Association of low serum TGF-β level in hantavirus infected patients with severe disease.

Mahmoud Sadeghi,Volker Daniel,Martin Zeier,Mojdeh Heidary Navid,Imad Lahdou,Jörg Hofmann,Gerhard Opelz,Paul Schnitzler,Jakob Ettinger

doi:10.1186/s12865-015-0085-0

Mahmoud Sadeghi, Volker Daniel + Show 7 more

Open Access

https://doi.org/10.1186/s12865-015-0085-0

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Abstract

BackgroundHantaviruses 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.ResultsWe 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.ConclusionHigh 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.

Highlights

Hantaviruses are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome, an immune-mediated pathogenesis is discussed
Three main clinical syndromes can be distinguished after hantavirus infection, i.e. hemorrhagic fever with renal syndrome (HFRS) mainly caused by Seoul, Puumala and Dobrava viruses; nephropathia epidemica, a mild form of HFRS caused by Puumala virus; and hantavirus cardiopulmonary syndrome, which may be caused by Andes virus and Sin Nombre virus
Patients with a severe course of disease defined by a glomerular filtration rate (GFR) of

Summary

Introduction

Hantaviruses are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome, an immune-mediated pathogenesis is discussed. Three main clinical syndromes can be distinguished after hantavirus infection, i.e. hemorrhagic fever with renal syndrome (HFRS) mainly caused by Seoul, Puumala and Dobrava viruses; nephropathia epidemica, a mild form of HFRS caused by Puumala virus; and hantavirus cardiopulmonary syndrome, which may be caused by Andes virus and Sin Nombre virus. Over 50 000 nephropathia epidemica cases with Puumala virus infections have been registered in Europe, and even over. Infection in humans occurs through inhalation of aerosolised virus particles from excreta of chronically infected wild rodents [4]. In Germany, several hantaviruses pathogenic for humans are circulating, i.e. Puumala virus, Dobrava virus and Tula virus [6,7]. Puumala virus is carried by the bank vole (Clethrionomys glareolus) and leads mostly to a mild form of disease [3]

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