11. Immunological outcomes of allergen-specific immunotherapy in food allergyAnne-Marie Malby Schoos, Dominique Bullens, Bo Lund Chawes, Joana Costa, Liselot De Vlieger, Audrey DunnGalvin, Michelle M. Epstein, Johan Garssen, Christiane Hilger, Karen Knipping, Mihaela Zidarn, 2020, izvirni znanstveni članek Povzetek: IgE-mediated food allergies are caused by adverse immunologic responses to food proteins. Allergic reactions may present locally in different tissues such as skin, gastrointestinal and respiratory tract and may result is systemic life-threatening reactions. During the last decades, the prevalence of food allergies has significantly increased throughout the world, and considerable efforts have been made to develop curative therapies. Food allergen immunotherapy is a promising therapeutic approach for food allergies that is based on the administration of increasing doses of culprit food extracts, or purified, and sometime modified food allergens. Different routes of administration for food allergen immunotherapy including oral, sublingual, epicutaneous and subcutaneous regimens are being evaluated. Although a wealth of data from clinical food allergen immunotherapy trials has been obtained, a lack of consistency in assessed clinical and immunological outcome measures presents a major hurdle for evaluating these new treatments. Coordinated efforts are needed to establish standardized outcome measures to be applied in food allergy immunotherapy studies, allowing for better harmonization of data and setting the standards for the future research. Several immunological parameters have been measured in food allergen immunotherapy, including allergen-specific immunoglobulin levels, basophil activation, cytokines, and other soluble biomarkers, T cell and B cell responses and skin prick tests. In this review we discuss different immunological parameters and assess their applicability as potential outcome measures for food allergen immunotherapy that may be included in such a standardized set of outcome measures.
Ključne besede: food hypersensitivity, food intolerance, immunotherapy, immunology, food allergy, food allergens, oral immunotherapy
Objavljeno v DiRROS: 15.02.2021; Ogledov: 1257; Prenosov: 939
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12. Safety and efficacy of immunotherapy with the recombinant B-cell epitope-based grass pollen vaccine BM32Verena Niederberger, Angela Neubauer, Philippe Gevaert, Mihaela Zidarn, Margitta Worm, Werner Aberer, Hans Jørgen Malling, Oliver Pfaar, Ludger Klimek, Wolfgang Pfützner, 2018, izvirni znanstveni članek Povzetek: Background BM32 is a grass pollen allergy vaccine based on recombinant fusion proteins consisting of nonallergenic peptides from the IgE-binding sites of the 4 major grass pollen allergens and the hepatitis B preS protein. Objective We sought to study the safety and clinical efficacy of immunotherapy (allergen immunotherapy) with BM32 in patients with grass pollen-induced rhinitis and controlled asthma. Methods A double-blind, placebo-controlled, multicenter allergen immunotherapy field study was conducted for 2 grass pollen seasons. After a baseline season, subjects (n = 181) were randomized and received 3 preseasonal injections of either placebo (n = 58) or a low dose (80 [micro]g, n = 60) or high dose (160 [micro]g, n = 63) of BM32 in year 1, respectively, followed by a booster injection in autumn. In the second year, all actively treated subjects received 3 preseasonal injections of the BM32 low dose, and placebo-treated subjects continued with placebo. Clinical efficacy was assessed by using combined symptom medication scores, visual analog scales, Rhinoconjunctivitis Quality of Life Questionnaires, and asthma symptom scores. Adverse events were graded according to the European Academy of Allergy and Clinical Immunology. Allergen-specific antibodies were determined by using ELISA, ImmunoCAP, and ImmunoCAP ISAC. Results Although statistical significance regarding the primary end point was not reached, BM32-treated subjects, when compared with placebo-treated subjects, showed an improvement regarding symptom medication, visual analog scale, Rhinoconjunctivitis Quality of Life Questionnaire, and asthma symptom scores in both treatment years. This was accompanied by an induction of allergen-specific IgG without induction of allergen-specific IgE and a reduction in the seasonally induced increase in allergen-specific IgE levels in year 2. In the first year, more grade 2 reactions were observed in the active (n = 6) versus placebo (n = 1) groups, whereas there was almost no difference in the second year. Conclusions Injections of BM32 induced allergen-specific IgG, improved clinical symptoms of seasonal grass pollen allergy, and were well tolerated.
Ključne besede: allergy, allergen immunotherapy, B-cell epitope-based immunotherapy
Objavljeno v DiRROS: 17.12.2020; Ogledov: 1322; Prenosov: 856
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13. The culprit insect but not severity of allergic reactions to bee and wasp venom can be determined by molecular diagnosisPia Gattinger, Christian Lupinek, Lampros Kalogiros, Mira Šilar, Mihaela Zidarn, Peter Korošec, Christine Koessler, Natalija Novak, Rudolf Valenta, Irene Mittermann, 2018, izvirni znanstveni članek Povzetek: Background. Allergy to bee and wasp venom can lead to life-threatening systemic reactions. The identification of the culprit species is important for allergen-specific immunotherapy. Objectives. To determine a panel of recombinant bee and wasp allergens which is suitable for the identification of bee or wasp as culprit allergen sources and to search for molecular surrogates of clinical severity of sting reactions. Methods. Sera from eighty-seven patients with a detailed documentation of their severity of sting reaction (Mueller grade) and who had been subjected to titrated skin testing with bee and wasp venom were analyzed for bee and wasp-specific IgE levels by ImmunoCAPTM. IgE-reactivity testing was performed using a comprehensive panel of recombinant bee and wasp venom allergens (rApi m 1, 2, 3, 4, 5 and 10; rVes v 1 and 5) by ISAC chip technology, ImmunoCAP and ELISA. IgG4 antibodies to rApi m 1 and rVes v 5 were determined by ELISA and IgE/ IgG4 ratios were calculated. Results from skin testing, IgE serology and IgE/IgG4 ratios were compared with severity of sting reactions. Results. The panel of rApi m 1, rApi m 10, rVes v 1 and rVes v 5 allowed identification of the culprit venom in all but two of the 87 patients with good agreement to skin testing. Severities of sting reactions were not associated with results obtained by skin testing, venom-specific IgE levels or molecular diagnosis. Severe sting reactions were observed in patients showing < 1 ISU and < 2kUA/L of IgE to Api m 1 and/or Ves v 5. Conclusion. We identified a minimal panel of recombinant bee and wasp allergens for molecular diagnosis which may permit identification of bee and/or wasp as culprit insect in venom-sensitized subjects. The severity of sting reactions was not associated with parameters obtained by molecular diagnosis.
