Heimo Breiteneder

Medical University of Vienna, Wien, Vienna, Austria

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Publications (277)1375.12 Total impact

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    ABSTRACT: Fish allergy is associated with moderate to severe IgE-mediated reactions to the calcium binding parvalbumins present in fish muscle. Allergy to multiple fish species is caused by parvalbumin-specific cross-reactive IgE recognizing conserved epitopes. In this study, we aimed to produce cross-reactive single chain variable fragment (scFv) antibodies for the detection of parvalbumins in fish extracts and the identification of IgE epitopes. Parvalbumin-specific phage clones were isolated from the human ETH-2 phage display library by three rounds of biopanning either against cod parvalbumin or by sequential biopanning against cod (Gad m 1), carp (Cyp c 1) and rainbow trout (Onc m 1) parvalbumins. While biopanning against Gad m 1 resulted in the selection of clones specific exclusively for Gad m 1, the second approach resulted in the selection of clones cross-reacting with all three parvalbumins. Two clones, scFv-gco9 recognizing all three parvalbumins, and scFv-goo8 recognizing only Gad m 1 were expressed in the E. coli non-suppressor strain HB2151 and purified from the periplasm. scFv-gco9 showed highly selective binding to parvalbumins in processed fish products such as breaded cod sticks, fried carp and smoked trout in Western blots. In addition, the scFv-gco9-AP produced as alkaline phosphatase fusion protein, allowed a single-step detection of the parvalbumins. In competitive ELISA, scFv-gco9 was able to inhibit binding of IgE from fish allergic patients' sera to all three β-parvalbumins by up to 80%, whereas inhibition by scFv-goo8 was up to 20%. 1H/15N HSQC NMR analysis of the rGad m 1:scFv-gco9 complex showed participation of amino acid residues conserved among these three parvalbumins explaining their cross-reactivity on a molecular level. In this study, we have demonstrated an approach for the selection of cross-reactive parvalbumin-specific antibodies that can be used for allergen detection and for mapping of conserved epitopes.
    PLoS ONE 11/2015; 10(11):e0142625. DOI:10.1371/journal.pone.0142625 · 3.23 Impact Factor
  • Mei Xue · Lin Yang · Da-zhuo Shi · Christian Radauer · Heimo Breiteneder · Yan Ma ·

    Chinese Journal of Integrative Medicine 10/2015; 21(10):772-777. DOI:10.1007/s11655-015-2311-2 · 1.22 Impact Factor

