Tobias Rogosch

Publications (12) View all

• Article: T(H)17 Cell Frequency in Peripheral Blood from Children with Allergic Asthma Correlates with the Level of Asthma Control.

  Sebastian Kerzel, Jana Dehne, Tobias Rogosch, Bianca Schaub, Rolf F Maier, Michael Zemlin
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  ABSTRACT: Here we show that the frequency of T(H)17 cells (CD3(+)CD4(+)CD161(+)CCR6(+) lymphocytes) is increased in peripheral blood of children with allergic asthma. Moreover, we found a significant relationship between the frequency of T(H)17 cells and level of asthma control, with reduced asthma control correlated with a higher proportion of T(H)17 cells.
  The Journal of pediatrics 08/2012; · 4.02 Impact Factor
• Source

  Available from: Tobias Rogosch

  Article: Immunoglobulin analysis tool: a novel tool for the analysis of human and mouse heavy and light chain transcripts.

  Tobias Rogosch, Sebastian Kerzel, Kam Hon Hoi, Zhixin Zhang, Rolf F Maier, Gregory C Ippolito, Michael Zemlin
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  ABSTRACT: Sequence analysis of immunoglobulin (Ig) heavy and light chain transcripts can refine categorization of B cell subpopulations and can shed light on the selective forces that act during immune responses or immune dysregulation, such as autoimmunity, allergy, and B cell malignancy. High-throughput sequencing yields Ig transcript collections of unprecedented size. The authoritative web-based IMGT/HighV-QUEST program is capable of analyzing large collections of transcripts and provides annotated output files to describe many key properties of Ig transcripts. However, additional processing of these flat files is required to create figures, or to facilitate analysis of additional features and comparisons between sequence sets. We present an easy-to-use Microsoft(®) Excel(®) based software, named Immunoglobulin Analysis Tool (IgAT), for the summary, interrogation, and further processing of IMGT/HighV-QUEST output files. IgAT generates descriptive statistics and high-quality figures for collections of murine or human Ig heavy or light chain transcripts ranging from 1 to 150,000 sequences. In addition to traditionally studied properties of Ig transcripts - such as the usage of germline gene segments, or the length and composition of the CDR-3 region - IgAT also uses published algorithms to calculate the probability of antigen selection based on somatic mutational patterns, the average hydrophobicity of the antigen-binding sites, and predictable structural properties of the CDR-H3 loop according to Shirai's H3-rules. These refined analyses provide in-depth information about the selective forces acting upon Ig repertoires and allow the statistical and graphical comparison of two or more sequence sets. IgAT is easy to use on any computer running Excel(®) 2003 or higher. Thus, IgAT is a useful tool to gain insights into the selective forces and functional properties of small to extremely large collections of Ig transcripts, thereby assisting a researcher to mine a data set to its fullest.
  Frontiers in immunology. 01/2012; 3:176.
• Article: Plasmapheresis prior to omalizumab administration in a 15-year-old boy with severe asthma and very high IgE levels: sustained effect over 2 years.

  S Kerzel, M Zemlin, T Rogosch, M Ollert, H Renz, G Klaus, R F Maier
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  ABSTRACT: Anti-IgE therapy with omalizumab is an innovative therapy option in patients with severe allergic asthma. However, many patients are excluded from this treatment due to very high serum IgE levels which lie above the weight-dependent cut-off for a reasonable omalizumab administration (700 kU/l). We sought to evaluate whether a preceding plasma exchange is suitable to establish the starting basis for a subsequent anti-IgE therapy in a 15 year-old boy with steroid-resistant unstable allergic asthma whose pretreatment serum IgE levels ranged between 3 000 and 8 000 kU/l. Our aim was to create a period with relatively low IgE serum concentrations, which could be overridden by a high dose of omalizumab. 3 sessions of plasmapheresis were performed and 3×3 000 ml plasma were exchanged against albumin solution. We removed an absolute amount of 8 650 kU total IgE. During plasmapheresis, serum IgE levels markedly declined and fell below 500 kU/l. Immediately after the third plasma exchange, we started omalizumab therapy. As expected, total IgE levels began to rise again upon cessation of plasmapheresis, and after 2 months the pre-treatment values were reached. In contrast, serum concentrations of free IgE remained stable on a level of about 80 kU/l during the whole observation period. During this period, the boy displayed a considerable improvement of asthma control and an increase in quality of life. In addition, his previously poor lung function normalized. Plasmapheresis prior to omalizumab administration is suitable to temporarily reduce grossly elevated serum IgE levels and might facilitate anti-IgE therapy in selected patients previously considered not suitable for this therapy.
  Klinische Pädiatrie 11/2011; 223(6):356-9. · 1.77 Impact Factor
• Article: IgA Response in Preterm Neonates Shows Little Evidence of Antigen-Driven Selection.

