TY  - JOUR
A1  - Dix, Andreas
A1  - Czakai, Kristin
A1  - Springer, Jan
A1  - Fliesser, Mirjam
A1  - Bonin, Michael
A1  - Guthke, Reinhard
A1  - Schmitt, Anna L.
A1  - Einsele, Hermann
A1  - Linde, Jörg
A1  - Löffler, Jürgen
T1  - Genome-Wide Expression Profiling Reveals S100B as Biomarker for Invasive Aspergillosis
JF  - Frontiers in Microbiology
N2  - Invasive aspergillosis (IA) is a devastating opportunistic infection and its treatment constitutes a considerable burden for the health care system. Immunocompromised patients are at an increased risk for IA, which is mainly caused by the species Aspergillus fumigatus. An early and reliable diagnosis is required to initiate the appropriate antifungal therapy. However, diagnostic sensitivity and accuracy still needs to be improved, which can be achieved at least partly by the definition of new biomarkers. Besides the direct detection of the pathogen by the current diagnostic methods, the analysis of the host response is a promising strategy toward this aim. Following this approach, we sought to identify new biomarkers for IA. For this purpose, we analyzed gene expression profiles of hematological patients and compared profiles of patients suffering from IA with non-IA patients. Based on microarray data, we applied a comprehensive feature selection using a random forest classifier. We identified the transcript coding for the S100 calcium-binding protein B (S100B) as a potential new biomarker for the diagnosis of IA. Considering the expression of this gene, we were able to classify samples from patients with IA with 82.3% sensitivity and 74.6% specificity. Moreover, we validated the expression of S100B in a real-time reverse transcription polymerase chain reaction (RT-PCR) assay and we also found a down-regulation of S100B in A. fumigatus stimulated DCs. An influence on the IL1B and CXCL1 downstream levels was demonstrated by this S100B knockdown. In conclusion, this study covers an effective feature selection revealing a key regulator of the human immune response during IA. S100B may represent an additional diagnostic marker that in combination with the established techniques may improve the accuracy of IA diagnosis.
KW  - human biomarker
KW  - invasive aspergillosis
KW  - allogeneic stem cell transplantation
KW  - gene expression data
KW  - fungal infection
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165386
IS  - 7
ER  - 
TY  - JOUR
A1  - Jarius, Sven
A1  - Ruprecht, Klemens
A1  - Wildemann, Brigitte
A1  - Kuempfel, Tania
A1  - Ringelstein, Marius
A1  - Geis, Christian
A1  - Kleiter, Ingo
A1  - Kleinschnitz, Christoph
A1  - Berthele, Achim
A1  - Brettschneider, Johannes
A1  - Hellwig, Kerstin
A1  - Hemmer, Bernhard
A1  - Linker, Ralf A.
A1  - Lauda, Florian
A1  - Hayrettin, Christoph A.
A1  - Tumani, Hayrettin
A1  - Melms, Arthur
A1  - Trebst, Corinna
A1  - Stangel, Martin
A1  - Marziniak, Martin
A1  - Hoffmann, Frank
A1  - Schippling, Sven
A1  - Faiss, Jürgen H.
A1  - Neuhaus, Oliver
A1  - Ettrich, Barbara
A1  - Zentner, Christian
A1  - Guthke, Kersten
A1  - Hofstadt-van Oy, Ulrich
A1  - Reuss, Reinhard
A1  - Pellkofer, Hannah
A1  - Ziemann, Ulf
A1  - Kern, Peter
A1  - Wandinger, Klaus P.
A1  - Bergh, Florian Then
A1  - Boettcher, Tobias
A1  - Langel, Stefan
A1  - Liebetrau, Martin
A1  - Rommer, Paulus S.
A1  - Niehaus, Sabine
A1  - Münch, Christoph
A1  - Winkelmann, Alexander
A1  - Zettl, Uwe K
A1  - Metz, Imke
A1  - Veauthier, Christian
A1  - Sieb, Jörn P.
A1  - Wilke, Christian
A1  - Hartung, Hans P.
A1  - Aktas, Orhan
A1  - Paul, Friedemann
T1  - Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients
JF  - Journal of Neuroinflammation
N2  - Background: The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. 
Objective: To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. 
Methods: Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). 
Results: Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of <= 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades <= 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions >= 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF pleocytosis. Both the time to relapse and the time to diagnosis was longer if the disease started with ON (p < 0.002 and p < 0.013). Motor symptoms or tetraparesis at first myelitis and > 1 myelitis attacks in the first year were identified as possible predictors of a worse outcome.
KW  - cerebrospinal-fluid
KW  - intractable hiccup
KW  - extensiv transverse myelitis
KW  - multiple sclerosis
KW  - anti-aquaporin-4 antibody
KW  - NMO-IGG
KW  - aquaporin-4 autoantibodies
KW  - immune-response
KW  - myasthenia gravis
KW  - immunoglobulin-G
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133636
VL  - 9
IS  - 14
ER  -