Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement, and SLE disease activity.
Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement, and SLE disease activity.
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PBMC 中 MLKL mRNA 水平升高与自身抗体产生、肾脏受累和 SLE 疾病活动相关
DOI：
10.1186/s13075-020-02332-7
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发表时间：
2020-10-14
影响因子：
4.9
通讯作者：
Sun E
中科院分区：
文献类型：
--
作者：
Zhang M;Jie H;Wu Y;Han X;Li X;He Y;Shi X;Luo Y;Sun Y;Yang J;Yang J;Quan S;Lao X;Tan L;Sun E
背景坏死性凋亡是一种调节性坏死，与多种自身免疫性疾病有关。混合谱系激酶结构域样假激酶（MLKL）已被确定为坏死性凋亡的关键执行者；然而，MLKL 在系统性红斑狼疮 (SLE) 外周血单核细胞 (PBMC) 中的意义尚未得到研究。在本研究中，我们旨在测定PBMC中MLKL的mRNA水平，并检查其与SLE临床特征和血清学参数的关系。方法采用实时转录聚合酶链反应（RT-PCR）分析测定59例SLE患者、25例类风湿性关节炎（RA）患者和30例年龄和性别匹配的健康对照（HC）的PBMC中MLKL mRNA的表达。进行 Spearman 相关性检验以评估 MLKL mRNA 与临床变量的相关性。创建受试者工作特征（ROC）曲线来评估诊断价值。结果我们的结果显示，与 RA 和 HC 个体相比，SLE 患者 PBMC 中的 MLKL mRNA 上调。抗核抗体阳性的 SLE 患者的 MLKL mRNA 显着高于抗体阴性患者。在 SLE 患者中，与无狼疮性肾炎 (LN) 的患者相比，MLKL mRNA 在活动性患者中的表达量也高于稳定患者。 MLKL mRNA水平与c反应蛋白（CRP）（r= 0.3577，p= 0.0237）、红细胞沉降率（ESR）（r= 0.4091，p= 0.0043）、血清免疫球蛋白G（IgG）浓度呈显着正相关。 （r= 0.3546，p= 0.0289），以及阳性抗核抗体（ANA）的数量（r= 0.3945，p= 0.0432）。 ROC 分析显示，PBMC 中的 MLKL mRNA 曲线下面积为 0.9277（95% CI 0.8779–0.9775，p< 0.001），可区分 SLE 和对照。结论这些结果表明，SLE 患者 PBMC 中 MLKL mRNA 水平升高与肾脏受累和疾病活动度相关，从而确定了可能受益的 SLE 或 LN 患者亚组。来自针对 MLKL 的早期诊断和治疗。
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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影响因子：
30.5
作者：
Scharer, Christopher D.;Blalock, Emily L.;Boss, Jeremy M.
通讯作者：
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影响因子：
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Paludan SR;Bowie AG
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通讯作者：
Kumanogoh A
影响因子：
33.7
作者：
Olsen, Nancy J.;Karp, David R.
通讯作者：
Karp, David R.