Elevated Plasma Soluble ST2 Levels  are Associated With Neuronal Injury and Neurocognitive Impairment in Children With Cerebral Malaria

Fernander, Elizabeth; Adogamhe, P.E.; Datta, Dibyadyuti; Bond, Caitlin; Zhao, Yi; Bangirana, Paul; Conroy, Andrea L.; Opoka, Robert O.; John, Chandy C.

doi:10.20411/pai.v7i1.499

Cited by 9 publications

(6 citation statements)

References 54 publications

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“…Furthermore, we observed an inverse correlation between anti-PF4/P IgG and circulating platelet count in Ret+ CM (Rs=-0.201, p=0.048; Supplemental Table S1, Figure 4A). (55)(56)(57). Anti-PF4/P antibodies have not been described in association with anemia, but we observed an inverse correlation in UM cases between anti-PF4/P and Hemoglobin (HgB: Rs=-0.225, p=0.015) and packed cell volume (PCV: Rs=-0.200, p=0.029) (Supplemental Table S1).…”

Section: Anti-pf4/p Antibodies Are Associated With Markers Of Thrombo...mentioning

confidence: 62%

“…ST2 levels are also positively associated with anti-PF4/P IgG levels and negatively associated with peripheral platelet count. ST2 is an interleukin-1-like receptor to the alarmin interleukin 33 (IL-33), associated with neuroinflammation and vascular dysfunction (68-70), and was recently described as a prognostic marker of neurological sequelae in children with CM (55).…”

Section: Discussionmentioning

confidence: 99%

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Prothrombotic autoantibodies targeting platelet factor 4/polyanion are associated with pediatric cerebral malaria

Vera,

Kessler,

Harawa

et al. 2024

Journal of Clinical Investigation

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Background. Features of consumptive coagulopathy and thromboinflammation are prominent in cerebral malaria (CM). We hypothesized that thrombogenic autoantibodies contribute to a procoagulant state in CM.Methods. Plasma from children with uncomplicated malaria (UM, n=124) and CM (n=136) was analyzed by ELISA for a panel of 8 autoantibodies including anti-Platelet Factor 4/polyanion (anti-PF4/P), anti-Phospholipid, anti-Phosphatidylserine, anti-Myeloperoxidase, anti-Proteinase 3, anti-dsDNA, anti-Beta-2-Glycoprotein I (β2GPI), and anti-Cardiolipin. Non-malarial coma (NMC, n=49) and healthy controls (HC, n=56) were assayed for comparison. Associations with clinical and immune biomarkers were determined using univariate and logistic regression analyses.Results. Median anti-PF4/P and anti-PS IgG levels were elevated with malaria infection relative to HC (p<0.001) and NMC (PF4/P: p<0.001). Anti-PF4/P IgG levels were elevated in CM (median=0.27, IQR: 0.19-0.41) compared to UM (median=0.19, IQR: 0.14-0.22, p=<0.0001). Anti-PS IgG levels did not differ between UM and CM (p=0.39). When CM cases were stratified by malaria retinopathy (Ret) status, levels of anti-PF4/P IgG correlated negatively with peripheral platelet count in Ret+ CM cases (Rs= 0.201, p=0.04) and associated positively with mortality (OR=15.2, 95% CI: 1.02 -275, p=0.048).Plasma from CM patients induced greater platelet activation in an ex-vivo assay relative to plasma from UM patients (p=0.02), and the observed platelet activation was associated with anti-PF4/P IgG levels (Rs= 0.293, p=0.035). Conclusions.Thrombosis mediated by elevated anti-PF4/P autoantibodies may be one mechanism contributing to the clinical complications of CM.

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Section: Anti-pf4/p Antibodies Are Associated With Markers Of Thrombo...mentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Prothrombotic autoantibodies targeting platelet factor 4/polyanion are associated with pediatric cerebral malaria

Vera,

Kessler,

Harawa

et al. 2024

Journal of Clinical Investigation

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“…Elevated concentrations of plasma sST2 levels were significantly associated with cognitive impairment in acute ischemic stroke patients [ 142 , 143 ]. Elevated plasma levels of sST2 may contribute to neuronal injury and long-term neurocognitive impairment in older children with cerebral malaria [ 144 ]. Its ability to bind two different isoforms of ST2 may at least partly account for the dual roles of IL-33.…”

Section: Discussionmentioning

confidence: 99%

Dual roles of interleukin-33 in cognitive function by regulating central nervous system inflammation

et al. 2022

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With the advent of an aging society, the incidence of dementia is increasing, resulting in a vast burden on society. It is increasingly acknowledged that neuroinflammation is implicated in various neurological diseases with cognitive dysfunction such as Alzheimer’s disease, multiple sclerosis, ischemic stroke, traumatic brain injury, and central nervous system infections. As an important neuroinflammatory factor, interleukin-33 (IL-33) is highly expressed in various tissues and cells in the mammalian brain, where it plays a role in the pathogenesis of a number of central nervous system conditions. Reams of previous studies have shown that IL-33 has both pro- and anti-inflammatory effects, playing dual roles in the progression of diseases linked to cognitive impairment by regulating the activation and polarization of immune cells, apoptosis, and synaptic plasticity. This article will summarize the current findings on the effects IL-33 exerts on cognitive function by regulating neuroinflammation, and attempt to explore possible therapeutic strategies for cognitive disorders based on the adverse and protective mechanisms of IL-33.

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“…What's more, serum soluble ST2 (sST2) which is a receptor of interleukin-33 can play an important role in acting as a potential prognostic biomarker for TBI 11 . Nowadays, it has been found that sST2 are associated with neuronal injury and neurocognitive impairment in CM patient 12 .…”

Section: Correlations Between Cerebral Malaria and Traumatic Brain In...mentioning

confidence: 99%

Recrudescent plasmodium falciparum malaria after head trauma: a case report with novel clinical perspective

Liu,

Wang,

et al. 2023

Preprint

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Malaria is a common infection disease in tropical regions, among which cerebral malaria caused by Plasmodium Falciparum remains an enormous threat. Recrudescence of Plasmodium falciparum malaria makes it hard to eliminate the disease of malaria. Many factors that can lead to immune suppression are believed to have the function of causing malaria recrudescence, but whether traumatic brain injury can trigger it remains unclear. Here we present a Plasmodium Falciparum malaria patient who had explicit traumatic brain injury history just before the onset of his symptoms of cerebral malaria. Besides, the progression of his cerebral malaria is much more rapid than normal. Throughout the case report we discuss a new provoking factor that may promote the recrudescence of Plasmodium Falciparum malaria and propose a novel perspective to avoid or reduce acute kidney injury in patients with cerebral malaria.

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Elevated Plasma Soluble ST2 Levels are Associated With Neuronal Injury and Neurocognitive Impairment in Children With Cerebral Malaria

Cited by 9 publications

References 54 publications

Prothrombotic autoantibodies targeting platelet factor 4/polyanion are associated with pediatric cerebral malaria

Prothrombotic autoantibodies targeting platelet factor 4/polyanion are associated with pediatric cerebral malaria

Dual roles of interleukin-33 in cognitive function by regulating central nervous system inflammation

Recrudescent plasmodium falciparum malaria after head trauma: a case report with novel clinical perspective

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