Matthias Frosch

Publications of Matthias Frosch

• Transcriptome analyses in the interaction of Neisseria meningitidis with mammalian host cells.

  Authors: Biju Joseph, Matthias Frosch, Christoph Schoen, Alexandra Schubert-Unkmeir

  Methods in molecular biology (Clifton, N.J.). 01/2012; 799:267-93.

  Infectious disease research has been revolutionized by two recent developments in the field of genome biology: (1) the sequencing of the human genome as well as many pathogen genomes and (2) theInfectious disease research has been revolutionized by two recent developments in the field of genome biology: (1) the sequencing of the human genome as well as many pathogen genomes and (2) the development of high-throughput technologies including microarray technology, proteomics, and metabolomics. Microarray studies enable a deeper understanding of the genetic evolution of pathogens and investigation of the determinants of pathogenicity on a whole-genome scale. Host studies, in turn, allow for an unprecedented holistic appreciation of the complexities of host cell responses at the molecular level. In combination, host-pathogen studies allow global analysis of gene expression in the infecting bacterium as well as in the infected host cell during pathogenesis, providing a comprehensive picture of the intricacies of pathogen-host interactions. In this chapter, we briefly explain the principles underlying DNA microarrays including the major points to consider when planning and analyzing microarray experiments and we describe in detail their practical application, using the interaction of Neisseria meningitidis with human endothelial or epithelial cells as examples.

• Immunogenicity of meningococcus C vaccination in a patient with atypical hemolytic uremic syndrome (aHUS) on eculizumab therapy.

  Authors: Manuela Zlamy, Johannes Hofer, Johannes Elias, Ulrich Vogel, Matthias Frosch, Therese Jungraithmayr, Lothar Bernd Zimmerhackl, Martina Prelog

  Pediatric transplantation. 10/2011;

  Zlamy M, Hofer J, Elias J, Vogel U, Frosch M, Jungraithmayr T, Zimmerhackl LB, Prelog M. Immunogenicity of meningococcus C vaccination in a patient with atypical hemolytic uremic syndrome (aHUS) onZlamy M, Hofer J, Elias J, Vogel U, Frosch M, Jungraithmayr T, Zimmerhackl LB, Prelog M. Immunogenicity of meningococcus C vaccination in a patient with atypical hemolytic uremic syndrome (aHUS) on eculizumab therapy. Pediatr Transplantation 2011. © 2011 John Wiley & Sons A/S. Abstract:  We report successful kidney transplantation in a 10-yr-old boy with aHUS and heterozygous factor H mutation using the terminal complement inhibitor eculizumab to avoid recurrence of aHUS in the renal graft. Vaccination against meningococcus C (Men C) is essential in patients with dysfunction of the complement system, as induced by eculizumab. In our patient, we report waning SBA titers but maintenance of protective SBA titers (≥1:8) after kidney transplantation under immunosuppressive therapy with mycophenolate mofetil, tacrolimus, steroids, and eculizumab over a 27-month observational period. Our case illustrates that a humoral immune response to conjugate Men C vaccination may be mounted and maintained despite chronic renal disease, kidney transplantation, immunosuppressive drugs, and immunomodulatory therapy with eculizumab. However, it remains unclear whether serologically defined protective SBA titers mediate true protection from invasive meningococcal disease in an immunocompromised patient, particularly under treatment with a complement inhibitor. Thus, close monitoring of SBA titers seems mandatory in this patient.

• Immunochromatographic test with recombinant Em18 antigen for the follow-up study of alveolar echinococcosis.

  Authors: Yasuhito Sako, Dennis Tappe, Kenta Fukuda, Yukuharu Kobayashi, Sonoyo Itoh, Matthias Frosch, Beate Grüner, Peter Kern, Akira Ito

  Clinical and vaccine immunology : CVI. 06/2011; 18(8):1302-5.

  The performance of a rapid and simple immunochromatographic test (ICT) with recombinant Em18 (rEm18) antigen for serological follow-up of Echinococcus multilocularis infection was evaluated byThe performance of a rapid and simple immunochromatographic test (ICT) with recombinant Em18 (rEm18) antigen for serological follow-up of Echinococcus multilocularis infection was evaluated by comparison with that of an enzyme-linked immunosorbent assay (ELISA) with rEm18, using serum samples from patients who underwent surgery and/or received antiparasitic chemotherapy. The degree of Em18-band intensity on the ICT correlated highly with the absorbance value obtained by the ELISA. The kinetics of antibody levels obtained by the ICT paralleled those of the ELISA. These data suggest that the ICT has high potential as an easy-to-handle, fast, and reliable follow-up tool to monitor the status of alveolar echinococcosis in different stages.

