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Ferroptosis in peripheral blood mononuclear cells of systemic lupus erythematosus
Kang Tao1, Yuan Tian1, Shifei Li1
1Department of Dermatology, the First Affiliated Hospital, Army Medical University, Chongqing, China.
Objectives:
To investigate the evidence of ferroptosis in peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE).
Methods:
PBMCs were collected from 30 patients diagnosed as SLE and without any standardised treatment previously and 10 healthy controls. Meanwhile the clinical and laboratory data were collected. The intracellular Fe2+, reactive oxygen species (ROS) and lipid peroxidation (LPO) were detected by fluorescence probe and flow cytometry. The morphology of cells and intracellular organelles were observed by transmission electron microscopy. RT-qPCR and Western blot were applied to compare the expression of GPX4 in PBMCs.
Results:
The concentration of Fe2+, levels of ROS and LPO in PBMCs from SLE patients were significantly higher than those in healthy controls (p<0.05), and significant differences between the two groups were observed in CD14+ monocytes, CD19+B cells, and CD56+ NK cells respectively. The more prominent differences were observed in SLE patients with renal involvement, liver injury and higher disease activity score. There was no significant difference in GPX4 mRNA expression between SLE patients and healthy controls, however GPX4 protein expression was significantly lower in SLE patients compared to healthy controls, with a negative correlation with the SLE disease activity index. Transmission electron microscopy revealed typical morphological features of ferroptosis such as decreased mitochondrial volume, increased mitochondrial membrane density, and disappearance of mitochondrial cristas.
Conclusions:
Ferroptosis occurred more frequently in PBMCs of SLE patients than healthy controls, including CD14+ monocytes, CD19+B cells, CD56+ NK cells, and so on, with negative association with SLE disease activity, which indicated the correlation between ferroptosis with the pathogenesis of SLE.
Insights
Ferroptosis, a form of cell death, is evident in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE). This finding suggests ferroptosis plays a role in SLE pathogenesis.
Area of Science:
- Immunology
- Cell Biology
- Pathology
Background:
- Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with complex pathogenesis.
- Peripheral blood mononuclear cells (PBMCs) are crucial immune cells involved in autoimmune responses.
Purpose of the Study:
- To investigate the presence and characteristics of ferroptosis in PBMCs from SLE patients.
- To explore the correlation between ferroptosis markers and SLE disease activity.
Main Methods:
- Collected PBMCs from 30 SLE patients and 10 healthy controls.
- Assessed intracellular iron (Fe2+), reactive oxygen species (ROS), and lipid peroxidation (LPO) using fluorescence probes and flow cytometry.
- Analyzed GPX4 expression (mRNA and protein) via RT-qPCR and Western blot, and observed cellular morphology using transmission electron microscopy.
Main Results:
- SLE patients exhibited significantly higher Fe2+, ROS, and LPO levels in PBMCs compared to controls.
- GPX4 protein expression was significantly lower in SLE patients' PBMCs and negatively correlated with disease activity.
- Transmission electron microscopy revealed characteristic ferroptosis-associated mitochondrial changes in SLE PBMCs.
Conclusions:
- Ferroptosis is present in PBMCs of SLE patients, affecting various immune cell subsets.
- The findings indicate a significant association between ferroptosis and the pathogenesis of SLE.
