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  1. Article: T-cell subset changes during the first year of pre-seasonal allergoid allergen-specific immunotherapy.

    Reithofer, Manuel / Boell, Simone Lisa / Kitzmueller, Claudia / Horak, Fritz / Bohle, Barbara / Jahn-Schmid, Beatrice

    Heliyon

    2023  Volume 9, Issue 11, Page(s) e21878

    Abstract: Allergen-specific immunotherapy (AIT) is the only treatment for type I allergy, which achieves long-lasting effects. Repeated subcutaneous applications of allergen extracts cause a protective antibody response and an immune deviation of T cells. In AIT ... ...

    Abstract Allergen-specific immunotherapy (AIT) is the only treatment for type I allergy, which achieves long-lasting effects. Repeated subcutaneous applications of allergen extracts cause a protective antibody response and an immune deviation of T cells. In AIT with allergoids, chemically modified allergen extracts are injected. During a so-called special pre-seasonal application scheme, after the initial phase of applying increased doses of allergoids is followed by natural allergen exposure as a maintenance phase. The effectiveness of allergoid vaccines has been described regarding the improvement of clinical symptoms and the development of protective humoral responses. In this longitudinal observational study, we sought to investigate changes at the T cell level in pre-seasonal AIT with allergoid. Different subsets within CD4
    Language English
    Publishing date 2023-11-10
    Publishing country England
    Document type Journal Article
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2023.e21878
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  2. Article ; Online: Human neutrophils require short exposure to cytokines and allergen to become functional antigen-presenting cells.

    Polak, Dominika / Elbe-Bürger, Adelheid / Kitzmüller, Claudia / Zlabinger, Gerhard J / Bohle, Barbara

    Allergy

    2022  Volume 78, Issue 1, Page(s) 291–293

    MeSH term(s) Humans ; Cytokines ; Allergens ; Neutrophils ; Antigen-Presenting Cells ; Th2 Cells
    Chemical Substances Cytokines ; Allergens
    Language English
    Publishing date 2022-08-06
    Publishing country Denmark
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.15460
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: The role of IgG

    Strobl, Maria R / Demir, Hilal / Sánchez Acosta, Gabriela / Drescher, Anja / Kitzmüller, Claudia / Möbs, Christian / Pfützner, Wolfgang / Bohle, Barbara

    The Journal of allergy and clinical immunology

    2023  Volume 151, Issue 5, Page(s) 1371–1378.e5

    Abstract: Background: The induction of allergen-specific IgE-blocking antibodies is a hallmark of allergen immunotherapy (AIT). The inhibitory bioactivity has largely been attributed to IgG: Objectives: Here, the IgE-blocking activity and avidity of allergen- ... ...

    Abstract Background: The induction of allergen-specific IgE-blocking antibodies is a hallmark of allergen immunotherapy (AIT). The inhibitory bioactivity has largely been attributed to IgG
    Objectives: Here, the IgE-blocking activity and avidity of allergen-specific IgG
    Methods: Serum samples from 24 patients were collected before and regularly during AIT with birch pollen. Bet v 1-specific IgG
    Results: Bet v 1-specific IgG
    Conclusions: In spite of the constant avidity of AIT-induced allergen-specific IgG
    MeSH term(s) Humans ; Allergens ; Pollen ; Antibodies, Blocking ; Antigens, Plant ; Immunoglobulin E ; Desensitization, Immunologic ; Immunoglobulin G
    Chemical Substances Allergens ; Antibodies, Blocking ; Antigens, Plant ; Immunoglobulin E (37341-29-0) ; Immunoglobulin G
    Language English
    Publishing date 2023-01-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2023.01.005
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  4. Article ; Online: Sublingual immunotherapy with recombinant Mal d 1 downregulates the allergen-specific Th2 response.

