Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement, and SLE disease activity

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

doi:10.1186/s13075-020-02332-7

Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement, and SLE disease activity

Arthritis Res Ther. 2020 Oct 14;22(1):239. doi: 10.1186/s13075-020-02332-7.

Authors

Mingjiao Zhang^{1

2}, Hongyu Jie^{1

2}, Yong Wu³, Xinai Han^{1

2}, Xing Li^{1

2}, Yi He^{1

2}, Xingliang Shi^{1

2}, Yuwei Luo^{1

2}, Ying Sun^{1

2}, Jinlong Yang^{1

2}, Jing Yang^{1

2}, Shulv Quan^{1

2}, Xiaobin Lao^{1

2}, Liping Tan^{1

2}, Erwei Sun^{4

5

6}

Affiliations

¹ Department of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
² Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China.
³ Clinical Medical Laboratory Center, The First Affiliated Hospital, Jinan University, Guangzhou, China.
⁴ Department of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China. sunew@smu.edu.cn.
⁵ Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital, Southern Medical University, Guangzhou, China. sunew@smu.edu.cn.
⁶ Department of Rheumatology and Immunology, Shunde Hospital, Southern Medical University, Guangzhou, China. sunew@smu.edu.cn.

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.

Keywords: Diagnosis; MLKL; Necroptosis; PBMCs; SLE; mRNA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Antinuclear
Humans
Leukocytes, Mononuclear
Lupus Erythematosus, Systemic* / genetics
Lupus Nephritis* / genetics
Protein Kinases
RNA, Messenger / genetics

Substances

Antibodies, Antinuclear
RNA, Messenger
MLKL protein, human
Protein Kinases