Huang Xiaolan, Su Gaixiu, Wang Zhen, Shangguan Shaofang, Cui Xiaodai, Zhu Jia, Kang Min, Li Shengnan, Zhang Ting, Wu Fengqi, Wang Li
Central Laboratory for Clinical Research, Capital Institute of Pediatrics, Beijing, China.
Int J Rheum Dis. 2014 Mar;17(3):280-90. doi: 10.1111/1756-185X.12239. Epub 2013 Dec 11.
Methylation abnormalities in T lymphocytes have been reported to correlate with systemic lupus erythematosus (SLE). Previous studies identified hypomethylation in the promoter of several genes linked to SLE. Long interspersed nucleotide element-1 (LINE-1) constitutes 17-25% of the human genome, and LINE-1 hypomethylation has been reported in SLE. Limited information is available regarding LINE-1 methylation in juvenile SLE (JSLE).
Methylation levels of LINE-1 in peripheral blood mononuclear cells (PBMCs) from 59 JSLE and 47 control samples were examined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Total homocysteine (tHcy) concentrations in plasma were measured by immunoassay.
Significant hypomethylation of LINE-1 was observed in PBMCs from JSLE patients (60.93% in cases compared with 62.88% in controls, P = 0.001). Significant LINE-1 hypomethylation was observed in active SLE compared to controls (60.66% vs. 62.88%, P = 0.001). According to other clinical parameters, a significant correlation was found between LINE-1 methylation levels and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2000) of the cases (r = -0.285, P = 0.032). The risk of JSLE increased with decreasing levels of LINE-1 methylation, with an odds ratio of 14.5 (95% CI: 2.8-75.6, P = 0.002). Cases had significantly higher plasma concentrations of tHcy than controls (15.11 vs. 11.02 μmol/L, P = 0.028); the correlation between LINE-1 methylation levels and tHcy was significant (r = -0.4, P = 0.013). Correlations between methylation levels of LINE-1 and complement component 3 were significant (r = 0.317, P = 0.044; r = 0.387, P = 0.031, in total JSLE and active JSLE, respectively).
Hypomethylation of LINE-1 is associated with risk of JSLE, and LINE-1 methylation levels were related to disease activity and clinical manifestations. The correlation between tHcy levels and LINE-1 methylation was significant.
据报道，T淋巴细胞中的甲基化异常与系统性红斑狼疮（SLE）相关。先前的研究发现与SLE相关的几个基因启动子存在低甲基化。长散在核元件1（LINE-1）占人类基因组的17%-25%，且在SLE中已报道存在LINE-1低甲基化。关于青少年SLE（JSLE）中LINE-1甲基化的信息有限。
采用基质辅助激光解吸/电离飞行时间质谱法检测59例JSLE患者和47例对照样本外周血单个核细胞（PBMC）中LINE-1的甲基化水平。采用免疫分析法测定血浆中总同型半胱氨酸（tHcy）浓度。
观察到JSLE患者PBMC中LINE-1显著低甲基化（病例组为60.93%，对照组为62.88%，P = 0.001）。与对照组相比，活动期SLE中观察到显著的LINE-1低甲基化（60.66%对62.88%，P = 0.001）。根据其他临床参数，发现病例组中LINE-1甲基化水平与系统性红斑狼疮疾病活动指数2000（SLEDAI-2000）之间存在显著相关性（r = -0.285，P = 0.032）。JSLE的风险随着LINE-1甲基化水平的降低而增加，优势比为14.5（95%CI：2.8-75.6，P = 0.002）。病例组血浆tHcy浓度显著高于对照组（15.11对11.02μmol/L，P = 0.028）；LINE-1甲基化水平与tHcy之间的相关性显著（r = -0.4，P = 0.013）。LINE-1甲基化水平与补体成分3之间的相关性显著（分别在总JSLE组和活动期JSLE组中，r = 0.317，P = 0.044；r = 0.387，P = 0.031）。
LINE-1低甲基化与JSLE风险相关，且LINE-1甲基化水平与疾病活动和临床表现有关。tHcy水平与LINE-1甲基化之间的相关性显著。