• Immunogenicity of conjugate meningococcus C vaccine in pediatric solid organ transplant recipients.

  Authors: Manuela Zlamy, Johannes Elias, Ulrich Vogel, Matthias Frosch, Verena Jeller, Gerard Cortina, Therese Jungraithmayr, Martina Prelog

  Vaccine. 06/2011; 29(37):6163-6.

  The present study was aimed to evaluate the immunogenicity of a single dose of conjugate Meningococcus C (Men C) vaccine by analyzing the serum bactericidal antibody (SBA) titers in 10 pediatricThe present study was aimed to evaluate the immunogenicity of a single dose of conjugate Meningococcus C (Men C) vaccine by analyzing the serum bactericidal antibody (SBA) titers in 10 pediatric solid organ transplant (SOT) patients. Four patients showed a delayed immune response after 1 month, but all patients demonstrated an increase of SBA titers after vaccination. A significant decrease of SBA titers was seen after 6 months. However, all patients maintained protective SBA titers (≥1:8) despite rapidly waning titers. For patients with significantly decreasing titers, a booster dose may be discussed with close monitoring of SBA titers over time.

• Sequence analysis of serotype-specific synthesis regions II of Haemophilus influenzae serotypes c and d: evidence for common ancestry of capsule synthesis in Pasteurellaceae and Neisseria meningitidis.

  Authors: Thiên-Trí Lâm, Heike Claus, Matthias Frosch, Ulrich Vogel

  Research in microbiology. 06/2011; 162(5):483-7.

  Sequencing of yet unknown Haemophilus influenzae serotype c (Hic) and d (Hid) capsule synthesis regions II revealed four (ccs1-4) and five (dcs1-5) open reading frames, respectively. The inferredSequencing of yet unknown Haemophilus influenzae serotype c (Hic) and d (Hid) capsule synthesis regions II revealed four (ccs1-4) and five (dcs1-5) open reading frames, respectively. The inferred gene functions were in line with capsular polysaccharide structures. One or more proteins encoded by the Hic capsule synthesis region II showed similarity to Actinobacillus pleuropneumoniae serotype 1 and Actinobacillus suis K1 enzymes. Orthologues to the complete operon were observed in Actinobacillus minor strain 202, where even the gene order was conserved. Furthermore, Ccs4 was related to the capsule O-acetyltransferase of Neisseria meningitidis serogroup W-135. For the Hid locus, similarities to Hie, Mannheimia haemolytica A1 and N. meningitidis serogroup A were identified and the succession of genes was similar in the different species. The resemblance of genes and gene organization found for Hic and Hid with other species suggested horizontal gene transfer during capsule evolution across the bacterial classes.

• Transmission of Armillifer armillatus ova at snake farm, The Gambia, West Africa.

  Authors: Dennis Tappe, Michael Meyer, Anett Oesterlein, Assan Jaye, Matthias Frosch, Christoph Schoen, Nikola Pantchev

  Emerging infectious diseases. 02/2011; 17(2):251-4.

  Visceral pentastomiasis caused by Armillifer armillatus larvae was diagnosed in 2 dogs in The Gambia. Parasites were subjected to PCR; phylogenetic analysis confirmed relatedness withVisceral pentastomiasis caused by Armillifer armillatus larvae was diagnosed in 2 dogs in The Gambia. Parasites were subjected to PCR; phylogenetic analysis confirmed relatedness with branchiurans/crustaceans. Our investigation highlights transmission of infective A. armillatus ova to dogs and, by serologic evidence, also to 1 human, demonstrating a public health concern.

• Characterization of FarR as a highly specialized, growth phase-dependent transcriptional regulator in Neisseria meningitidis.

  Authors: Stephanie Schielke, Carolin Spatz, Roland Felix Schwarz, Biju Joseph, Christoph Schoen, Sabine Marita Schulz, Kerstin Hubert, Matthias Frosch, Alexandra Schubert-Unkmeir, Oliver Kurzai

  International journal of medical microbiology : IJMM. 02/2011; 301(4):325-33.

