title: Association of low serum TGF-β level in hantavirus infected patients with severe disease.
abstract: BACKGROUND
  Hantaviruses are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome, an immune-mediated pathogenesis is discussed. The aim of the present study was to investigate the role of TGF-β expression in acute hantavirus infection.
  
  
  RESULTS
  We retrospectively studied 77 patients hospitalised with acute Puumala infection during a hantavirus epidemic in Germany in 2012. Hantavirus infection was confirmed by positive anti-Puumala hantavirus IgG and IgM. Plasma levels of transforming growth factor (TGF)-β1 and TGF-β2 were analysed. Based on glomerular filtration rate on admission, patients were divided in mild and severe course of disease. Puumala virus RNA was detected by PCR amplification of the viral L segment gene. Out of 77 Puumala virus infected patients, 52 (68%) were male. A seasonal distribution was detected in our cohort with a peak in summer 2012, the highest incidence was observed in the age group of 30-39 years. Puumala virus RNA was detectable in 4/77 cases. Patients with severe disease had a significant longer hospital stay than patients with mild disease (6.2 vs 3.6 days). Thrombocyte count (186 vs 225 per nl), serum TGF-β1 (74 vs 118 ng/l) and TGF-β2 (479 vs 586 pg/l) were significantly lower in severe compared to mild disease. However, C-reactive protein (CRP) was significantly higher in patients with severe disease (62 vs 40 mg/l). TGF-β1/Cr was the most sensitive and specific marker associated with renal dysfunction.
  
  
  CONCLUSIONS
  High serum CRP and low serum TGF-β in the early phase of hantavirus infection is associated with a severe course of disease. Our results support the hypothesis of an immune-mediated pathogenesis in hantavirus infection.
authors.affiliation: Department of Transplantation Immunology, University of Heidelberg, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany. mahmoud.sadeghi@med.uni-heidelberg.de.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Sadeghi
authors.affiliation: Department of Transplantation Immunology, University of Heidelberg, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany. imad.lahdou@med.uni-heidelnerg.de.
authors.forename: Imad
authors.initials: I
authors.lastname: Lahdou
authors.affiliation: Institute of Medical Virology, Charité University Medicine Berlin, Charitéplatz 1, 10117, Berlin, Germany. jakob.ettinger@charite.de.
authors.forename: Jakob
authors.initials: J
authors.lastname: Ettinger
authors.affiliation: Department of Infectious Diseases, Virology, University of Heidelberg, Im Neuenheimer Feld 324, 69120, Heidelberg, Germany. mojdehnavid@yahoo.com.
authors.forename: Mojdeh Heidary
authors.initials: MH
authors.lastname: Navid
authors.affiliation: Department of Transplantation Immunology, University of Heidelberg, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany. volker.daniel@med.uni-heidelberg.de.
authors.forename: Volker
authors.initials: V
authors.lastname: Daniel
authors.affiliation: Department of Nephrology, University of Heidelberg, Im Neuenheimer Feld 162, 69120, Heidelberg, Germany. martin.zeier@med.uni-heidelberg.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Zeier
authors.affiliation: Institute of Medical Virology, Charité University Medicine Berlin, Charitéplatz 1, 10117, Berlin, Germany. joerg.hofmann@charite.de.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hofmann
authors.affiliation: Department of Transplantation Immunology, University of Heidelberg, Im Neuenheimer Feld 305, 69120, Heidelberg, Germany. gerhard.opelz@med.uni-heidelberg.de.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Opelz
authors.affiliation: Department of Infectious Diseases, Virology, University of Heidelberg, Im Neuenheimer Feld 324, 69120, Heidelberg, Germany. paul.schnitzler@med.uni-heidelberg.de.
authors.forename: Paul
authors.initials: P
authors.lastname: Schnitzler
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D015331:Cohort Studies; D018450:Disease Progression; D058872:Epidemics; D005260:Female; D005858:Germany / Q000453:epidemiology; D006476:Orthohantavirus / Q000502:physiology*; D006480:Hemorrhagic Fever with Renal Syndrome / Q000453:epidemiology / Q000276:immunology*; D006801:Humans; D007902:Length of Stay; D008297:Male; D012367:RNA, Viral / Q000032:analysis; D012189:Retrospective Studies; D012621:Seasons; D016212:Transforming Growth Factor beta / Q000097:blood*
chemical_list: D015415:Biomarkers; D012367:RNA, Viral; D016212:Transforming Growth Factor beta; D002097:C-Reactive Protein