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High pentraxin-3 plasma levels associate with thrombocytopenia in acute Puumala hantavirus-induced nephropathia epidemica

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Abstract

Our aim was to investigate whether plasma levels of the long pentraxin-3 (PTX3) associate with the severity of Puumala hantavirus-induced nephropathia epidemica (NE). Sixty-one prospectively identified consecutively hospitalized NE patients were examined. Plasma PTX3, interleukin (IL)-6, terminal complement complex SC5b-9, complement component C3, C-reactive protein (CRP), creatinine, sodium, kynurenine, and tryptophan levels, as well as the blood cell count, were determined for up to five consecutive days after hospitalization. Receiver operating characteristic (ROC) analysis revealed that the maximum PTX3 level >101.6 ng/ml (high PTX3) showed a sensitivity of 71% and a specificity of 89% for detecting platelet level <50 × 109/l, with an area under the curve (AUC) value of 0.78 (95% confidence interval [CI] 0.63–0.94). High PTX3 level was also associated with several other variables reflecting the severity of the disease: patients with high PTX3 level had higher maximum blood leukocyte (16.1 vs. 9.7 × 109/l, p < 0.001), plasma IL-6 (16.9 vs. 9.0 pg/ml, p = 0.007), and creatinine (282 vs. 124 μmol/l, p = 0.007) levels than patients with low maximum PTX3 level. They also had longer hospital stays (8 vs. 5 days, p = 0.015) compared to patients with low PTX3 level. High plasma PTX3 levels are associated with thrombocytopenia and the overall severity of NE.

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References

  1. Vapalahti O, Mustonen J, Lundkvist Å, Henttonen H, Plyusnin A, Vaheri A (2003) Hantavirus infections in Europe. Lancet Infect Dis 3:653–661

    Article  PubMed  Google Scholar 

  2. Brummer-Korvenkontio M, Vaheri A, Hovi T, von Bonsdorff CH, Vuorimies J, Manni T, Penttinen K, Oker-Blom N, Lähdevirta J (1980) Nephropathia epidemica: detection of antigen in bank voles and serologic diagnosis of human infection. J Infect Dis 141:131–134

    Article  PubMed  CAS  Google Scholar 

  3. Kanerva M, Mustonen J, Vaheri A (1998) Pathogenesis of Puumala and other hantavirus infections. Rev Med Virol 8:67–86

    Article  PubMed  Google Scholar 

  4. Lähdevirta J (1971) Nephropathia epidemica in Finland. A clinical histological and epidemiological study. Ann Clin Res 3:1–54

    PubMed  Google Scholar 

  5. Mustonen J, Brummer-Korvenkontio M, Hedman K, Pasternack A, Pietilä K, Vaheri A (1994) Nephropathia epidemica in Finland: a retrospective study of 126 cases. Scand J Infect Dis 26:7–13

    Article  PubMed  CAS  Google Scholar 

  6. Makary P, Kanerva M, Ollgren J, Virtanen MJ, Vapalahti O, Lyytikäinen O (2010) Disease burden of Puumala virus infections, 1995–2008. Epidemiol Infect 138:1484–1492

    Article  PubMed  CAS  Google Scholar 

  7. Settergren B, Juto P, Trollfors B, Wadell G, Norrby SR (1989) Clinical characteristics of nephropathia epidemica in Sweden: prospective study of 74 cases. Rev Infect Dis 11:921–927

    Article  PubMed  CAS  Google Scholar 

  8. Outinen TK, Mäkelä SM, Ala-Houhala IO, Huhtala HS, Hurme M, Paakkala AS, Pörsti IH, Syrjänen JT, Mustonen JT (2010) The severity of Puumala hantavirus induced nephropathia epidemica can be better evaluated using plasma interleukin-6 than C-reactive protein determinations. BMC Infect Dis 10:132