Ključne besede: allergy and immunology -- diagnosis, allergens -- diagnosis, hymenoptera, immunotherapy, bee, wasp, venom, sting reactions, molecular diagnosis, systemic reactions
Objavljeno v DiRROS: 23.11.2020; Ogledov: 12498; Prenosov: 1556
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15. Expression of FGFR1-4 in malignant pleural mesothelioma tissue and corresponding cell lines and its relationship to patient survival and FGFR inhibitor sensitivityGregor Vlačić, Mir Alireza Hoda, Thomas Klikovits, Katharina Sinn, Elisabeth Gschwandtner, Katja Mohorčič, Karin Schelch, Christine Pirker, Barbara Peter-Vörösmarty, Jelena Brankovic, Tanja Čufer, Aleš Rozman, Izidor Kern, 2019, izvirni znanstveni članek Povzetek: Malignant pleural mesothelioma (MPM) is a devastating malignancy with limited therapeutic options. Fibroblast growth factor receptors (FGFR) and their ligands were shown to contribute to MPM aggressiveness and it was suggested that subgroups of MPM patients could benefit from FGFR-targeted inhibitors. In the current investigation, we determined the expression of all four FGFRs (FGFR1-FGFR4) by immunohistochemistry in tissue samples from 94 MPM patients. From 13 of these patients, we were able to establish stable cell lines, which were subjected to FGFR1-4 staining, transcript analysis by quantitative RT-PCR, and treatment with the FGFR inhibitor infigratinib. While FGFR1 and FGFR2 were widely expressed in MPM tissue and cell lines, FGFR3 and FGFR4 showed more restricted expression. FGFR1 and FGFR2 showed no correlation with clinicopathologic data or patient survival, but presence of FGFR3 in 42% and of FGFR4 in 7% of patients correlated with shorter overall survival. Immunostaining in cell lines was more homogenous than in the corresponding tissue samples. Neither transcript nor protein expression of FGFR1-4 correlated with response to infigratinib treatment in MPM cell lines. We conclude that FGFR3 and FGFR4, but not FGFR1 or FGFR2, have prognostic significance in MPM and that FGFR expression is not suffcient to predict FGFR inhibitor response in MPM cell lines.
Ključne besede: malignant pleural mesothelioma, fibroblast growth factor receptors, azbestos, immunotherapy, chemotherapy, genomic analysis, infigratinib
Objavljeno v DiRROS: 07.10.2020; Ogledov: 12113; Prenosov: 1023
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16. Worldwide perspectives on venom allergyPeter Korošec, Thilo Jakob, Harfi Harb, Robert Heddle, Sarah Karabus, Ricardo de Lima Zollner, Julij Šelb, Bernard Yu-Hor Thong, Fares Zaitoun, David B. K. Golden, Michael Levin, 2019, pregledni znanstveni članek Povzetek: Venom immunotherapy is the standard of care for people with severe reactions and has been proven to reduce risk of future anaphylactic events. There is a moral imperative to ensure production, supply and worldwide availability of locally relevant, registered, standardized commercial venom extracts for diagnosis and treatment. Insects causing severe immediate allergic reactions vary by region worldwide. The most common culprits include honeybees (Apis mellifera), social wasps including yellow jackets (Vespula and Dolichovespula), paper wasps (Polistes) and hornets (Vespa), stinging ants (Solenopsis, Myrmecia, Pachycondyla, and Pogonomyrmex), and bumblebees (Bombus). Insects with importance in specific areas of the world include the Australian tick (Ixodes holocyclus), the kissing bug (Triatoma spp), horseflies (Tabanus spp), and mosquitoes (Aedes, Culex, Anopheles). Reliable access to high quality venom immunotherapy to locally relevant allergens is not available throughout the world. Many current commercially available therapeutic vaccines have deficiencies, are not suitable for, or are unavailable in vast areas of the globe. New products are required to replace products that are unstandardized or inadequate, particularly whole-body extract products. New products are required for insects in which no current treatment options exist. Venom immunotherapy should be promoted throughout the world and the provision thereof be supported by health authorities, regulatory authorities and all sectors of the health care service.
Ključne besede: allergy and immunology, venoms, Hymenoptera, bee venoms, wasp venoms, insecta, ants hornet, bumblebee, mosquitoes, venom immunotherapy, immunologic desensitization
Objavljeno v DiRROS: 23.09.2020; Ogledov: 1765; Prenosov: 1052
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