ArticleArthritis research & therapy2020
Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement, and SLE disease activity.
Article in Arthritis research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 19 citations in OpenAlex.
- Necroptosis and the RIPK1-RIPK3-MLKL pathway in chronic kidney disease: mechanisms, crosstalk, and therapeutic opportunities.Renal failure · 2026Review
- Autophagy determines the fate of immune cells by regulating metabolic remodeling and PANoptosis (Review).International journal of molecular medicine · 2026Review
- Targeting RIPK1 is a promising therapeutic avenue for systemic lupus erythematosus.Clinical rheumatology · 2026Article
- Identification and validation of necroptosis-related genes in peripheral blood mononuclear cells of Sjögren disease.Frontiers in medicine · 2026Article
- Imbalance of programmed cell death patterns mediated by dendritic cell subsets in systemic lupus erythematosus and lupus nephritis.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Article
- Pathological mechanisms and crosstalk among various cell death pathways in cardiac involvement of systemic lupus erythematosus.Frontiers in immunology · 2024Review
- PANoptosis in autoimmune diseases interplay between apoptosis, necrosis, and pyroptosis.Frontiers in immunology · 2024Review
- PANoptosis: Mechanism and Role in Pulmonary Diseases.International journal of molecular sciences · 2023Review
- Upregulation of necroptosis markers RIPK3/MLKL and their crosstalk with autophagy-related protein Beclin-1 in primary immune thrombocytopenia.Clinical and experimental medicine · 2023Article
- Distinct binding mode of BAFF antagonist antibodies belimumab and tabalumab, analyzed by computer simulation.Journal of molecular modeling · 2022Article
- Emerging Molecular Markers Towards Potential Diagnostic Panels for Lupus.Frontiers in immunology · 2021Review
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Authors and funding
15 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundNecroptosis 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.
methodsReal-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.
resultsOur 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.
conclusionsThese 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.
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