    Article  PubMed  Google Scholar 

  9. Outinen TK, Mäkelä SM, Ala-Houhala IO, Huhtala HSA, Hurme M, Libraty DH, Oja SS, Pörsti IH, Syrjänen JT, Vaheri A, Mustonen JT (2011) High activity of indoleamine 2,3-dioxygenase is associated with renal insufficiency in Puumala hantavirus induced nephropathia epidemica. J Med Virol 83:731–737

    Article  PubMed  CAS  Google Scholar 

  10. Paakkala A, Mustonen J, Viander M, Huhtala H, Pasternack A (2000) Complement activation in nephropathia epidemica caused by Puumala hantavirus. Clin Nephrol 53:424–431

    PubMed  CAS  Google Scholar 

  11. Sane J, Laine O, Mäkelä S, Paakkala A, Jarva H, Mustonen J, Vapalahti O, Meri S, Vaheri A (2011) Complement activation in Puumala hantavirus infection correlates with disease severity. Ann Med (in press)

  12. Bottazzi B, Garlanda C, Cotena A, Moalli F, Jaillon S, Deban L, Mantovani A (2009) The long pentraxin PTX3 as a prototypic humoral pattern recognition receptor: interplay with cellular innate immunity. Immunol Rev 227:9–18

    Article  PubMed  CAS  Google Scholar 

  13. Mantovani A, Garlanda C, Doni A, Bottazzi B (2008) Pentraxins in innate immunity: from C-reactive protein to the long pentraxin PTX3. J Clin Immunol 28:1–13

    Article  PubMed  CAS  Google Scholar 

  14. Mantovani A, Garlanda C, Bottazzi B, Peri G, Doni A, Martinez de la Torre Y, Latini R (2006) The long pentraxin PTX3 in vascular pathology. Vascul Pharmacol 45:326–330

    Article  PubMed  CAS  Google Scholar 

  15. Jaillon S, Peri G, Delneste Y, Frémaux I, Doni A, Moalli F, Garlanda C, Romani L, Gascan H, Bellocchio S, Bozza S, Cassatella MA, Jeannin P, Mantovani A (2007) The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localizes in extracellular traps. J Exp Med 204:793–804

    Article  PubMed  CAS  Google Scholar 

  16. Deban L, Bottazzi B, Garlanda C, de la Torre YM, Mantovani A (2009) Pentraxins: multifunctional proteins at the interface of innate immunity and inflammation. Biofactors 35:138–145

    Article  PubMed  CAS  Google Scholar 

  17. Bottazzi B, Vouret-Craviari V, Bastone A, De Gioia L, Matteucci C, Peri G, Spreafico F, Pausa M, D’Ettorre C, Gianazza E, Tagliabue A, Salmona M, Tedesco F, Introna M, Mantovani A (1997) Multimer formation and ligand recognition by the long pentraxin PTX3. Similarities and differences with the short pentraxins C-reactive protein and serum amyloid P component. J Biol Chem 272:32817–32823

    Article  PubMed  CAS  Google Scholar 

  18. Deban L, Jarva H, Lehtinen MJ, Bottazzi B, Bastone A, Doni A, Jokiranta TS, Mantovani A, Meri S (2008) Binding of the long pentraxin PTX3 to factor H: interacting domains and function in the regulation of complement activation. J Immunol 181:8433–8440

    PubMed  CAS  Google Scholar 

  19. Vapalahti O, Lundkvist Å, Kallio-Kokko H, Paukku K, Julkunen I, Lankinen H, Vaheri A (1996) Antigenic properties and diagnostic potential of Puumala virus nucleocapsid protein expressed in insect cells. J Clin Microbiol 34:119–125

    PubMed  CAS  Google Scholar 

  20. Laine O, Mäkelä S, Mustonen J, Huhtala H, Szanto T, Vaheri A, Lassila R, Joutsi-Korhonen L (2010) Enhanced thrombin formation and fibrinolysis during acute Puumala hantavirus infection. Thromb Res 126:154–158

    Article  PubMed  CAS  Google Scholar 

  21. Mäkelä S, Mustonen J, Ala-Houhala I, Hurme M, Koivisto AM, Vaheri A, Pasternack A (2004) Urinary excretion of interleukin-6 correlates with proteinuria in acute Puumala hantavirus-induced nephritis. Am J Kidney Dis 43:809–816