  Transcriptional regulators play an important role for the survival of Neisseria meningitidis within its human host. We have recently shown that FarR acts as transcriptional repressor of the adhesinTranscriptional regulators play an important role for the survival of Neisseria meningitidis within its human host. We have recently shown that FarR acts as transcriptional repressor of the adhesin nadA in N. meningitidis. Here, we examined the FarR regulon by microarray analyses, qRT-PCR, and electrophoretic mobility shift assays, revealing that FarR is a highly specific repressor of nadA. We demonstrate by reporter gene fusion assays that alterations of the FarR binding site within the nadA promoter are sufficient to induce transcription of nadA. Furthermore, farR expression is growth phase-dependent. The highest transcription rate was observed in the late-exponential growth phase of meningococci. Upon contact with active components of the complement system in normal human serum, expression of farR is slightly downregulated. Concluding, we present FarR as an exquisitely specialized, growth phase-dependent, possibly complement-responsive transcriptional regulator in N. meningitidis.

• Whole-genome sequence of the transformable Neisseria meningitidis serogroup A strain WUE2594.

  Authors: Christoph Schoen, Jacqueline Weber-Lehmann, Jochen Blom, Biju Joseph, Alexander Goesmann, Axel Strittmatter, Matthias Frosch

  Journal of bacteriology. 02/2011; 193(8):2064-5.

  Serogroup A meningococci are a leading cause of bacterial meningitis in children and young adults worldwide. However, the genetic basis of serogroup A strains' virulence and their epidemiologicalSerogroup A meningococci are a leading cause of bacterial meningitis in children and young adults worldwide. However, the genetic basis of serogroup A strains' virulence and their epidemiological properties remain poorly understood. Therefore, we sequenced the complete genome of the transformable Neisseria meningitidis serogroup A strain WUE2594.

• Neisseria

  Authors: Johannes Elias, Matthias Frosch, Ulrich Vogel

  01/2011: pages 559-573;

  ISBN: 978-1-5581-463-2

• Resistance to ampicillin, third-generation cephalosporins, ciprofloxacin, co-trimoxazole and azithromycin in clinical isolates of Salmonella enterica subsp. enterica from Germany: real problem or sporadic circumstance?

  Authors: Sophia Müller, Dennis Tappe, Matthias Frosch, Marianne Abele-Horn, Giuseppe Valenza

  Scandinavian journal of infectious diseases. 01/2011; 43(5):389-91.

  The objective of this study was to determine the in vitro activity of ampicillin, third-generation cephalosporins, ciprofloxacin, co-trimoxazole and azithromycin against Salmonella enterica isolates.The objective of this study was to determine the in vitro activity of ampicillin, third-generation cephalosporins, ciprofloxacin, co-trimoxazole and azithromycin against Salmonella enterica isolates. None of the isolates tested showed resistance to third-generation cephalosporins or azithromycin. The rates of resistance to ampicillin, co-trimoxazole and ciprofloxacin were 16.8%, 3.2% and 0.8%, respectively. Moreover, 7.2% of the isolates showed reduced ciprofloxacin susceptibility, but none of them harboured qnr genes. To conclude, our data show that resistance to fluoroquinolones and third-generation cephalosporins in clinical isolates found in Germany still represents a rare circumstance.

• Virulence evolution of the human pathogen Neisseria meningitidis by recombination in the core and accessory genome.

  Authors: Biju Joseph, Roland F Schwarz, Burkhard Linke, Jochen Blom, Anke Becker, Heike Claus, Alexander Goesmann, Matthias Frosch, Tobias Müller, Ulrich Vogel, Christoph Schoen

  PloS one. 01/2011; 6(4):e18441.

