High Mobility Group Box 1 Protein as an Auxiliary Biomarker for Dengue Diagnosis

Diego Allonso Laboratory of Structural Genomics, Biophysics Institute Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil; Department of Virology, Pan American Health Organization/World Health Organization Collaborating Center for the Study of Dengue and its Vector, Pedro Kouri Tropical Medicine Institute, Havana, Cuba

Search for other papers by Diego Allonso in
Current site
Google Scholar
PubMed
Close
,
Susana Vázquez Laboratory of Structural Genomics, Biophysics Institute Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil; Department of Virology, Pan American Health Organization/World Health Organization Collaborating Center for the Study of Dengue and its Vector, Pedro Kouri Tropical Medicine Institute, Havana, Cuba

Search for other papers by Susana Vázquez in
Current site
Google Scholar
PubMed
Close
,
Maria G. Guzmán Laboratory of Structural Genomics, Biophysics Institute Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil; Department of Virology, Pan American Health Organization/World Health Organization Collaborating Center for the Study of Dengue and its Vector, Pedro Kouri Tropical Medicine Institute, Havana, Cuba

Search for other papers by Maria G. Guzmán in
Current site
Google Scholar
PubMed
Close
, and
Ronaldo Mohana-Borges Laboratory of Structural Genomics, Biophysics Institute Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil; Department of Virology, Pan American Health Organization/World Health Organization Collaborating Center for the Study of Dengue and its Vector, Pedro Kouri Tropical Medicine Institute, Havana, Cuba

Search for other papers by Ronaldo Mohana-Borges in
Current site
Google Scholar
PubMed
Close
Restricted access

Despite the availability of many methods for rapid and early diagnosis of dengue, there is still a need to develop new approaches that not only combine low cost, specificity, and sensitivity, but also are capable of accurately detecting secondary infection in the early stages of the disease. We report the potential of the high mobility group box 1 protein as an auxiliary biomarker for early dengue diagnosis. We tested a 205-sample serum panel that included negative and positive samples from primary and secondary dengue cases, as well as samples from patients with dengue-like symptoms. We observed that high mobility group box 1 protein was generally detected only in dengue-positive samples for persons with primary and secondary infections. These results highlight the possibility of using this endogenous molecule as an auxiliary biomarker to aid in dengue detection and improve current methods for early diagnosis of dengue.

Author Notes

* Address correspondence to Ronaldo Mohana-Borges, Laboratório de Genômica Estrutural, Instituto de Biofísica Carlos Chagas Filho, Edificio do Centro de Ciências da Saúde, Bloco C sala 36 Sub-solo, Av. Carlos Chagas Filho, s/n-Cidade Universitaria, Ilha do Fundao, CEP 21941-902, Rio de Janeiro, RJ, Brazil. E-mail: mohana@biof.ufrj.br

Financial support: This work was supported by CAPES, CNPq, FAPERJ, IMBEBB, and the National Institutes of Science and Technology in Structural Biology and Bioimaging (INCT-INBEB).

Authors' addresses: Diego Allonso and Ronaldo Mohana-Borges, Laboratory of Structural Genomics, Biophysics Institute Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil, E-mails: diegoars@biof.ufrj.br and mohana@biof.ufrj.br. Susana Vázquez and Maria G. Guzmán, Department of Virology, Pan American Health Organization/World Health Organization Collaborating Center for the Study of Dengue and its Vector, Pedro Kouri Tropical Medicine Institute, Havana, Cuba, E-mails: svazquez@ipk.sld.cu and lupe@ipk.sld.cu.

  • 1.

    Guzman MG, Halstead SB, Artsob H, Buchy P, Farrar J, Gubler DJ, Hunsperger E, Kroeger A, Margolis HS, Martínez E, Nathan MB, Pelegrino JL, Simmons C, Yoksan S, Peeling RW, 2010. Dengue: a continuing global threat. Nat Rev Microbiol 8: S7S16.

    • Search Google Scholar
    • Export Citation
  • 2.

    Simmons CP, Farrar JJ, Nguyen V, Wills B, 2012. Dengue. N Engl J Med 366: 14231432.

  • 3.

