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

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.

The prognostic significance of serum TGF‐β1 levels in patients with Crimean‐Congo hemorrhagic fever

“…TGF‐β1 is a multifunctional cytokine involved in the several pathological process, including inflammatory events and also tissue fibrosis by regulating procoagulant and fibrinolytic activities [Marshall et al, ; Jablonska et al, ; Oshima et al, ]. TGF‐β is reported in many viral infections, such as dengue hemorrhagic fever, hepatitis C virus infection, influenza, HIV, hepatitis B virus and hantavirus infection [Li et al, ; Pandey et al, ; Sadeghi et al, ]. As in our study, TGF‐β levels reported low in severely ill patients compared to mild patients [Deng et al, ; Pandey et al, ; Sadeghi et al, ].…”

“…TGF‐β is reported in many viral infections, such as dengue hemorrhagic fever, hepatitis C virus infection, influenza, HIV, hepatitis B virus and hantavirus infection [Li et al, ; Pandey et al, ; Sadeghi et al, ]. As in our study, TGF‐β levels reported low in severely ill patients compared to mild patients [Deng et al, ; Pandey et al, ; Sadeghi et al, ]. The coagulant‐anticoagulant balance is impaired by the stimulation of endothelial cells by inflammatory factors induced by CCHF.…”

Immune response during hantavirus diseases: implications for immunotherapies and vaccine design

“…96 On the contrary, suppressive cytokines, such as TGF-b1 and TGF-b2, are decreased in severe PUUV cases as compared to mild clinical courses. 105 Despite no differences in Treg frequency in PUUV cases in comparison with healthy donors, two main immune checkpoints involved in T-cell regulation, PD1 + and CTLA4 + , are elevated in CD4 + T cells. 95 Also, an increased frequency of Tregs is observed early in PUUV cases as compared to healthy controls and DOBV-infected individuals, 100 suggesting that regulatory mechanisms might be promoting a more balanced and less harmful immune response.…”

“…In the course of HFRS, it has been observed that FOXP3 expression levels are upregulated during PUUV infection and are directly correlated with hospitalization days, suggesting that Tregs play a role in disease severity 96 . On the contrary, suppressive cytokines, such as TGF‐β1 and TGF‐β2, are decreased in severe PUUV cases as compared to mild clinical courses 105 . Despite no differences in Treg frequency in PUUV cases in comparison with healthy donors, two main immune checkpoints involved in T‐cell regulation, PD1 + and CTLA4 + , are elevated in CD4 + T cells 95 .…”

Severity Biomarkers in Puumala Hantavirus Infection

“…High CRP could help in preserving kidney function by reducing the deposition and increasing the clearance of immune complexes in the renal cortex [33]. However, a German study found an association of high CRP with a more severe AKI [43]. Thus, the predictive and possible protective role of CRP in PUUV infection remains to be elucidated.…”