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Updated: Dec 5, 2025
The bm12 Inducible Model of Systemic Lupus Erythematosus SLE in C57BL/6 Mice
Published on: November 1, 2015
Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement, and SLE disease
Mingjiao Zhang1,2, Hongyu Jie1,2, Yong Wu3
1Department of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
Background:
Necroptosis is a form of regulated necrosis that is involved in various autoimmune diseases. Mixed lineage kinase domain-like pseudokinase (MLKL) has been identified as a key executor of necroptosis; however, the significance of MLKL in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) has not been investigated. In this study, we aimed to determine the mRNA level of MLKL in PBMCs and examine its relationship with clinical features and serological parameters in SLE.
Methods:
Real-time transcription-polymerase chain reaction (RT-PCR) analysis was used to determine the expression of MLKL mRNA in PBMCs from 59 patients with SLE, 25 patients with rheumatoid arthritis (RA), and 30 age- and sex-matched healthy controls (HC). Spearman's correlation test was performed to assess the correlation of MLKL mRNA with clinical variables. The receiver operating characteristic (ROC) curve was created to evaluate the diagnostic value.
Results:
Our results showed MLKL mRNA in PBMCs was upregulated in SLE patients compared to that in RA and HC individuals. SLE patients positive for antinuclear antibodies had significantly higher MLKL mRNA than antibody-negative patients. In SLE patients, MLKL mRNA was found to be upregulated in patients with lupus nephritis (LN) as compared with patients without LN, and also higher in active patients than in stable patients. MLKL mRNA level was significantly and positively correlated with c-reaction protein (CRP) (r = 0.3577, p = 0.0237), erythrocyte sedimentation rate (ESR) (r = 0.4091, p = 0.0043), serum immunoglobulin G (IgG) concentration (r = 0.3546, p = 0.0289), and the numbers of positive antinuclear antibodies (ANAs) (r = 0.3945, p = 0.0432). ROC analysis showed that MLKL mRNA in PBMCs had an area under the curve of 0.9277 (95% CI 0.8779-0.9775, p < 0.001) to discriminate SLE from controls.
Conclusions:
These results suggest that increased MLKL mRNA level in the PBMCs of SLE patients is correlated with renal involvement and disease activity, identifying a subgroup of patients with SLE or LN who may benefit from early diagnosis and therapies targeting MLKL.
Insights
Increased MLKL mRNA in PBMCs is linked to systemic lupus erythematosus (SLE) severity and activity. This finding may help identify SLE patients who could benefit from targeted therapies.
Area of Science:
- Immunology
- Molecular Biology
- Pathology
Background:
- Necroptosis, a regulated necrosis form, is implicated in autoimmune diseases.
- Mixed lineage kinase domain-like pseudokinase (MLKL) is a key necroptosis executor.
- The role of MLKL in peripheral blood mononuclear cells (PBMCs) in systemic lupus erythematosus (SLE) remains unexplored.
Purpose of the Study:
- To determine MLKL mRNA levels in PBMCs from SLE patients.
- To investigate the correlation between MLKL mRNA levels and clinical/serological parameters in SLE.
- To evaluate the diagnostic potential of MLKL mRNA in SLE.
Main Methods:
- Real-time RT-PCR was used to quantify MLKL mRNA in PBMCs from SLE patients, rheumatoid arthritis patients, and healthy controls.
- Spearman's correlation analysis examined associations between MLKL mRNA and clinical variables.
- Receiver operating characteristic (ROC) curve analysis assessed diagnostic accuracy.
Main Results:
- MLKL mRNA was significantly upregulated in SLE patients compared to rheumatoid arthritis patients and healthy controls.
- Higher MLKL mRNA levels correlated with positive antinuclear antibodies, lupus nephritis, and active disease.
- MLKL mRNA levels positively correlated with C-reactive protein, erythrocyte sedimentation rate, serum IgG, and ANA positivity.
- ROC analysis indicated MLKL mRNA has strong diagnostic value for discriminating SLE from controls (AUC = 0.9277).
Conclusions:
- Elevated MLKL mRNA in PBMCs of SLE patients is associated with disease activity and renal involvement.
- MLKL mRNA may serve as a biomarker for identifying SLE patients with specific clinical manifestations.
- Targeting MLKL could offer therapeutic potential for a subgroup of SLE and lupus nephritis patients.
