Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement, and SLE disease activity
Abstract 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)...
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| Format: | Article |
| Language: | English |
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BMC
2020-10-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13075-020-02332-7 |
| _version_ | 1828833863770570752 |
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| author | Mingjiao Zhang Hongyu Jie Yong Wu Xinai Han Xing Li Yi He Xingliang Shi Yuwei Luo Ying Sun Jinlong Yang Jing Yang Shulv Quan Xiaobin Lao Liping Tan Erwei Sun |
| author_facet | Mingjiao Zhang Hongyu Jie Yong Wu Xinai Han Xing Li Yi He Xingliang Shi Yuwei Luo Ying Sun Jinlong Yang Jing Yang Shulv Quan Xiaobin Lao Liping Tan Erwei Sun |
| author_sort | Mingjiao Zhang |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-12T17:28:32Z |
| format | Article |
| id | doaj.art-d5da6a9dff1a4aea9a10382811e15c2e |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-12-12T17:28:32Z |
| publishDate | 2020-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-d5da6a9dff1a4aea9a10382811e15c2e2022-12-22T00:17:27ZengBMCArthritis Research & Therapy1478-63622020-10-012211810.1186/s13075-020-02332-7Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement, and SLE disease activityMingjiao Zhang0Hongyu Jie1Yong Wu2Xinai Han3Xing Li4Yi He5Xingliang Shi6Yuwei Luo7Ying Sun8Jinlong Yang9Jing Yang10Shulv Quan11Xiaobin Lao12Liping Tan13Erwei Sun14Department of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical UniversityDepartment of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical UniversityClinical Medical Laboratory Center, The First Affiliated Hospital, Jinan UniversityDepartment of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical UniversityDepartment of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical UniversityDepartment of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical UniversityDepartment of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical UniversityDepartment of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical UniversityDepartment of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical UniversityDepartment of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical UniversityDepartment of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical UniversityDepartment of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical UniversityDepartment of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical UniversityDepartment of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical UniversityDepartment of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical UniversityAbstract 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.http://link.springer.com/article/10.1186/s13075-020-02332-7SLENecroptosisMLKLmRNAPBMCsDiagnosis |
| spellingShingle | Mingjiao Zhang Hongyu Jie Yong Wu Xinai Han Xing Li Yi He Xingliang Shi Yuwei Luo Ying Sun Jinlong Yang Jing Yang Shulv Quan Xiaobin Lao Liping Tan Erwei Sun Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement, and SLE disease activity Arthritis Research & Therapy SLE Necroptosis MLKL mRNA PBMCs Diagnosis |
| title | Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement, and SLE disease activity |
| title_full | Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement, and SLE disease activity |
| title_fullStr | Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement, and SLE disease activity |
| title_full_unstemmed | Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement, and SLE disease activity |
| title_short | Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement, and SLE disease activity |
| title_sort | increased mlkl mrna level in the pbmcs is correlated with autoantibody production renal involvement and sle disease activity |
| topic | SLE Necroptosis MLKL mRNA PBMCs Diagnosis |
| url | http://link.springer.com/article/10.1186/s13075-020-02332-7 |
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