    Kitzmüller, Claudia / Jahn-Schmid, Beatrice / Kinaciyan, Tamar / Bohle, Barbara

    Allergy

    2019  Volume 74, Issue 8, Page(s) 1579–1581

    MeSH term(s) Allergens/immunology ; Antigens, Plant/immunology ; Desensitization, Immunologic ; Epitopes, T-Lymphocyte/immunology ; Humans ; Plant Proteins/immunology ; Pollen/immunology ; Recombinant Proteins ; Rhinitis, Allergic, Seasonal/immunology ; Rhinitis, Allergic, Seasonal/metabolism ; Rhinitis, Allergic, Seasonal/therapy ; Sublingual Immunotherapy ; Th2 Cells/immunology ; Th2 Cells/metabolism
    Chemical Substances Allergens ; Antigens, Plant ; Epitopes, T-Lymphocyte ; MALD1 protein, Malus domestica ; Plant Proteins ; Recombinant Proteins
    Language English
    Publishing date 2019-04-10
    Publishing country Denmark
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.13779
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: IgE-blocking antibodies following SLIT with recombinant Mal d 1 accord with improved apple allergy.

    Sánchez Acosta, Gabriela / Kinaciyan, Tamar / Kitzmüller, Claudia / Möbs, Christian / Pfützner, Wolfgang / Bohle, Barbara

    The Journal of allergy and clinical immunology

    2020  Volume 146, Issue 4, Page(s) 894–900.e2

    Abstract: Background: We recently reported that 16 weeks of sublingual immunotherapy (SLIT) with recombinant (r) Mal d 1, but not rBet v 1, significantly improved birch pollen-related apple allergy. Allergen-specific IgE-blocking IgG antibodies have been ... ...

    Abstract Background: We recently reported that 16 weeks of sublingual immunotherapy (SLIT) with recombinant (r) Mal d 1, but not rBet v 1, significantly improved birch pollen-related apple allergy. Allergen-specific IgE-blocking IgG antibodies have been associated with clinical efficacy.
    Objective: We compared the quantity, quality, and IgE-blocking bioactivity of SLIT-induced Mal d 1-specific IgG antibodies in both treatment groups.
    Methods: Pre- and post-SLIT sera were assessed for rMal d 1-specific IgG antibodies in ELISA and for their ability to inhibit apple allergen-induced upregulation of CD63 on basophils from nontreated individuals with birch pollen-related apple allergy. Post-SLIT sera depleted of IgG1 or IgG4 were compared for their IgE-blocking activity. IgG1 binding to rMal d 1 was competed with rMal d 1 and rBet v 1 in ELISA.
    Results: SLIT with rMal d 1 and rBet v 1 induced comparable levels of rMal d 1-specific IgG1, IgG2, IgG3, and IgG4 antibodies. Only post-rMal d 1 SLIT sera displayed IgE-blocking activity, which was significantly reduced by depletion of IgG1 and less so by IgG4 depletion. In competition ELISA, IgG1 binding to Mal d 1 in post-rMal d 1 SLIT sera was fully inhibited with rMal d 1 but not with rBet v 1. Correspondingly, Bet v 1 was the more potent competitor for IgG1 binding to Mal d 1 in post-rBet v 1 SLIT sera.
    Conclusion: rMal d 1 SLIT for 16 weeks induced functional, primarily Mal d 1-specific IgE-blocking antibodies, whereas rBet v 1 SLIT induced Bet v 1-specific, Mal d 1-cross-reactive IgG antibodies with limited cross-blocking activity. These results provide a possible explanation for the limited effectiveness of birch pollen immunotherapy in birch pollen-related food allergy and indicate a dominant protective role of functional IgE-blocking IgG1 antibodies in the early phase of allergy treatment.
    MeSH term(s) Allergens/immunology ; Antibodies, Blocking/blood ; Antibodies, Blocking/immunology ; Antibody Specificity/immunology ; Antigens, Plant/immunology ; Basophils/immunology ; Basophils/metabolism ; Female ; Food Hypersensitivity/diagnosis ; Food Hypersensitivity/immunology ; Food Hypersensitivity/therapy ; Humans ; Immunoglobulin E/blood ; Immunoglobulin E/immunology ; Immunoglobulin G/immunology ; Male ; Malus/adverse effects ; Plant Proteins/immunology ; Protein Binding ; Recombinant Proteins ; Sublingual Immunotherapy ; Treatment Outcome
    Chemical Substances Allergens ; Antibodies, Blocking ; Antigens, Plant ; Immunoglobulin G ; MALD1 protein, Malus domestica ; Plant Proteins ; Recombinant Proteins ; Immunoglobulin E (37341-29-0)
    Language English
    Publishing date 2020-04-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 121011-7
    ISSN 1097-6825 ; 1085-8725 ; 0091-6749
    ISSN (online) 1097-6825 ; 1085-8725
    ISSN 0091-6749
    DOI 10.1016/j.jaci.2020.03.015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The secretome of irradiated peripheral blood mononuclear cells attenuates activation of mast cells and basophils.