    Article  PubMed  Google Scholar 

  22. Schröcksnadel K, Wirleitner B, Winkler C, Fuchs D (2006) Monitoring tryptophan metabolism in chronic immune activation. Clin Chim Acta 364:82–90

    Article  PubMed  Google Scholar 

  23. Laich A, Neurauter G, Widner B, Fuchs D (2002) More rapid method for simultaneous measurement of tryptophan and kynurenine by HPLC. Clin Chem 48:579–581

    PubMed  CAS  Google Scholar 

  24. Boyd JC (1997) Mathematical tools for demonstrating the clinical usefulness of biochemical markers. Scand J Clin Lab Invest Suppl 227:46–63

    PubMed  CAS  Google Scholar 

  25. Huttunen R, Hurme M, Aittoniemi J, Huhtala H, Vuento R, Laine J, Jylhävä J, Syrjänen J (2011) High plasma level of long pentraxin 3 (PTX3) is associated with fatal disease in bacteremic patients: a prospective cohort study. PLos One 6(7):e21700

    Article  PubMed  CAS  Google Scholar 

  26. Mairuhu AT, Peri G, Setiati TE, Hack CE, Koraka P, Soemantri A, Osterhaus AD, Brandjes DP, van der Meer JW, Mantovani A, van Gorp EC (2005) Elevated plasma levels of the long pentraxin, pentraxin 3, in severe dengue virus infections. J Med Virol 76:547–552

    Article  PubMed  CAS  Google Scholar 

  27. Garlanda C, Bottazzi B, Bastone A, Mantovani A (2005) Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility. Annu Rev Immunol 23:337–366

    Article  PubMed  CAS  Google Scholar 

  28. Reading PC, Bozza S, Gilbertson B, Tate M, Moretti S, Job ER, Crouch EC, Brooks AG, Brown LE, Bottazzi B, Romani L, Mantovani A (2008) Antiviral activity of the long chain pentraxin PTX3 against influenza viruses. J Immunol 180:3391–3398

    PubMed  CAS  Google Scholar 

  29. Bozza S, Bistoni F, Gaziano R, Pitzurra L, Zelante T, Bonifazi P, Perruccio K, Bellocchio S, Neri M, Iorio AM, Salvatori G, De Santis R, Calvitti M, Doni A, Garlanda C, Mantovani A, Romani L (2006) Pentraxin 3 protects from MCMV infection and reactivation through TLR sensing pathways leading to IRF3 activation. Blood 108:3387–3396

    Article  PubMed  CAS  Google Scholar 

  30. Wagenaar JF, Goris MG, Gasem MH, Isbandrio B, Moalli F, Mantovani A, Boer KR, Hartskeerl RA, Garlanda C, van Gorp EC (2009) Long pentraxin PTX3 is associated with mortality and disease severity in severe Leptospirosis. J Infect 58:425–432

    Article  PubMed  Google Scholar 

  31. Azzurri A, Sow OY, Amedei A, Bah B, Diallo S, Peri G, Benagiano M, D’Elios MM, Mantovani A, Del Prete G (2005) IFN-gamma-inducible protein 10 and pentraxin 3 plasma levels are tools for monitoring inflammation and disease activity in Mycobacterium tuberculosis infection. Microbes Infect 7:1–8

    Article  PubMed  CAS  Google Scholar 

  32. Sprong T, Peri G, Neeleman C, Mantovani A, Signorini S, van der Meer JW, van Deuren M (2009) Pentraxin 3 and C-reactive protein in severe meningococcal disease. Shock 31:28–32

    Article  PubMed  CAS  Google Scholar 

  33. Mauri T, Bellani G, Patroniti N, Coppadoro A, Peri G, Cuccovillo I, Cugno M, Iapichino G, Gattinoni L, Pesenti A, Mantovani A (2010) Persisting high levels of plasma pentraxin 3 over the first days after severe sepsis and septic shock onset are associated with mortality. Intensive Care Med 36:621–629

