高迁移率族蛋白1在肠道病毒71型手足口病患者中的表达及临床价值

目的:分析不同分期肠道病毒71型(EV71)手足口病(HFMD)患儿高迁移率族蛋白1(HMGB1)水平的表达变化,研究HMGB1在HFMD重症化中的临床价值及其相关作用机制。方法:将2018年5月至2019年12月西安市儿童医院感染科收治住院的EV71型HFMD患儿共130例纳入研究(研究组),其中普通型90例(轻症组)、重症40例(重症组)。以儿保科同期体检的50例健康儿童纳入对照组,采用Real time-PCR检测各组儿童外周血单核细胞HMGB1 mRNA表达水平,同时用ELISA方法检测血浆HMGB1和肿瘤坏死因子-α(TNF-α)、转化生长因子-β(TGF-β)及白细胞介素-6(IL-6)水平,比较血浆高水平HMGB1和低水平HMGB1患儿重症发生率并分析HMGB1与细胞因子肿瘤坏死因子-α(TNF-α)、转化生长因子-β(TGF-β)、白细胞介素-6(IL-6)间的相关性。结果:HFMD轻症组和重症组患儿和对照组HMGB1 mRNA表达水平和血浆HMGB1含量差异有统计学意义(F=54.629、P<0.001,F=127.924、P<0.001)。受试者工作特征曲线提示,当HMGB1为13090 pg/ml时约登指数最大,对应的敏感度和特异度分别为80.9%和73.5%。高HMGB1患儿重症发生率(44.6%、33/74)显著高于低HMGB1患儿(12.5%、7/56),差异有统计学意义(χ^(2)=26.986、P<0.001)。三组研究对象TNF-α(F=11.284、P<0.001)、TGF-β(F=57.346、P<0.001)及IL-6(F=45.362、P<0.001)差异均有统计学意义,重症组较轻症组患儿升高更为显著(TNF-α:t=7.503、P=0.035;TGF-β:t=9.307、P=0.017;IL-6:t=25.618、P<0.001)。入组HFMD患儿血浆中HMGB1含量与TNF-α、TGF-β及IL-6水平均呈正相关(r=0.642、0.775、0.825,P均<0.001)。结论:HFMD患儿HMGB1水平升高,以重症患儿HMGB1水平升高更显著;HMGB1可能通过调控IL-6、TGF-β和TNF-α等细胞因子参与手足口病重症的发生、发展过程。

Expression and clinical value of high mobility group protein 1 in patients with enterovirus 71 related hand,foot and mouth disease

ObjectiveTo investigate the expression changes of high mobility group protein 1 (HMGB1) in children with different stages of enterovirus 71 (EV71) related hand, foot and mouth disease (HFMD), and to analyze the clinical value and mechanism of HMGB1 in the severity of HFMD. MethodsTotal of 130 cases of EV71 HFMD admitted to the Department of infection of Xi’an Children’s Hospital from May 2018 to December 2019 were enrolled in study group, including 90 mild cases (mild group) and 40 severe cases (severe group). While a total of 50 healthy children who had medical check-up in Child Health Unit in the same period were selected as the control group. Real time PCR was used to detect the expression of HMGB1 mRNA in peripheral blood mononuclear cells in each group. ELISA was used to detect the plasma levels of HMGB1, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β) and interleukin-6 (IL-6). The incidence of severity in children with high plasma level of HMGB1 and low level of HMGB1 was compared, and the correlation between HMGB1 and cytokines TNF-α, TGF-β and IL-? were analyzed, respectively. ResultsThe expression of HMGB1 mRNA and the content of plasma HMGB1 were significantly different among cases in mild group, severe group and control group (F = 54.629, P < 0.001; F = 127.924, P < 0.001). The receiver operating characteristic curve (ROC) showed that when HMGB1 was 13 090 pg/ml, the Youden index was the highest, the sensitivity was 80.9%, and the specificity was 73.5%. The incidence of severe cases in children with high HMGB1 (44.6%, 33/74) was significantly lower than that of children with low HMGB1 (12.5%, 7/56), with significant difference (χ² = 26.986, P < 0.001). The levels of TNF-α (F = 11.284, P < 0.001), TGF-β (F = 57.346, P < 0.001) and IL-? (F = 45.362, P < 0.001) among the three groups were all significantly different, especially in severe group (TNF-α: severe group vs. mild group: t = 7.503, P = 0.035; TGF-β: severe group vs. mild group: t = 9.307, P = 0.017; IL-6: severe group vs. mild group: t = 25.618, P < 0.001). The level of plasma HMGB1 of children with HFMD was positively correlated with the levels of TNF-α, TGF-β and IL-? (r = 0.642, 0.775, 0.825; all P < 0.001). ConclusionsHMGB1 level were increased in children with EV71 HFMD, especially in severe cases; HMGB1 may participate in the occurrence and development of severe HFMD by regulating cytokines such as IL-6, TGF-β and TNF-α.