免疫相关 miRNAs 与混合性结缔组织病的相关性研究。
Association study between immune-related miRNAs and mixed connective tissue disease.
机构信息
Department of Molecular Biology, National Institute of Geriatrics, Rheumatology, and Rehabilitation, Spartańska 1, 02-637, Warsaw, Poland.
Department of Connective Tissue Diseases, National Institute of Geriatrics, Rheumatology, and Rehabilitation, Spartanska 1, Warsaw, 02-637, Poland.
出版信息
Arthritis Res Ther. 2021 Jan 11;23(1):19. doi: 10.1186/s13075-020-02403-9.
BACKGROUND
Mixed connective tissue disease (MCTD) is a rare condition that is distinguished by the presence of specific U1-RNP antibodies. Information about its etiopathology and diagnostics is still unclear. miRNAs such as miR-146, miR-155, and miR-143 emerged as key regulators of the immune system, known to be involved in the development of autoimmune diseases and cancers. We performed an association study between immune-related miRNAs and MCTD severity and susceptibility.
METHODS
A total of 169 MCTD patients and 575 healthy subjects were recruited to the case-control study. The miRNA polymorphisms were genotyped using TaqMan SNP genotyping assay. TNF-α, IL-6, and IFN-γ levels in serum were determined using ELISA. qRT-PCR of TRAF6, IRAK1, and microRNAs was performed using Taqman miRNA assays and TaqMan Gene Expression Assays.
RESULTS
miR-146a rs2910164 G allele and GG genotype as well as miR-143 rs713147 A allele were more frequent in healthy subjects than in MCTD patients. miR-146a rs2910164 CC genotype and miR-143 T-rs353299T-rs353291T-rs713147G-rs353298 and C-rs353299C-rs353291T-rs713147A-rs353298 haplotypes were associated with MCTD susceptibility. miR-146a rs2910164 C/T was associated with scleroderma and lymphadenopathy. miR-143 rs353299 C/T was associated with swollen fingers or hands, the presence of enlarged lymph nodes, and pericarditis/pleuritis. miR-143 rs353298 A/G was associated with the occurrence of pericarditis/pleuritis and scleroderma. miR-143 rs353291 T/C showed association with pericarditis/pleuritis. The serum TNF-α, IFN-γ, and IL-6 levels were significantly higher in MCTD patients compared to healthy subjects. miR-143 SNPs were associated with higher proinflammatory cytokine concentration in serum only in healthy controls. IRAK1 and TRAF6 expression were higher in the MCTD patients compared to controls.
CONCLUSIONS
The results of our case-control study indicate the possible significance of miR-146a and miR-143/145 in the susceptibility and clinical picture of MCTD.
背景
混合性结缔组织病（MCTD）是一种罕见的疾病，其特征是存在特定的 U1-RNP 抗体。关于其病因病理学和诊断的信息仍不清楚。miRNA 如 miR-146、miR-155 和 miR-143 已成为免疫系统的关键调节剂，已知它们参与自身免疫性疾病和癌症的发展。我们进行了一项关于免疫相关 miRNA 与 MCTD 严重程度和易感性的关联研究。
方法
共有 169 名 MCTD 患者和 575 名健康受试者纳入病例对照研究。使用 TaqMan SNP 基因分型检测试剂盒对 miRNA 多态性进行基因分型。采用 ELISA 法检测血清中 TNF-α、IL-6 和 IFN-γ 的水平。采用 Taqman miRNA 检测试剂盒和 TaqMan 基因表达检测试剂盒对 TRAF6、IRAK1 和 microRNAs 进行 qRT-PCR。
结果
miR-146a rs2910164 G 等位基因和 GG 基因型以及 miR-143 rs713147 A 等位基因在健康受试者中比 MCTD 患者更为常见。miR-146a rs2910164 CC 基因型和 miR-143 T-rs353299T-rs353291T-rs713147G-rs353298C-rs353299C-rs353291T-rs713147*A-rs353298 单倍型与 MCTD 易感性相关。miR-146a rs2910164 C/T 与硬皮病和淋巴结病有关。miR-143 rs353299 C/T 与手指或手部肿胀、淋巴结肿大、心包炎/胸膜炎有关。miR-143 rs353298 A/G 与心包炎/胸膜炎和硬皮病的发生有关。miR-143 rs353291 T/C 与心包炎/胸膜炎有关。与健康对照组相比，MCTD 患者的血清 TNF-α、IFN-γ 和 IL-6 水平明显升高。仅在健康对照组中，miR-143SNP 与血清中促炎细胞因子浓度升高有关。与对照组相比，MCTD 患者 IRAK1 和 TRAF6 的表达更高。
结论
本病例对照研究的结果表明，miR-146a 和 miR-143/145 可能在 MCTD 的易感性和临床表现中具有重要意义。
Zotero 插件