title: Complement activation in nephropathia epidemica caused by Puumala hantavirus.
abstract: OBJECTIVE
  Nephropathia epidemica (NE) is a hemorrhagic fever with renal syndrome caused by Puumala hantavirus. There is considerable variability in the clinical severity of NE. Its pathogenesis is largely unknown and data on complement activation in NE are scant. We sought here to establish how the complement system behaves during NE and whether the variation in the clinical outcome is related to the activation of complement.
  
  
  METHODS
  The complement component levels and complement activation products and the clinical course of 25 hospital-treated acutely ill NE patients were studied.
  
  
  RESULTS
  Complement activation was observed in 23 patients. In 10 patients the complement system was activated mainly through the alternative route, in 6 mainly through the classical route and in 5 through both the alternative and the classical route. An elevated soluble terminal complex SC5b-9 was the most sensitive indicator of complement activation (17 out of 25 patients). Two patients had only an elevated SC5b-9 value and 2 had no complement activation. The C4d/C4 maximal ratio was significantly higher in patients with clinically severe NE compared to the mild or moderate disease groups.
  
  
  CONCLUSIONS
  Our results show that complement activation is common in NE. Although both pathways are usually activated, the classical pathway activation by immune complexes or directly by viral components is associated with a severe clinical course of NE.
authors.affiliation: Medical School, University of Tampere, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Paakkala
authors.forename: J
authors.initials: J
authors.lastname: Mustonen
authors.forename: M
authors.initials: M
authors.lastname: Viander
authors.forename: H
authors.initials: H
authors.lastname: Huhtala
authors.forename: A
authors.initials: A
authors.lastname: Pasternack
mesh_terms: D000293:Adolescent; D000328:Adult; D003167:Complement Activation; D015933:Complement C3d / Q000276:immunology; D003181:Complement C4 / Q000276:immunology; D015935:Complement C4b; D015938:Complement Membrane Attack Complex; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D006476:Orthohantavirus; D018778:Hantavirus Infections / Q000276:immunology* / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology
chemical_list: D003181:Complement C4; D015938:Complement Membrane Attack Complex; D006023:Glycoproteins; D010446:Peptide Fragments; C047610:SC5b-9 protein complex; D015933:Complement C3d; D015935:Complement C4b; C032261:complement C4d; D003165:Complement System Proteins