  • The Journal of allergy and clinical immunology 07/2015; DOI:10.1016/j.jaci.2015.05.025 · 11.48 Impact Factor
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    ABSTRACT: Dendritic cells (DCs) are sentinels of the immune system for antigen recognition and uptake, as well as presentation to naïve T cells for stimulation or priming. Internalization and endocytic degradation of allergens by DCs are important steps required for T-cell priming. In the current study we investigated binding and internalization of purified recombinant non-glycosylated grass pollen allergen, Phl p 5, and natural non-specific lipid transfer protein from sunflower, SF-nsLTP to human monocyte derived dendritic cells (MoDCs). Colocalization of Phl p 5 with low affinity (CD23) or high affinity receptor (FcεRI) was investigated by immunofluorescence staining. Likewise, localization of the allergens in early (EE) and late endosomes (LE) was detected by co-staining for early endosome antigen (EEA1) and lysosomal-associated membrane protein 1 (LAMP1). In our experimental setting we could demonstrate that Phl p 5 as well as SF-nsLTP bound to MoDCs from both, grass pollen allergic and non-allergic individuals. Competitive allergen uptake experiments demonstrated non-preferential and simultaneous uptake of Phl p 5 and SF-nsLTP by MoDCs. No overlap of signals from Phl p 5 and CD23 or FcεRI was detectable, excluding IgE-mediated uptake for this allergen. Both allergens, Phl p 5 and SF-nsLTP, were localized in early and late endosomes. The present study applied a set of methods to assess the allergen uptake by MoDCs in an in vitro model. No qualitative and quantitative differences in the allergen uptake of both, Phl p 5 and SF-nsLTP were detected in single and competitive assays. Copyright © 2015. Published by Elsevier B.V.
    Journal of immunological methods 06/2015; 126. DOI:10.1016/j.jim.2015.06.001 · 1.82 Impact Factor
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    ABSTRACT: Chondroitin sulfate proteoglycan 4 (CSPG4), a highly immunogenic melanoma tumor antigen, is a potential target for antibody-based immunotherapy. The mechanism by which CSPG4 affects melanoma progression is only partly understood, in particular the involvement of other receptor tyrosine kinases and the tumor microenvironment. We have previously reported on a mimotope-based vaccine against CSPG4 in a human melanoma xenograft model that resulted in reduction of tumor growth. Herein we describe the influence of hypoxia on the response to polyclonal anti-CSPG4-antibodies induced by this vaccine in combination with the BRAF inhibitor vemurafenib to enhance therapeutic efficacy by simultaneously targeting multiple signaling pathways. Melanoma cells were treated with polyclonal anti-CSPG4-antibodies and vemurafenib. Proliferation, migration and invasion were evaluated in a real-time setting in the impedance-based x-CELLigence® system. Western blotting and quantitative PCR arrays were used to determine protein and mRNA expression of hypoxia inducible factor 1α (HIF1α), carbonic anhydrase IX (CAIX) and signaling pathway proteins. A melanoma xenograft model was used to detect HIF1α and CAIX expression in vivo. Hypoxia enhanced the antiproliferative response to vemurafenib. The migration and invasion capacities of vemurafenib-treated melanoma cells were increased, in spite of vemurafenib-decreased expression of HIF1α and CAIX. Polyclonal anti-CSPG4-antibodies reduced the Transwell migration of vemurafenib-treated, BRAF V600E-mutant and CSPG4-expressing melanoma cells in hypoxia. This was associated with the downregulation of phosphorylated AKT, a kinase contributing to tumor cell migration. Our results highlight CSPG4 as a potential target for modulating treatment resistance to vemurafenib induced by the hypoxic microenvironment.
    International Journal of Oncology 05/2015; 47(1). DOI:10.3892/ijo.2015.3010 · 3.03 Impact Factor