  Neisseria meningitidis is a naturally transformable, facultative pathogen colonizing the human nasopharynx. Here, we analyze on a genome-wide level the impact of recombination on gene-complementNeisseria meningitidis is a naturally transformable, facultative pathogen colonizing the human nasopharynx. Here, we analyze on a genome-wide level the impact of recombination on gene-complement diversity and virulence evolution in N. meningitidis. We combined comparative genome hybridization using microarrays (mCGH) and multilocus sequence typing (MLST) of 29 meningococcal isolates with computational comparison of a subset of seven meningococcal genome sequences. We found that lateral gene transfer of minimal mobile elements as well as prophages are major forces shaping meningococcal population structure. Extensive gene content comparison revealed novel associations of virulence with genetic elements besides the recently discovered meningococcal disease associated (MDA) island. In particular, we identified an association of virulence with a recently described canonical genomic island termed IHT-E and a differential distribution of genes encoding RTX toxin- and two-partner secretion systems among hyperinvasive and non-hyperinvasive lineages. By computationally screening also the core genome for signs of recombination, we provided evidence that about 40% of the meningococcal core genes are affected by recombination primarily within metabolic genes as well as genes involved in DNA replication and repair. By comparison with the results of previous mCGH studies, our data indicated that genetic structuring as revealed by mCGH is stable over time and highly similar for isolates from different geographic origins. Recombination comprising lateral transfer of entire genes as well as homologous intragenic recombination has a profound impact on meningococcal population structure and genome composition. Our data support the hypothesis that meningococcal virulence is polygenic in nature and that differences in metabolism might contribute to virulence.

• Characterization of extended-spectrum beta-lactamases and qnr plasmid-mediated quinolone resistance in German isolates of Enterobacter species.

  Authors: Sophia Müller, Anett Oesterlein, Matthias Frosch, Marianne Abele-Horn, Giuseppe Valenza

  Microbial drug resistance (Larchmont, N.Y.). 12/2010; 17(1):99-103.

  The objective of this study was to characterize the antimicrobial resistance patterns of 100 clinical isolates of Enterobacter spp. with special regard to the occurrence of extended-spectrumThe objective of this study was to characterize the antimicrobial resistance patterns of 100 clinical isolates of Enterobacter spp. with special regard to the occurrence of extended-spectrum beta-lactamases (ESBLs) and plasmid-mediated quinolone resistance by qnr-determinants. The rate of ESBL- and qnr-positive isolates was 7% and 14%, respectively. Thirteen isolates harbored a qnrA1, and a further isolate harbored a qnrB4 gene. Moreover, qnr-determinants were significantly associated with ESBL-expression. No carbapeneme or tigecycline resistance was detected in the collective tested. To conclude, these data confirm the increase of multiple antimicrobial resistance mechanisms in Enterobacter spp.

• Pathogen-specific DNA enrichment does not increase sensitivity of PCR for diagnosis of invasive aspergillosis in neutropenic patients.

  Authors: Jan Springer, Juergen Loeffler, Werner Heinz, Hannes Schlossnagel, Marc Lehmann, Oliver Morton, Thomas R Rogers, Corinna Schmitt, Matthias Frosch, Hermann Einsele, Oliver Kurzai

  Journal of clinical microbiology. 12/2010; 49(4):1267-73.

  PCR assays designed for the diagnosis of invasive aspergillosis (IA) in high-risk patients have to detect minute amounts of target DNA to reach sufficient analytical sensitivity to be of clinicalPCR assays designed for the diagnosis of invasive aspergillosis (IA) in high-risk patients have to detect minute amounts of target DNA to reach sufficient analytical sensitivity to be of clinical use. This prospective study assessed the use of a novel strategy for selective pathogen DNA enrichment for enhancing the performance of diagnostic PCR in a direct comparison with a highly sensitive in-house quantitative PCR (qPCR) assay and the galactomannan enzyme-linked immunosorbent assay (ELISA). Surprisingly, and in contrast to experience with other patient groups, the novel protocol for selective pathogen DNA enrichment did not enhance but instead significantly impaired sensitivity. This could be explained by the small amounts of host DNA in the specimens, which were derived mostly from severely neutropenic patients. In the qPCR assay, positive samples required an average of 43.5 amplification cycles (range, 39.2 to 50) for detection in the in-house PCR. Repetitive testing of selected samples showed test positivity to be variable, most likely due to the small amounts of target DNA. Despite this, the in-house protocol proved helpful in the diagnosis of IA, detecting 2 out of 3 patients with probable IA and 10 out of 19 patients with possible IA. Our results underline the necessity for diagnostic PCR protocols that help diagnose IA to be highly sensitive and show that selective pathogen DNA enrichment using affinity purification may not be useful in severely neutropenic patients.

• Resistance to tobramycin and colistin in isolates of Pseudomonas aeruginosa from chronically colonized patients with cystic fibrosis under antimicrobial treatment.

