Systemic release of high mobility group box 1 (HMGB1) protein is associated with severe and fatal Plasmodium falciparum malaria.
Systemic release of high mobility group box 1 (HMGB1) protein is associated with severe and fatal Plasmodium falciparum malaria.
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DOI：
10.1186/1475-2875-12-105
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发表时间：
2013-03-19
期刊：
影响因子：
3
通讯作者：
Liles WC
中科院分区：
文献类型：
--
作者：
Higgins SJ;Xing K;Kim H;Kain DC;Wang F;Dhabangi A;Musoke C;Cserti-Gazdewich CM;Tracey KJ;Kain KC;Liles WC
严重恶性疟疾(SM)的发病机制部分归因于对感染的有害的全身炎症反应。高迁移率族蛋白1(HMGB1)是一种重要的炎症介质，参与了脓毒症的病理生理过程。在一项前瞻性观察性病例对照研究中，采用商品化的酶联免疫吸附试验对感染恶性疟原虫的乌干达发热儿童的血浆HMGB1水平进行了量化。HMGB1用于区分重症疟疾(SM；n = 70)和无并发症疟疾(UM；n = 33)以及致死性疟疾(n = 21)和非致死性疟疾(n = 82)。受试者操作特征曲线分析评估HMGB1的预后准确性。体外检测恶性疟原虫寄生红细胞从外周血单核细胞诱导HMGB1的能力。在实验性伯氏疟原虫和SM啮齿动物寄生虫模型中，评估了抗HMGB1中和抗体对疾病结局的影响。每天评估死亡率和寄生虫血症，并与接受同种抗体治疗的对照组进行比较。在恶性疟原虫感染的儿科患者中，入院时血浆HMGB1水平升高与SM和随后的致命结局显著相关。在体外，寄生的红细胞诱导人外周血单核细胞释放HMGB1。在严重疟疾的实验小鼠模型中，抗体介导的HMGB1中和未能降低死亡率。这些数据表明，HMGB1升高是人类SM疾病严重程度的信息预后标志物，但不支持HMGB1作为实验性小鼠SM治疗干预的可行靶点。
Severe falciparum malaria (SM) pathogenesis has been attributed, in part, to deleterious systemic host inflammatory responses to infection. High mobility group box 1 (HMGB1) protein is an important mediator of inflammation implicated in sepsis pathophysiology. Plasma levels of HMGB1 were quantified in a cohort of febrile Ugandan children with Plasmodium falciparum infection, enrolled in a prospective observational case-controlled study, using a commercial enzyme-linked immunosorbent assay. The utility of HMGB1 to distinguish severe malaria (SM; n = 70) from uncomplicated malaria (UM; n = 33) patients and fatal (n = 21) versus non-fatal (n = 82) malaria, at presentation, was examined. Receiver operating characteristic curve analysis was used to assess the prognostic accuracy of HMGB1. The ability of P. falciparum-parasitized erythrocytes to induce HMGB1 from peripheral blood mononuclear cells was assessed in vitro. The effect of an anti-HMGB1 neutralizing antibody on disease outcome was assessed in the experimental Plasmodium berghei ANKA rodent parasite model of SM. Mortality and parasitaemia was assessed daily and compared to isotype antibody-treated controls. Elevated plasma HMGB1 levels at presentation were significantly associated with SM and a subsequent fatal outcome in paediatric patients with P. falciparum infection. In vitro, parasitized erythrocytes induced HMGB1 release from human peripheral blood mononuclear cells. Antibody-mediated neutralization of HMGB1 in the experimental murine model of severe malaria failed to reduce mortality. These data suggest that elevated HMGB1 is an informative prognostic marker of disease severity in human SM, but do not support HMGB1 as a viable target for therapeutic intervention in experimental murine SM.
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影响因子：
168.9
作者：
Dondorp, Arjen M.;Fanello, Caterina I.;White, Nicholas J.
通讯作者：
White, Nicholas J.
影响因子：
56.9
作者：
GRAU, GE;FAJARDO, LF;VASSALLI, P
通讯作者：
VASSALLI, P
影响因子：
6
作者：
Togbe, Dieudonnee;Schofield, Louis;Ryffel, Bernhard
通讯作者：
Ryffel, Bernhard
DOI：
10.4049/jimmunol.1200688
发表时间：
2012-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Villegas-Mendez A;Greig R;Shaw TN;de Souza JB;Gwyer Findlay E;Stumhofer JS;Hafalla JC;Blount DG;Hunter CA;Riley EM;Couper KN
通讯作者：
Couper KN
DOI：
10.1016/j.trstmh.2004.06.008
发表时间：
2005-03-01
影响因子：
2.2
作者：
Alleva, LM;Yang, H;Clark, IA
通讯作者：
Clark, IA