 mRNA in PMNs and analyzed its association with serological and clinical features. Methods: Real-time transcription-polymerase chain reaction (RT-PCR)analysis was used to determine the expression of GPX4 mRNA in PMNs from 50 SLE patients, 49 RA patients, 39 axSpA patients and 42 healthy controls(HC). The associations of the relative RNA expression levels of GPX4 with serological and clinical indicators were assessed by Spearman's correlation analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of GXP4 mRNA for SLE. Results: GPX4 mRNA levels was lower in SLE patients than those in healthy individuals, rheumatoid arthritis(RA) patients and axial spondyloarthritis (axSpA) patients. GPX4 mRNA levels were negatively correlated with the numbers of positive antinuclear antibodies (ANAs) (r=-0.3072, p=0.0300), anti-dsDNA antibody (r=-0.3654, p=0.0336) and antinucleosome antibody (ANuA)(r=-0.4052, p=0.0263). GPX4 mRNA levels were also negatively correlated with erythrocyte sedimentation rate(ESR) (r=-0.3773, p=0.0069), C-reactive protein(CRP) (r=-0.4037, p=0.0036) and SLE Disease Activity Index(SLEDAI) score(r=-0.3072, p=0.0300). Interestingly, GPX4 mRNA levels were downregulated in patients with alopecia compared with patients without alopecia. The diagnostic capacity of GPX4 mRNA achieved high diagnostic accuracy (the area under the curve, AUC: 0.8483) with sensitivity (78.00%) and specificity (80.95%). Conclusions: These results showed that downregulated GPX4 mRNA in PMNs of SLE patients is negatively associated with production of ANAs, 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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