Sibylle Bierbaum

Association of TNF-α with severe respiratory syncytial virus infection and bronchial asthma

Tumor necrosis factor (TNF‐)α is a proinflammatory cytokine that is important in the innate host defence and thus in the defence of infectious agents. However, in excess it provokes the development of chronic inflammatory diseases. The aim of this study was to test association of TNF with severe RSV bronchiolitis as example of an infectious disease and asthma as representative for a chronic inflammatory condition. The following study populations were genotyped for 4 polymorphisms within TNF‐β (rs909253) and TNF‐α (rs1799964, rs1799724, rs1800629): 322 asthmatic children, 151 children with severe respiratory syncytial virus (RSV) bronchiolitis and 270 controls. Furthermore, serum TNF‐α levels were measured by a FlowCytomix Assay. Asthma showed association with two TNF‐α polymorphisms as well as with TNF haplotpyes (p = 0.0050). In contrast, RSV bronchiolitis was associated with TNF haplotypes (p < 0.00001) but not with any single polymorphism. In addition, TNF‐α serum levels correlated with rs1799724 (p = 0.034). A genetically mediated up‐regulation of TNF‐α expression might provoke a pronounced inflammation of the airways and thus a more severe course of RSV infection as well as the onset of asthma. It remains to be elucidated whether severe RSV bronchiolitis starts TNF‐α upregulation and is one first step in the direction to asthma later in life, or whether both dieases are independent from each other and supported by TNF‐α upregulation.

Genetic polymorphisms of chitotriosidase in Caucasian children with bronchial asthma.

In humans, two types of chitinases have been identified: chitotriosidase I (CHIT1) and acid mammalian chitinase (AMCase). They are enzymes that cleave chitin, a polysaccharide contained in many different human parasites. So far, only little is known about their function in human and especially in human diseases. Recently we have described association of polymorphisms of AMCase with bronchial asthma in a pediatric population. In this study we were interested in whether CHIT1 is also involved in the genetics of asthma.

Confirmation of association of IL-15 with pediatric asthma and comparison of different controls

Background:  Interleukin (IL)‐15 is an important mediator in chronic inflammatory diseases. Recently, we have described the association of IL‐15 haplotypes with bronchial asthma. Asthma genetics is highly complex – about every second candidate gene is not confirmed in consecutive studies. We were interested in whether association of asthma with IL‐15 holds in a second population. Furthermore, we sought to investigate the effect of different controls.

Singleplex real-time RT-PCR for detection of influenza A virus and simultaneous differentiation of A/H1N1v and evaluation of the RealStar influenza kit

Abstract Background A novel influenza A virus, subtype A/H1N1v emerged in April 2009 and caused the first influenza pandemic of the 21st century. Reliable detection and differentiation from seasonal influenza viruses is mandatory for appropriate case management as well as public health. Objectives To develop and technically validate a novel one-step real-time RT-PCR assay which can be used for influenza A virus screening and subtyping of A/H1N1v in a singleplex fashion. To assess the clinical performance of a novel commercial influenza RT-PCR kit based on the in-house version. Study design A real-time RT-PCR assay targeting the matrix gene of influenza A viruses was developed and validated using in vitro transcribed RNA derived from influenza A/H1N1v, A/H1N1 and A/H3N2 virus as well as plaque-quantified influenza A/H1N1v, A/H1N1 and A/H3N2 virus samples. After validation of the in-house version the commercial RealStar kit was used to assess the clinical performance and specificity on a panel of influenza viruses including A/H1N1v, A/H1N1, swine A/H1N1, A/H3N2, avian A/H5N1 as well as patient specimens. Results The lower limit of detection of the in-house version was 2149, 1376 and 2994 RNA copies/ml for A/H1N1v, A/H1N1 and A/H3N2, respectively. The RealStar kit displayed 100% sensitivity and specificity and could reliably discriminate influenza A viruses from A/H1N1v. No cross reaction with swine A/H1N1 and A/H1N2 was observed with the RealStar A/H1N1v specific probe. Conclusion Both assays demonstrated high sensitivity and specificity and might assist in the diagnosis of suspected influenza cases.

Joint influences of Acidic‐Mammalian‐Chitinase with Interleukin‐4 and Toll‐like receptor‐10 with Interleukin‐13 in the genetics of asthma

Heinzmann A, Brugger M, Bierbaum S, Mailaparambil B, Kopp MV, Strauch K. Joint influences of Acidic‐Mammalian‐Chitinase with Interleukin‐4 and Toll‐like Receptor‐10 with Interleukin‐13 in the genetics of asthma.
Pediatr Allergy Immunol 2010: 21: e679–e686.
© 2010 John Wiley & Sons A/S

Influenza virus A(H1N1)pdm09 hemagglutinin polymorphism and associated disease in southern Germany during the 2010/11 influenza season

A novel influenza A virus emerged in early 2009 to cause the first influenza pandemic of the 21st century. Understanding the evolution of influenza virus is crucial to determine pathogenesis, vaccine efficacy, and resistance to antiviral drugs. In this study, we investigated the molecular evolution of influenza virus A(H1N1)pdm09 in the 2010/11 influenza season in southern Germany by sequence analysis of the influenza virus hemagglutinin gene from 25 patients with mild, moderate, and severe disease. Phylogenetic analysis revealed co-circulation of different genetic groups. The D222G mutation, which had previously been observed in severe cases, was not detected. Immunocompromised patients were not affected more severely than non-immunocompromised patients (p>0.05), although longer shedding was observed in some of them. Interestingly, additional mutations and potential glycosylation sites were detected in samples from the lower respiratory tract in two patients, but not in the corresponding upper respiratory tract specimens. The H275Y mutation in the influenza virus neuraminidase gene, known to confer resistance to the neuraminidase inhibitor oseltamivir, was detected in one patient.

Retrospective analysis of clinical and virological parameters of influenza cases at four university hospitals in Germany, 2015

We conducted a retrospective observational study at four German university hospitals of patients with laboratory-confirmed influenza in 2014/2015. Overall, a fatality rate of 8% was observed. Significantly more A(H1N1)pdm09 patients were admitted to ICU compared to those with A(H3N2). However, fatal outcome was not significantly increased among A(H1N1)pdm09 cases. Nosocomial infections were seen in 17% of cases. Systematic collection of data from hospitals will complement national influenza surveillance.