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    ABSTRACT: Peanut allergy develops after primary sensitization to peanut allergens and/or IgE cross-sensitization with homologous allergens from various plants. Therefore, heterogeneous patterns of sensitization to individual peanut allergens are observed in different countries. The aim of this study was to examine the IgE sensitization patterns of Austrian peanut-allergic patients. Sera from 65 peanut-allergic patients and 20 peanut-tolerant atopics were obtained in four Austrian allergy clinics. Sensitization patterns against peanut allergens Ara h 1-3, 6, 8 and 9 were identified by ImmunoCAP and ImmunoCAP ISAC. Austrian peanut-allergic patients were sensitized to Ara h 2 and 6 (71%), followed by Ara h 1 (62%), Ara h 8 (45%), Ara h 3 (35%) and Ara h 9 (11%). All sera containing Ara h 2-specific IgE were also positive for Ara h 6, with Ara h 6-specific IgE levels significantly (p < 0.05) higher compared with Ara h 2. Twelve percent displayed IgE reactivity exclusively to Ara h 8. Peanut extract and Ara h 8 showed low diagnostic specificities of 25 and 10%, respectively. The other peanut allergens showed 100% specificity. Diagnostic sensitivities determined by ImmunoCAP ISAC and ImmunoCAP were highly similar for Ara h 2, 3 and 8. The majority of symptomatic peanut-allergic patients are sensitized to Ara h 2 and Ara h 6. In peanut-symptomatic patients with additional birch pollen allergy, other peanut allergens, especially Ara h 8, should be tested when IgE reactivity to Ara h 2 is absent. © 2015 S. Karger AG, Basel.
    International Archives of Allergy and Immunology 02/2015; 166(1):13-24. DOI:10.1159/000371422 · 2.67 Impact Factor
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    Journal of Allergy and Clinical Immunology 02/2015; 135(2):AB32. DOI:10.1016/j.jaci.2014.12.1035 · 11.48 Impact Factor
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    ABSTRACT: Dendritic cells play a fundamental role in shaping the immune response to allergens. The events that lead to allergic sensitization or tolerance induction during the interaction of the major birch pollen allergen Bet v 1 and dendritic cells are not very well studied. Here, we analyzed the uptake of Bet v 1 and the cross-reactive celery allergen Api g 1 by immature monocyte-derived dendritic cells (iMoDCs) of allergic and normal donors. In addition, we characterized the allergen-triggered intracellular signaling and transcriptional events. Uptake kinetics, competitive binding, and internalization pathways of labeled allergens by iMoDCs were visualized by live-cell imaging. Surface-bound IgE was detected by immunofluorescence microscopy and flow cytometry. Allergen- and IgE-induced gene expression of early growth response genes and Th1 and Th2 related cytokines and chemokines were analyzed by real-time PCR. Phosporylation of signaling kinases was analyzed by Western blot. Internalization of Bet v 1 by iMoDCs of both donor groups, likely by receptor-mediated caveolar endocytosis, followed similar kinetics. Bet v 1 outcompeted Api g 1 in cell surface binding and uptake. MoDCs of allergic and healthy donors displayed surface-bound IgE and showed a pronounced upregulation of Th2 cytokine- and NFκB-dependent genes upon non-specific Fcε receptor cross-linking. In contrast to these IgE-mediated responses, Bet v 1-stimulation increased transcript levels of the Th2 cytokines IL-4 and IL-13 but not of NFκB-related genes in MoDCs of BP allergic donors. Cells of healthy donors were either unresponsive or showed elevated mRNA levels of Th1-promoting chemokines. Moreover, Bet v 1 was able to induce Erk1/2 and p38 MAPK activation in BP allergics but only a slight p38 activation in normal donors. In conclusion, our data indicate that Bet v 1 favors the activation of a Th2 program only in DCs of BP allergic individuals.
    PLoS ONE 01/2015; 10(1):e0117904. DOI:10.1371/journal.pone.0117904 · 3.23 Impact Factor
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    ABSTRACT: We present an infrared biopsymeter to assist pathologists in the diagnosis of melanoma presence in skin biopsies. The designed and realized system combines the features of visual inspection and physical sensing to reduce false positives and false negatives occurring during standard histopathological analyses. The biopsymeter determines the CH2-stretch ratio by infrared absorbance measurements of skin biopsies. Investigations conducted with the biopsymeter shows that malignant melanomas and melanoma metastases have higher CH2-stretch ratio values compared to healthy skin tissues.
  • Merima Bublin · Heimo Breiteneder ·
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    ABSTRACT: Peanut allergy is an IgE-mediated, persisting immune disorder that is of major concern worldwide. Currently, no routine immunotherapy is available to treat this often severe and sometimes fatal food allergy. Traditional subcutaneous allergen immunotherapy with crude peanut extracts has proven not feasible due to the high risk of severe systemic side effects. The allergen-specific approaches under preclinical and clinical investigation comprise subcutaneous, oral, sublingual and epicutaneous immunotherapy with whole-peanut extracts as well as applications of hypoallergenic peanut allergens or T cell epitope peptides. Allergen-nonspecific approaches include monoclonal anti-IgE antibodies, TCM herbal formulations and Toll-like receptor 9-based immunotherapy. The potential of genetically engineered plants with reduced allergen levels is being explored as well as the beneficial influence of lactic acid bacteria and soybean isoflavones on peanut allergen-induced symptoms. Although the underlying mechanisms still need to be elucidated, several of these strategies hold great promise. It can be estimated that individual strategies or a combination thereof will result in a successful immunotherapy regime for peanut-allergic individuals within the next decade. © 2014 S. Karger AG, Basel.
    International Archives of Allergy and Immunology 12/2014; 165(3):179-194. DOI:10.1159/000369340 · 2.67 Impact Factor
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    ABSTRACT: Beta-parvalbumins from different fish species have been identified as the main elicitors of IgE-mediated reactions in fish-allergic individuals. Here, we report for the first time the NMR determination of the structure and dynamics of the major Atlantic cod (Gadus morhua) allergen Gad m 1 and compare them with other known parvalbumins. Although the Gad m 1 structure and accessibility of putative IgE epitopes are similar to parvalbumins in mackerel and carp, the charge distribution at the putative epitopes is different. The determination of the Gad m 1 structure contributes to a better understanding of cross-reactivity among fish parvalbumins. In addition, the high-pressure NMR and temperature variation experiments revealed the important contribution of the AB motif and other regions to the protein folding. This structural information could assist the future identification of hot spots for targeted mutations to develop hypoallergenic Ca2+-free forms for potential use in immunotherapy. © Proteins 2014;. © 2014 Wiley Periodicals, Inc.
    Proteins Structure Function and Bioinformatics 11/2014; 82(11). DOI:10.1002/prot.24664 · 2.63 Impact Factor
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    ABSTRACT: Background Birch pollen-associated plant food allergy is caused by Bet v 1-specific IgE, but presence of cross-reactive IgE to related allergens does not predict food allergy. The role of other immunoglobulin isotypes in the birch pollen-plant food syndrome has not been investigated in detail.Methods Bet v 1-sensitised birch pollen-allergic patients (n = 35) were diagnosed for food allergy by standardised interviews, skin prick tests, prick-to-prick tests and ImmunoCAP. Concentrations of allergen-specific IgE, IgG1, IgG4 and IgA to seven Bet v 1-related food allergens were determined by ELISA.ResultsBet v 1, Cor a 1, Mal d 1 and Pru p 1 bound IgE from all and IgG4 and IgA from the majority of sera. Immunoglobulins to Gly m 4, Vig r 1 and Api g 1.01 were detected in less than 65% of the sera. No significant correlation was observed between plant food allergy and increased or reduced levels of IgE, IgG1, IgG4 or IgA specific for most Bet v 1-related allergens. Api g 1-specific IgE was significantly (p = 0.01) elevated in celeriac-allergic compared to celeriac-tolerant patients. Likewise, frequencies of IgE (71% versus 15%; p = 0.01) and IgA (86% versus 38%; p = 0.04) binding to Api g 1.01 were increased.Conclusion Measurements of allergen-specific immunoglobulins are not suitable for diagnosing Bet v 1-mediated plant food allergy to hazelnut and Rosaceae fruits. In contrast, IgE and IgA to the distantly related allergen Api g 1 correlate with allergy to celeriac.This article is protected by copyright. All rights reserved.
    Allergy 10/2014; 70(1). DOI:10.1111/all.12534 · 6.03 Impact Factor