  Authors: Giuseppe Valenza, Kerstin Radike, Christoph Schoen, Stephan Horn, Anett Oesterlein, Matthias Frosch, Marianne Abele-Horn, Helge Hebestreit

  Scandinavian journal of infectious diseases. 12/2010; 42(11-12):885-9.

  Tobramycin and colistin represent 2 standard antimicrobial agents in the treatment of cystic fibrosis (CF) patients who are chronically colonized with Pseudomonas aeruginosa. In this study, weTobramycin and colistin represent 2 standard antimicrobial agents in the treatment of cystic fibrosis (CF) patients who are chronically colonized with Pseudomonas aeruginosa. In this study, we determined the rate of resistance to tobramycin and colistin in 1844 isolates of P. aeruginosa obtained from 22 CF patients under alternate therapy with inhaled tobramycin and colistin. Resistance to tobramycin was observed in 27.5% of isolates. In contrast, all isolates were susceptible to colistin. Molecular typing of selected isolates suggested that only 1 clone occurred over time in each patient. To conclude, resistance to tobramycin in P. aeruginosa isolates from CF patients under antimicrobial therapy may occur while colistin resistance remains uncommon.

• New diagnostic PCR for Haemophilus influenzae serotype e based on the cap locus of strain ATCC 8142.

  Authors: Thiên-Trí Lâm, Johannes Elias, Matthias Frosch, Ulrich Vogel, Heike Claus

  International journal of medical microbiology : IJMM. 10/2010; 301(2):176-9.

  A new PCR protocol for molecular typing of Haemophilus influenzae serotype e (Hie) was developed. To this end, the sequence of the cap region II of Hie strain ATCC8142 was identified, which was >99%A new PCR protocol for molecular typing of Haemophilus influenzae serotype e (Hie) was developed. To this end, the sequence of the cap region II of Hie strain ATCC8142 was identified, which was >99% identical to the recently published sequence of Hie isolate 274. The PCR using primer pair TTL63/TTL64 amplifies an internal 592-bp fragment of ecs4, an e-specific capsule synthesis gene, in 40 of 40 Hie strains. Of all non-Hie strains, there were no false positives. False-negative results of the PCR proposed by Falla et al. (1994) are explained by single nucleotide insertions in the primer sequences.

• Comparative genome biology of a serogroup B carriage and disease strain supports a polygenic nature of meningococcal virulence.

  Authors: Biju Joseph, Susanne Schneiker-Bekel, Anja Schramm-Glück, Jochen Blom, Heike Claus, Burkhard Linke, Roland F Schwarz, Anke Becker, Alexander Goesmann, Matthias Frosch, Christoph Schoen

  Journal of bacteriology. 10/2010; 192(20):5363-77.

  Neisseria meningitidis serogroup B strains are responsible for most meningococcal cases in the industrialized countries, and strains belonging to the clonal complex ST-41/44 are among the mostNeisseria meningitidis serogroup B strains are responsible for most meningococcal cases in the industrialized countries, and strains belonging to the clonal complex ST-41/44 are among the most prevalent serogroup B strains in carriage and disease. Here, we report the first genome and transcriptome comparison of a serogroup B carriage strain from the clonal complex ST-41/44 to the serogroup B disease strain MC58 from the clonal complex ST-32. Both genomes are highly colinear, with only three major genome rearrangements that are associated with the integration of mobile genetic elements. They further differ in about 10% of their gene content, with the highest variability in gene presence as well as gene sequence found for proteins involved in host cell interactions, including Opc, NadA, TonB-dependent receptors, RTX toxin, and two-partner secretion system proteins. Whereas housekeeping genes coding for metabolic functions were highly conserved, there were considerable differences in their expression pattern upon adhesion to human nasopharyngeal cells between both strains, including differences in energy metabolism and stress response. In line with these genomic and transcriptomic differences, both strains also showed marked differences in their in vitro infectivity and in serum resistance. Taken together, these data support the concept of a polygenic nature of meningococcal virulence comprising differences in the repertoire of adhesins as well as in the regulation of metabolic genes and suggest a prominent role for immune selection and genetic drift in shaping the meningococcal genome.

• Evaluation of one- and two-color gene expression arrays for microbial comparative genome hybridization analyses in routine applications.

  Authors: Roland Schwarz, Biju Joseph, Gabriele Gerlach, Anja Schramm-Glück, Kathrin Engelhard, Matthias Frosch, Tobias Müller, Christoph Schoen

  Journal of clinical microbiology. 09/2010; 48(9):3105-10.

