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

doi:10.3877/cma.j.issn.1674-1358.2022.01.002

Abstract

Abstract:

Objective

To 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.

Methods

Total 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.

Results

The 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).

Conclusions

HMGB1 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.

Key words: Hand, foot and mouth disease, High mobility group protein 1, Cytokines, Clinical value

Yufeng Zhang, Han Wan, Huafeng Fan, Juan Yuan, Ruiqing Liu, Pengfei Xu, Jun Wang, Huiling Deng. Expression and clinical value of high mobility group protein 1 in patients with enterovirus 71 related hand, foot and mouth disease[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2022, 16(01): 9-15.

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References 26

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组别	例数	HMGB1 mRNA	HMGB1（pg/ml）
重症组	40	28.53 ± 2.46	15 759.39 ± 2 419.28
轻症组	90	16.89 ± 2.53	11 598.89 ± 2 199.37
对照组	50	5.76 ± 1.27	10 116.41 ± 2 435.59
F值		54.629	127.924
P值		< 0.001	< 0.001

组别	例数	HMGB1 mRNA	HMGB1（pg/ml）
重症组	40	28.53 ± 2.46	15 759.39 ± 2 419.28
轻症组	90	16.89 ± 2.53	11 598.89 ± 2 199.37
对照组	50	5.76 ± 1.27	10 116.41 ± 2 435.59
F值		54.629	127.924
P值		< 0.001	< 0.001

组别	例数	TNF-α	TGF-β	IL-6
重症组	50	29.56 ± 9.58	259.41 ± 31.58	65.27 ± 11.57
轻症组	100	25.69 ± 10.97	229.48 ± 21.64	28.26 ± 10.74
对照组	50	21.30 ± 8.69	44.36 ± 16.32	14.32 ± 2.97
F值		11.284	57.346	45.362
P值		< 0.001	< 0.001	< 0.001

组别	例数	TNF-α	TGF-β	IL-6
重症组	50	29.56 ± 9.58	259.41 ± 31.58	65.27 ± 11.57
轻症组	100	25.69 ± 10.97	229.48 ± 21.64	28.26 ± 10.74
对照组	50	21.30 ± 8.69	44.36 ± 16.32	14.32 ± 2.97
F值		11.284	57.346	45.362
P值		< 0.001	< 0.001	< 0.001

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