    Laggner, Maria / Acosta, Gabriela Sánchez / Kitzmüller, Claudia / Copic, Dragan / Gruber, Florian / Altenburger, Lukas Matthäus / Vorstandlechner, Vera / Gugerell, Alfred / Direder, Martin / Klas, Katharina / Bormann, Daniel / Peterbauer, Anja / Shibuya, Akira / Bohle, Barbara / Ankersmit, Hendrik Jan / Mildner, Michael

    EBioMedicine

    2022  Volume 81, Page(s) 104093

    Abstract: Background: IgE-mediated hypersensitivity is becoming increasingly prevalent and activation of mast cells and basophils represent key events in the pathophysiology of allergy. We have previously reported that the secretome of γ-irradiated peripheral ... ...

    Abstract Background: IgE-mediated hypersensitivity is becoming increasingly prevalent and activation of mast cells and basophils represent key events in the pathophysiology of allergy. We have previously reported that the secretome of γ-irradiated peripheral blood mononuclear cells (PBMCsec) exerts beneficial anti-inflammatory effects. Yet, its ability to alleviate allergic symptoms has not been investigated so far.
    Methods: Several experimental in vitro and in vivo models have been used in this basic research study. A murine ear swelling model was used to study the effects of PBMCsec on 48/80-induced mast cell degranulation in vivo. The transcriptional profile of murine mast cells was analysed by single cell RNA sequencing (scRNAseq). Mast cell activation was studied in vitro using primary skin mast cells. Basophils from individuals allergic to birch pollens were used to investigate basophile activation by allergens. Transcriptomic and lipidomic analyses were used to identify mRNA expression and lipid species present in PBMCsec, respectively.
    Findings: Topical application of PBMCsec on mouse ears (C57BL/6) significantly reduced tissue swelling following intradermal injection of compound 48/80, an inducer of mast cell degranulation. Single cell RNA sequencing of PBMCsec-treated murine dermal mast cells (Balb/c) revealed a downregulation of genes involved in immune cell degranulation and Fc-receptor signalling. In addition, treatment of primary human dermal mast cells with PBMCsec strongly inhibited compound 48/80- and α-IgE-induced mediator release in vitro. Furthermore, PBMCsec remarkably attenuated allergen driven activation of basophils from allergic individuals. Transcriptomic analysis of these basophils showed that PBMCsec downregulated a distinct gene battery involved in immune cell degranulation and Fc-receptor signalling, corroborating results obtained from dermal mast cells. Finally, we identified the lipid fraction of PBMCsec as the major active ingredient involved in effector cell inhibition.
    Interpretation: Collectively, our data demonstrate that PBMCsec is able to reduce activation of mast cells and basophils, encouraging further studies on the potential use of PBMCsec for treating allergy.
    Funding: Austrian Research Promotion Agency (852748 and 862068, 2015-2019), Vienna Business Agency (2343727, 2018-2020), Aposcience AG, Austrian Federal Ministry of Education, Science and Research (SPA06/055), Danube Allergy Research Cluster, Austrian Science Fund (I4437 and P32953).
    MeSH term(s) Allergens ; Animals ; Basophils ; Humans ; Hypersensitivity ; Immunoglobulin E ; Leukocyte Count ; Leukocytes, Mononuclear/metabolism ; Lipids/pharmacology ; Mast Cells ; Mice ; Mice, Inbred C57BL ; Secretome
    Chemical Substances Allergens ; Lipids ; Immunoglobulin E (37341-29-0)
    Language English
    Publishing date 2022-06-04
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2022.104093
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  7. Article: Toll-like receptor ligands as adjuvants in allergy vaccines.

