Elevated Levels of High-Mobility Group Box-1 (HMGB1) in Patients with Severe or Uncomplicated Plasmodium falciparum Malaria

Davide Angeletti Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Department of Biochemistry, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda

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Mpungu Steven Kiwuwa Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Department of Biochemistry, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda

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Justus Byarugaba Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Department of Biochemistry, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda

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Fred Kironde Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Department of Biochemistry, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda

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Mats Wahlgren Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, School of Medicine, Makerere University College of Health Sciences, Kampala, Uganda; Department of Biochemistry, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda

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Severe malaria is characterized by a massive release of proinflammatory cytokines in the context of sequestration of parasitized and normal red cells (RBCs). High-mobility group box 1 (HMGB1) is a DNA- and heparin-binding protein that also acts as a cytokine when released from cells in the extracellular milieu after a proinflammatory stimulus. In this study, we have measured the circulating levels of HMGB1 in 76 children with severe or uncomplicated malaria. Sera from both severe (P = 0.0022) and uncomplicated (P = 0.0049) patients had significantly higher circulating HMGB1 levels compared with healthy controls. Elevated HMGB1 in patients with ongoing Plasmodium falciparum infections might prolong inflammation and the febrile state of malaria and could offer a potential target for therapeutic intervention.

Author Notes

* Address correspondence to Mats Wahlgren, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Box 280, Nobels vag 16, SE-171 77 Stockholm, Sweden. E-mail: mats.wahlgren@ki.se

Grants: This work was supported by Swedish Research Council (Vetenskapsrådet, VR) Grant VR/2012-2014/521-2011-3377, the Swedish Academy of Sciences (Kungliga Vetenskaps Akademin [KVA]; Söderberg Foundation), Karolinska Institutet—Distinguished Professor Award (DPA), and the European Union Network of Excellence EviMalar.

Authors' addresses: Davide Angeletti and Mats Wahlgren, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden, E-mails: Davide.angeletti@ki.se and Mats.wahlgren@ki.se. Mpungu Steven Kiwuwa and Justus Byarugaba, Makerere University College of Health Sciences, School of Medicine, Department of Pediatrics, Kampala, Uganda, E-mails: mkiwuwa@yahoo.com and byarugabaj@yahoo.com. Fred Kironde, Makerere University College of Health Sciences, School of Biomedical Sciences, Department of Biochemistry, Kampala, Uganda, E-mail: kironde@starcom.co.ug.

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