  • Cancer Research 10/2014; 74(19 Supplement):508-508. DOI:10.1158/1538-7445.AM2014-508 · 9.33 Impact Factor
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    Merima Bublin · Thomas Eiwegger · Heimo Breiteneder ·
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    ABSTRACT: Allergic sensitization is a multifactorial process that is not only influenced by the allergen and its biological function per se but also by other small molecular compounds, such as lipids, that are directly bound as ligands by the allergen or are present in the allergen source. Several members of major allergen families bind lipid ligands through hydrophobic cavities or electrostatic or hydrophobic interactions. These allergens include certain seed storage proteins, Bet v 1-like and nonspecific lipid transfer proteins from pollens and fruits, certain inhalant allergens from house dust mites and cockroaches, and lipocalins. Lipids from the pollen coat and furry animals and the so-called pollen-associated lipid mediators are codelivered with the allergens and can modulate the immune responses of predisposed subjects by interacting with the innate immune system and invariant natural killer T cells. In addition, lipids originating from bacterial members of the pollen microbiome contribute to the outcome of the sensitization process. Dietary lipids act as adjuvants and might skew the immune response toward a TH2-dominated phenotype. In addition, the association with lipids protects food allergens from gastrointestinal degradation and facilitates their uptake by intestinal cells. These findings will have a major influence on how allergic sensitization will be viewed and studied in the future.
    Journal of Allergy and Clinical Immunology 05/2014; 134(3). DOI:10.1016/j.jaci.2014.04.015 · 11.48 Impact Factor
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    ABSTRACT: SINI TANG (SNT) IS A TRADITIONAL CHINESE HERBAL FORMULA CONSISTING OF FOUR DIFFERENT HERBS: the root of Aconitum carmichaelii, the bark of Cinnamomum cassia, the rhizome of Zingiber officinale, and the root of Glycyrrhiza uralensis. This study aims to evaluate the improvement of early ventricular remodeling and cardiac function in myocardial infarction (MI) rats by SNT. A MI model was established by ligation of the left anterior descending coronary artery. Following treatment for 4 weeks, ultrasonic echocardiography was performed. Myocardial histopathological changes were observed using haematoxylin and eosin staining. Collagens (type I and type III), transforming growth factor- β 1 (TGF- β 1), and Toll-like receptors (TLR-2 and TLR-4) were measured in plasma, serum, and myocardial tissue. SNT treatment decreased the infarct size, the left ventricular cavity area/heart cavity area ratio, and the left ventricle dimension at end systole and increased the left ventricular ejection fraction. SNT reduced the levels of TLR-2 and TLR-4 in myocardial tissue significantly and decreased the collagens content in serum and in myocardial tissue. SNT could partially reduce the level of TGF- β 1 in serum and in myocardial tissue. Our data suggest that the Chinese medicine formula SNT has the potential to improve early ventricular remodeling and cardiac function after MI.
    Evidence-based Complementary and Alternative Medicine 05/2014; 2014:141938. DOI:10.1155/2014/141938 · 1.88 Impact Factor
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    Merima Bublin · Heimo Breiteneder ·
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    ABSTRACT: Peanut seeds are currently widely used as source of human food ingredients in the United States of America and in European countries due to their high quality protein and oil content. This article describes the classification and molecular biology of peanut seed allergens with particular reference to their cross-reactivities. Currently, the IUIS allergen nomenclature subcommittee accepts 12 peanut allergens. Two allergens belong to the cupin and four to the prolamin superfamily, and six are distributed among profilins, Bet v 1-like proteins, oleosins, and defensins. Clinical observations frequently report an association of peanut allergy with allergies to legumes, tree nuts, seeds, fruits and pollen. Molecular cross-reactivity has been described between members of the Bet v 1-like proteins, the non-specific lipid transfer proteins, and the profilins. This review also addresses the less well-studied cross-reactivity between cupin and prolamin allergens of peanuts and of other plant food sources and the recently discovered cross-reactivity between peanut allergens of unrelated protein families.
    Current Allergy and Asthma Reports 04/2014; 14(4):426. DOI:10.1007/s11882-014-0426-8 · 2.77 Impact Factor