    Deifl, Stephan / Kitzmüller, Claudia / Bohle, Barbara

    Arbeiten aus dem Paul-Ehrlich-Institut (Bundesinstitut fur Impfstoffe und biomedizinische Arzneimittel) Langen/Hessen

    2013  Volume 97, Page(s) 159–163

    MeSH term(s) Adjuvants, Immunologic/administration & dosage ; Animals ; Humans ; Hypersensitivity/therapy ; Ligands ; Ovalbumin/immunology ; Recombinant Fusion Proteins/administration & dosage ; Toll-Like Receptors/agonists ; Vaccines/administration & dosage
    Chemical Substances Adjuvants, Immunologic ; Ligands ; Recombinant Fusion Proteins ; Toll-Like Receptors ; Vaccines ; Ovalbumin (9006-59-1)
    Language English
    Publishing date 2013
    Publishing country Germany
    Document type Journal Article
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Adjuvants and Vaccines Used in Allergen-Specific Immunotherapy Induce Neutrophil Extracellular Traps.

    Karacs, Jasmine / Reithofer, Manuel / Kitzmüller, Claudia / Kraller, Markus / Schmalz, Stefanie / Bleichert, Sonja / Huppa, Johannes B / Stockinger, Hannes / Bohle, Barbara / Jahn-Schmid, Beatrice

    Vaccines

    2021  Volume 9, Issue 4

    Abstract: Aluminum hydroxide (alum) and monophosphoryl-lipid A (MPLA) are conventional adjuvants in vaccines for allergen-specific immunotherapy (AIT). Alum triggers the release of neutrophil extracellular traps (NETs) by neutrophils. NETs contain expelled ... ...

    Abstract Aluminum hydroxide (alum) and monophosphoryl-lipid A (MPLA) are conventional adjuvants in vaccines for allergen-specific immunotherapy (AIT). Alum triggers the release of neutrophil extracellular traps (NETs) by neutrophils. NETs contain expelled decondensed chromatin associated with granular material and may act as danger-associated molecular patterns and activate antigen-presenting cells. We investigated whether adjuvant-induced NETs contribute to innate responses to AIT-vaccines. Human neutrophils were incubated with alum, MPLA and adjuvant-containing AIT-vaccine preparations. NETs were verified by time-lapse and confocal fluorescence microscopy and quantitatively assessed by DNA and elastase release and ROS production. In contrast to MPLA, alum represented a potent trigger for NET release. Vaccine formulations containing alum resulted in less NET release than alum alone, whereas the vaccine containing MPLA induced stronger NET responses than MPLA alone. NETs and alum alone and synergistically increased the expression of molecules involved in antigen presentation, i.e., CD80, CD86 and CD83, by peripheral blood monocytes. Monocyte priming with NETs resulted in individually differing IL-1β- and IL-6-responses. Thus, NETs induced by adjuvants in AIT-vaccines can provide autonomous and cooperative effects on early innate responses. The high diversity of individual innate responses to adjuvants and AIT-vaccines may affect their therapeutic efficacy.
    Language English
    Publishing date 2021-04-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines9040321
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  9. Article ; Online: T-cell-derived cytokines enhance the antigen-presenting capacity of human neutrophils.

    Samadi, Nazanin / Polak, Dominika / Kitzmüller, Claudia / Steinberger, Peter / Zlabinger, Gerhard J / Jahn-Schmid, Beatrice / Bohle, Barbara

    European journal of immunology

    2019  Volume 49, Issue 9, Page(s) 1441–1443

    Abstract: Activated allergen-specific Th2 and Th1 cells release cytokines that transform neutrophils into functional APCs characterized by the expression of HLA-DR and CD58 as well as enhanced survival and antigen uptake, irrespectively of the presence of IL-10, ... ...