    Article  PubMed  CAS  Google Scholar 

  34. Muller B, Peri G, Doni A, Torri V, Landmann R, Bottazzi B, Mantovani A (2001) Circulating levels of the long pentraxin PTX3 correlate with severity of infection in critically ill patients. Crit Care Med 29:1404–1407

    Article  PubMed  CAS  Google Scholar 

  35. de Kruif MD, Limper M, Sierhuis K, Wagenaar JF, Spek CA, Garlanda C, Cotena A, Mantovani A, ten Cate H, Reitsma PH, van Gorp EC (2010) PTX3 predicts severe disease in febrile patients at the emergency department. J Infect 60:122–127

    Article  PubMed  Google Scholar 

  36. Garlanda C, Hirsch E, Bozza S, Salustri A, De Acetis M, Nota R, Maccagno A, Riva F, Bottazzi B, Peri G, Doni A, Vago L, Botto M, De Santis R, Carminati P, Siracusa G, Altruda F, Vecchi A, Romani L, Mantovani A (2002) Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature 420:182–186

    Article  PubMed  CAS  Google Scholar 

  37. Gaziano R, Bozza S, Bellocchio S, Perruccio K, Montagnoli C, Pitzurra L, Salvatori G, De Santis R, Carminati P, Mantovani A, Romani L (2004) Anti-Aspergillus fumigatus efficacy of pentraxin 3 alone and in combination with antifungals. Antimicrob Agents Chemother 48:4414–4421

    Article  PubMed  CAS  Google Scholar 

  38. Peerschke EI, Yin W, Ghebrehiwet B (2008) Platelet mediated complement activation. Adv Exp Med Biol 632:81–91

    PubMed  CAS  Google Scholar 

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Acknowledgments

The study was financially supported by the Competitive Research Funding of the Tampere University Hospital, the European Commission Project “Diagnosis and control of rodent-borne viral zoonoses in Europe” (QLK2-CT-2002-01358), and the Finnish Kidney Foundation. The skillful technical assistance of Ms. Katriina Ylinikkilä and Ms. Mirja Ikonen is greatly appreciated.

Disclosure of interest

The authors report no conflicts of interest.

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Authors and Affiliations

  1. Department of Internal Medicine, Tampere University Hospital, P.O. Box 2000, 33521, Tampere, Finland

    T. K. Outinen, S. Mäkelä, I. Pörsti, J. Syrjänen & J. Mustonen

  2. School of Medicine, University of Tampere, 33014, Tampere, Finland

    S. Mäkelä, M. Hurme, I. Pörsti, J. Syrjänen & J. Mustonen

  3. School of Health Sciences, University of Tampere, 33014, Tampere, Finland

    H. Huhtala

  4. Laboratory Centre, Tampere University Hospital, P.O. Box 2000, 33521, Tampere, Finland

    M. Hurme

  5. Department of Bacteriology and Immunology, Infection Biology Research Program, Haartman Institute, University of Helsinki, P.O. Box 21, 00014, Helsinki, Finland

    S. Meri

  6. Division of Clinical Microbiology, Helsinki University Central Hospital Laboratory, HUSLAB, 00029, Helsinki, Finland

    S. Meri

  7. Department of Virology, Infection Biology Research Program, Haartman Institute, University of Helsinki, 00014, Helsinki, Finland

    J. Sane & A. Vaheri

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  1. T. K. Outinen
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  2. S. Mäkelä
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  7. J. Sane
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Correspondence to T. K. Outinen.

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Jaana Syrjänen and Jukka Mustonen contributed equally to this paper.

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Outinen, T.K., Mäkelä, S., Huhtala, H. et al. High pentraxin-3 plasma levels associate with thrombocytopenia in acute Puumala hantavirus-induced nephropathia epidemica. Eur J Clin Microbiol Infect Dis 31, 957–963 (2012). https://doi.org/10.1007/s10096-011-1392-x

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