Publication Stats

10k Citations
1,375.12 Total Impact Points


  • 1998-2015
    • Medical University of Vienna
      • • Department of Pathophysiology and Allergy Research
      • • Division of General Dermatology
      • • Center for Pathophysiology, Infectiology and Immunology
      Wien, Vienna, Austria
  • 2004-2014
    • Vienna General Hospital
      Wien, Vienna, Austria
  • 1995-2014
    • IST Austria
      Klosterneuberg, Lower Austria, Austria
  • 1988-2009
    • University of Vienna
      • • Center for Pathophysiology, Infectology and Immunology
      • • Clinic for Internal Medicine I
      Wien, Vienna, Austria
  • 2006
    • RWTH Aachen University
      • Department of Dermatology
      Aachen, North Rhine-Westphalia, Germany
  • 2005
    • Universität Basel
      Bâle, Basel-City, Switzerland
  • 2002
    • Paul-Ehrlich-Institut
      Langen, Hesse, Germany
  • 2001-2002
    • University of Zurich
      Zürich, Zurich, Switzerland
    • Kore University of Enna
      Enna, Sicily, Italy
  • 1993-2002
    • University of Salzburg
      Salzburg, Salzburg, Austria
    • University of Florence
      Florens, Tuscany, Italy
  • 2000
    • Freie Universität Berlin
      Berlín, Berlin, Germany
  • 1999-2000
    • Humboldt-Universität zu Berlin
      Berlín, Berlin, Germany
  • 1997
    • Stanford University
      Palo Alto, California, United States