    Abstract Activated allergen-specific Th2 and Th1 cells release cytokines that transform neutrophils into functional APCs characterized by the expression of HLA-DR and CD58 as well as enhanced survival and antigen uptake, irrespectively of the presence of IL-10, which reduces allergen uptake by neutrophils.
    MeSH term(s) Allergens/immunology ; Antigen Presentation/immunology ; CD4-Positive T-Lymphocytes/immunology ; CD58 Antigens/immunology ; Cytokines/immunology ; HLA-DR Antigens/immunology ; Humans ; Lymphocyte Activation/immunology ; Neutrophils/immunology ; Th1 Cells/immunology ; Th2 Cells/immunology
    Chemical Substances Allergens ; CD58 Antigens ; Cytokines ; HLA-DR Antigens
    Language English
    Publishing date 2019-08-06
    Publishing country Germany
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 120108-6
    ISSN 1521-4141 ; 0014-2980
    ISSN (online) 1521-4141
    ISSN 0014-2980
    DOI 10.1002/eji.201848057
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  10. Article ; Online: IgE-cross-blocking antibodies to Fagales following sublingual immunotherapy with recombinant Bet v 1.

    Grilo, João Rodrigues / Kitzmüller, Claudia / Aglas, Lorenz / Sánchez Acosta, Gabriela / Vollmann, Ute / Ebner, Christof / Horak, Fritz / Kinaciyan, Tamar / Radauer, Christian / Ferreira, Fatima / Jahn-Schmid, Beatrice / Bohle, Barbara

    Allergy

    2021  Volume 76, Issue 8, Page(s) 2555–2564

    Abstract: Background: Evidence has accumulated that birch pollen immunotherapy reduces rhinoconjunctivitis to pollen of birch homologous trees. Therapeutic efficacy has been associated with IgE-blocking IgG antibodies. We have recently shown that sera collected ... ...

    Abstract Background: Evidence has accumulated that birch pollen immunotherapy reduces rhinoconjunctivitis to pollen of birch homologous trees. Therapeutic efficacy has been associated with IgE-blocking IgG antibodies. We have recently shown that sera collected after 16 weeks of sublingual immunotherapy with recombinant Bet v 1 (rBet v 1-SLIT) display strong IgE-blocking bioactivity for Bet v 1. Here, we assessed whether rBet v 1-SLIT-induced IgG antibodies display cross-blocking activity to related allergens in Fagales pollen.
    Methods: IgE, IgG1 and IgG4 reactivity to recombinant Bet v 1, Aln g 1, Car b 1, Ost c 1, Cor a 1, Fag s 1, Cas s 1 and Que a 1 were assessed in pre- and post-SLIT samples of 17 individuals by ELISA. A basophil inhibition assay using stripped basophils re-sensitized with a serum pool containing high Bet v 1-specific IgE levels was established and used to assess CD63 expression in response to allergens after incubation with pre-SLIT or post-SLIT samples. IgG1 and IgG4 were depleted from post-SLIT samples to assess its contribution to IgE-cross-blocking.
    Results: Sublingual immunotherapy with recombinant Bet v 1 boosted cross-reactive IgE antibodies and induced IgG1 and IgG4 antibodies with inter- and intra-individually differing reactivity to the homologs. Highly variable cross-blocking activities of post-SLIT samples to the different allergens were found. IgG1 and IgG4 antibodies displayed cross-blocking activity with individual variance.
    Conclusions: Our mechanistic approach suggested that immunotherapy with the reference allergen Bet v 1 induces individual repertoires of cross-reactive IgG1 and IgG4 antibodies. The cross-blocking bioactivity of these antibodies was also highly variable and neither predictable from protein homology nor IgE-cross-reactivity.
    MeSH term(s) Allergens ; Antibodies, Blocking ; Antigens, Plant/immunology ; Antigens, Plant/therapeutic use ; Fagales ; Humans ; Immunoglobulin E ; Plant Proteins ; Recombinant Proteins ; Sublingual Immunotherapy
    Chemical Substances Allergens ; Antibodies, Blocking ; Antigens, Plant ; Plant Proteins ; Recombinant Proteins ; Bet v 1 allergen, Betula (126161-14-6) ; Immunoglobulin E (37341-29-0)
    Language English
    Publishing date 2021-05-06
    Publishing country Denmark
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.14817
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