  Tobias Rogosch, Sebastian Kerzel, Katharina Hoß, Gabriele Hoersch, Cosima Zemlin, Matthias Heckmann, Claudia Berek, Harry W Schroeder, Rolf F Maier, Michael Zemlin
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  ABSTRACT: After birth, contact to environmental Ags induces the production of IgA, which represents a first line of defense for the neonate. We sought to characterize the maturation of the repertoire of IgA H chain transcripts in circulating blood B cells during human ontogeny. We found that IgA H chain transcripts were present in cord blood as early as 27 wk of gestation and that the restrictions of the primary Ab repertoire (IgM) persisted in the IgA repertoire. Thus, B cells harboring more "mature" V(H) regions were not preferred for class switch to IgA. Preterm and term neonates expressed a unique IgA repertoire, which was characterized by short CDR-H3 regions, preference of the J(H) proximal D(H)7-27 gene segment, and very few somatic mutations. During the first postnatal months, these restrictions were slowly released. Preterm birth did not measurably accelerate the maturation of the IgA repertoire. At a postconceptional age of 60 wk, somatic mutation frequency of IgA H chain transcripts reached 25% of the adult values but still showed little evidence of Ag-driven selection. These results indicate that similar to IgG, the IgA repertoire expands in a controlled manner after birth. Thus, the IgA repertoire of the newborn has distinctive characteristics that differ from the adult IgA repertoire. These observations might explain the lower affinity and specificity of neonatal IgA Abs, which could contribute to a higher susceptibility to infections and altered responses to vaccinations, but might also prevent the development of autoimmune and allergic diseases.
  The Journal of Immunology 10/2012; · 5.79 Impact Factor
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  Available from: Tobias Rogosch

  Article: Antibody repertoires in humanized NOD-scid-IL2Rγ(null) mice and human B cells reveals human-like diversification and tolerance checkpoints in the mouse.

  Gregory C Ippolito, Kam Hon Hoi, Sai T Reddy, Sean M Carroll, Xin Ge, Tobias Rogosch, Michael Zemlin, Leonard D Shultz, Andrew D Ellington, Carla L Vandenberg, George Georgiou
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  ABSTRACT: Immunodeficient mice reconstituted with human hematopoietic stem cells enable the in vivo study of human hematopoiesis. In particular, NOD-scid-IL2Rγ(null) engrafted mice have been shown to have reasonable levels of T and B cell repopulation and can mount T-cell dependent responses; however, antigen-specific B-cell responses in this model are generally poor. We explored whether developmental defects in the immunoglobulin gene repertoire might be partly responsible for the low level of antibody responses in this model. Roche 454 sequencing was used to obtain over 685,000 reads from cDNA encoding immunoglobulin heavy (IGH) and light (IGK and IGL) genes isolated from immature, naïve, or total splenic B cells in engrafted NOD-scid-IL2Rγ(null) mice, and compared with over 940,000 reads from peripheral B cells of two healthy volunteers. We find that while naïve B-cell repertoires in humanized mice are chiefly indistinguishable from those in human blood B cells, and display highly correlated patterns of immunoglobulin gene segment use, the complementarity-determining region H3 (CDR-H3) repertoires are nevertheless extremely diverse and are specific for each individual. Despite this diversity, preferential D(H)-J(H) pairings repeatedly occur within the CDR-H3 interval that are strikingly similar across all repertoires examined, implying a genetic constraint imposed on repertoire generation. Moreover, CDR-H3 length, charged amino-acid content, and hydropathy are indistinguishable between humans and humanized mice, with no evidence of global autoimmune signatures. Importantly, however, a statistically greater usage of the inherently autoreactive IGHV4-34 and IGKV4-1 genes was observed in the newly formed immature B cells relative to naïve B or total splenic B cells in the humanized mice, a finding consistent with the deletion of autoreactive B cells in humans. Overall, our results provide evidence that key features of the primary repertoire are shaped by genetic factors intrinsic to human B cells and are principally unaltered by differences between mouse and human stromal microenvironments.
  PLoS ONE 01/2012; 7(4):e35497. · 4.09 Impact Factor