[系统性红斑狼疮患者外周血单个核细胞中微管相关蛋白1轻链3相关蛋白-1（LC3）mRNA的表达及意义]

[The expression and significance of microtubule-associated protein 1 light chain 3-related protein-1 (LC3) mRNA in peripheral blood mononuclear cells in patients with systemic lupus erythematosus].

作者信息

Luo Xiongyan, Yang Minghui, Xia Yanhui, Xiang Yang, Liu Yi, Yuan Guohua

机构信息

Department of Rheumatology and Immunology, West China Hospital, Sichuan University, Chengdu 610041, China. Email:

出版信息

Zhonghua Nei Ke Za Zhi. 2015 Feb;54(2):134-8.

PMID:25907845

Abstract

OBJECTIVE

Increasing evidence supports the involvement of autophagy in the etiopathology of autoimmune diseases. Systemic lupus erythematosus (SLE) is a potentially fatal autoimmune disease characterized by production of multiple autoantibodies through poorly understood mechanism. In order to explore the role of autophagy in the development of SLE, the expression of autophagy related gene microtubule-associated protein 1 light chain 3 (MAPLC3) in peripheral blood mononuclear cells (PBMCs) was measured in patients with SLE.

METHODS

The mRNA levels of LC3 in PBMCs from 56 SLE patients and 45 healthy individuals were detected by real-time quantitative polymerase chain reaction (qPCR) technique. Autophagy in PBMCs was also determined by flow cytometry (FACs) in 20 SLE patients and 15 healthy controls. The correlation between LC3 mRNA expression and disease activity of SLE (SLEDAI) was then analyzed.

RESULTS

The mRNA level of LC3 (RQ) in SLE patients was obviously downregulated compared with that in healthy population (1.30 ± 0.10 vs 1.35 ± 0.09; P = 0.029), paralleled with the decreased autophagy rate detected by flow cytometry in PBMCs of SLE patients [(2.21 ± 1.07) % vs (9.91 ± 4.01) %;P = 0.047]. Moreover, LC3 mRNA expression level was negatively correlated with SLEDAI (r = -0.337, P = 0.023). However, when the clinical features of 27 SLE patients with decreased LC3 mRNA expression (RQ<1.351) were compared with those of other 29 SLE patients with normal or high LC3 mRNA expression (RQ>1.351), increasing rates of arthritis, serositis, hematological abnormalities were noted in patients with decreased LC3 mRNA expression yet without statistically significance. However, there was a significant difference between two groups in the incidence of renal involvement (P = 0.028).

CONCLUSION

The impaired autophagy due to downregulated LC3 mRNA level in SLE patients indicates that autophagy plays a role in mediating the occurrence and development of SLE.

摘要

目的

越来越多的证据支持自噬参与自身免疫性疾病的病因病理过程。系统性红斑狼疮（SLE）是一种潜在致命的自身免疫性疾病，其特征是通过尚不清楚的机制产生多种自身抗体。为了探究自噬在SLE发病中的作用，我们检测了SLE患者外周血单个核细胞（PBMCs）中自噬相关基因微管相关蛋白1轻链3（MAPLC3）的表达。

方法

采用实时定量聚合酶链反应（qPCR）技术检测56例SLE患者和45例健康个体PBMCs中LC3的mRNA水平。同时采用流式细胞术（FACs）检测20例SLE患者和15例健康对照者PBMCs中的自噬情况。然后分析LC3 mRNA表达与SLE疾病活动度（SLEDAI）之间的相关性。

结果

与健康人群相比，SLE患者中LC3的mRNA水平（RQ）明显下调（1.30±0.10 vs 1.35±0.09；P = 0.029），这与流式细胞术检测到的SLE患者PBMCs中自噬率降低情况相平行[（2.21±1.07）% vs（9.91±4.01）%；P = 0.047]。此外，LC3 mRNA表达水平与SLEDAI呈负相关（r = -0.337，P = 0.023）。然而，当比较27例LC3 mRNA表达降低（RQ<1.351）的SLE患者与其他29例LC3 mRNA表达正常或升高（RQ>1.351）的SLE患者的临床特征时，发现LC3 mRNA表达降低的患者关节炎、浆膜炎、血液学异常的发生率增加，但无统计学意义。然而，两组在肾脏受累发生率方面存在显著差异（P = 0.028）。