    Peeling RW, Artsob H, Pelegrino JL, Buchy P, Cardosa MJ, Devi S, Enria DA, Farrar J, Gubler DJ, Guzman MG, Halstead SB, Hunsperger E, Kliks S, Margolis HS, Nathanson CM, Nguyen VC, Rizzo N, Vázquez S, Yoksan S, 2010. Evaluation of diagnostic tests: dengue. Nat Rev Microbiol 8: S30S38.

    • Search Google Scholar
    • Export Citation
  • 4.

    Bianchi ME, Manfredi AA, 2007. High-mobility group box 1 (HMGB1) protein at the crossroads between innate and adaptive immunity. Immunol Rev 20: 3536.

    • Search Google Scholar
    • Export Citation
  • 5.

    Muller S, Scaffidi P, Degryse B, Bonaldi T, Ronfani L, Agresti A, Beltrame M, Bianchi ME, 2001. The double life of HMGB1 chromatin protein: architectural factor and extracellular signal. EMBO J 20: 43374340.

    • Search Google Scholar
    • Export Citation
  • 6.

    Scaffidi P, Misteli T, Bianchi ME, 2002. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418: 191195.

  • 7.

    Dumitriu IE, Baruah P, Valentinis B, Voll RE, Herrmann M, Nawroth PP, Arnold B, Bianchi ME, Manfredi AA, Rovere-Querini P, 2005. Release of high mobility group box 1 by dendritic cells controls T cell activation via the receptor for advanced glycation end products. J Immunol 174: 75067515.

    • Search Google Scholar
    • Export Citation
  • 8.

    Huang W, Tang Y, Li L, 2010. HMGB1, a potent proinflammatory cytokine in sepsis. Cytokine 51: 119126.

  • 9.

    Chen LC, Yeh TM, Wu HM, Lin YY, Shyu HW, 2008. Dengue virus infection induces passive release of high mobility group box 1 protein by epithelial cells. J Infect 56: 143150.

    • Search Google Scholar
    • Export Citation
  • 10.

    Kamau E, Takhampunya R, Li T, Kelly E, Peachman KK, Lynch JA, Sun P, Palmer DR, 2009. Dengue virus infection promotes translocation of high mobility group box 1 protein from the nucleus to the cytosol in dendritic cells, upregulates cytokine production and modulates virus replication. J Gen Virol 90: 18271835.

    • Search Google Scholar
    • Export Citation
  • 11.

    Allonso D, Belgrano FS, Calzada N, Guzman MG, Vazquez S, Mohana-Borges R, 2012. Elevated serum levels of high mobility group box 1 (HMGB1) protein in dengue-infected patients are associated with disease symptoms and secondary infection. J Clin Virol 55: 214219.

    • Search Google Scholar
    • Export Citation
  • 12.

    Wang H, Bloom O, Zhang M, Vishnubhakat JM, Ombrellino M, Che J, Frazier A, Yang H, Ivanova S, Borovikova L, Manogue KR, Faist E, Abraham E, Andersson J, Andersson U, Molina PE, Abumrad NN, Sama A, Tracey KJ, 1999. HMG-1 as a late mediator of endotoxin lethality in mice. Science 285: 248251.

    • Search Google Scholar
    • Export Citation
  • 13.

    Andersson U, Tracey KJ, 2011. HMGB1 is a therapeutic target for sterile inflammation and infection. Annu Rev Immunol 29: 139162.

  • 14.

    Nowak P, Barqasho B, Sonnerberg A, 2007. Elevated plasma levels of high mobility group box protein 1 in patients with HIV-1 infection. AIDS 21: 869871.

    • Search Google Scholar
    • Export Citation
  • 15.

    Torii Y, Ohta R, Imai M, Hara S, Kawano Y, Matsubayashi T, Inui A, Yoshikawa T, Nishimura N, Ozaki T, Morishima T, Kimura H, 2011. Increased levels of cytokines and high-mobility group box 1 are associated with the development of severe pneumonia, but not acute encephalopathy, in 2009 H1N1 influenza-infected children. Cytokine 56: 180187.

    • Search Google Scholar
    • Export Citation
Past two years Past Year Past 30 Days
Abstract Views 17 17 4
Full Text Views 314 97 0
PDF Downloads 70 20 0
 
Membership Banner
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save