  DNA microarray technology has already revolutionized basic research in infectious diseases, and whole-genome sequencing efforts have allowed for the fabrication of tailor-made spotted microarrays forDNA microarray technology has already revolutionized basic research in infectious diseases, and whole-genome sequencing efforts have allowed for the fabrication of tailor-made spotted microarrays for an increasing number of bacterial pathogens. However, the application of microarrays in diagnostic microbiology is currently hampered by the high costs associated with microarray experiments and the specialized equipment needed. Here, we show that a thorough bioinformatic postprocessing of the microarray design to reduce the amount of unspecific noise also allows the reliable use of spotted gene expression microarrays for gene content analyses. We further demonstrate that the use of only single-color labeling to halve the costs for dye-labeled nucleotides results in only a moderate decrease in overall specificity and sensitivity. Therefore, gene expression microarrays using only single-color labeling can also reliably be used for gene content analyses, thus reducing the costs for potential routine applications such as genome-based pathogen detection or strain typing.

• Immunoglobulin G subclass responses to recombinant Em18 in the follow-up of patients with alveolar echinococcosis in different clinical stages.

  Authors: Dennis Tappe, Yasuhito Sako, Sonoyo Itoh, Matthias Frosch, Beate Grüner, Peter Kern, Akira Ito

  Clinical and vaccine immunology : CVI. 06/2010; 17(6):944-8.

  In this study, we compared the sequential responses of immunoglobulin G (IgG) subclasses to the diagnostic antigen Em18 in sera from patients with alveolar echinococcosis. A total of 225 sera from 36In this study, we compared the sequential responses of immunoglobulin G (IgG) subclasses to the diagnostic antigen Em18 in sera from patients with alveolar echinococcosis. A total of 225 sera from 36 patients at different clinical stages according to the WHO-PNM staging system were tested. The antibody responses were measured for cohorts with resected and unresected parasitic lesions by enzyme-linked immunosorbent assays (ELISA). Total IgG and, to a lesser extent, IgG4 antibody levels against Em18 correlated with all PNM stages before treatment, whereas levels of IgG2 were low and IgG3 was undetectable. Antibody kinetics, however, depended on the treatment rather than on the PNM stage. For some patients, after curative surgery, IgG1 antibodies dropped below the cutoff earlier than other antibodies, followed by total IgG and IgG4 within 18 months. For some patients with recurrences after surgery, IgG1 and IgG4 reappeared, whereas patients with unresectable lesions but stable disease showed steady declines in the levels of all antibodies, and IgG1 became undetectable in some patients. Additional testing of IgE responses to Em18 showed constantly low levels at all stages and in all cohorts.

• First survey of metallo-beta-lactamases in clinical isolates of Pseudomonas aeruginosa in a German university hospital.

  Authors: Giuseppe Valenza, Biju Joseph, Johannes Elias, Heike Claus, Anett Oesterlein, Kathrin Engelhardt, Doris Turnwald, Matthias Frosch, Marianne Abele-Horn, Christoph Schoen

  Antimicrobial agents and chemotherapy. 05/2010; 54(8):3493-7.

  A total of 489 clinical isolates of Pseudomonas aeruginosa was investigated for metallo-beta-lactamase (MBL) production. Molecular analysis detected a blaVIM-1 gene in the chromosome of one isolateA total of 489 clinical isolates of Pseudomonas aeruginosa was investigated for metallo-beta-lactamase (MBL) production. Molecular analysis detected a blaVIM-1 gene in the chromosome of one isolate and a blaVIM-2 gene carried on the plasmid in seven isolates. Moreover, we showed that an initial screening by combined susceptibility testing of imipenem and ceftazidime followed by a confirmatory EDTA combination disk test represents a valid alternative to the molecular investigation of MBL genes, making MBL detection possible in routine diagnostic laboratories.

• Comparison of two interferon-γ release assays and tuberculin skin test for detecting latent tuberculosis in patients with immune-mediated inflammatory diseases

  Authors: Stefan Kleinert, Oliver Kurzai, Johannes Elias, K. Marten, C. Engelke, M. Feuchtenberger, J. Sandstede, Matthias Frosch, H-P. Tony, C. Kneitz

  Annals of the Rheumatic Diseases. 04/2010; 69::782 -784.