1. Hymenoptera venom immunotherapy in dogs : safety and clinical efficacyAna Rostaher, Nina Maria Fischer, Alessio Vigani, Barbara Šteblaj, Franco Martini, Salina Brem, Claude Favrot, Mitja Košnik, 2023, izvirni znanstveni članek Povzetek: Insect venom allergy is a potentially life-threatening allergic reaction following a bee, wasp, or ant sting. The only treatment to prevent further systemic sting reactions is venom immunotherapy (VIT), with an efficacy of up to 98% in humans. Prospective clinical data on VIT efficacy in dogs are currently lacking. In this investigation, 10 dogs with severe allergic reactions to either bee or wasp stings were treated with VIT. All dogs tolerated the therapy without adverse effects and the dogs which were re-stung tolerated the sting. This means that VIT is not only safe, but also efficacious in these patients. Furthermore, it was also shown that in addition to skin testing, two serum allergen-specific IgE tests were reliable to identify the underlying patients’ insect sensitization pattern. Ključne besede: anaphylaxis, angioedema, dogs, Hymenoptera allergy, urticaria, venom immunotherapy Objavljeno v DiRROS: 03.07.2025; Ogledov: 599; Prenosov: 333
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2. Risk factors for severe sting reactions and side effects during venom immunotherapyGunter Sturm, Eva Schadelbauer, Giorgia Marta, Patrizia Bonadonna, Mitja Košnik, 2025, pregledni znanstveni članek Povzetek: Understanding the risk factors leading to severe systemic sting reactions (SSRs) is crucial for initiating venom immunotherapy (VIT) and for educating affected individuals and their families. Some of these risk factors are well established, some are no longer considered risk factors, and some remain controversial. Well-established risk factors for severe SSRs include clonal mast cell disease, high baseline serum tryptase, and advanced age. The absence of skin symptoms and the rapid onset of symptoms are indicators of severe SSRs. Recent publications indicate that antihypertensive treatment and stings in the head and neck area are not risk factors for severe SSRs. VIT is the only available treatment that can potentially prevent further anaphylactic reactions. Although rare and generally manageable, individuals undergoing VIT may experience systemic adverse events (sAEs). More sAEs are expected in patients undergoing bee VIT compared with vespid VIT. The role of elevated baseline serum tryptase as a risk factor for sAEs remains debated, but if it is a factor, the risk is increased by only about 1.5-fold. Rapid updosing protocols, depending on the specific regimen, can also be associated with more sAEs. Severe initial SSRs, antihypertensive medication, high skin test reactivity, and high specific IgE levels are not risk factors for sAEs. Ključne besede: immunology, anaphylaxis, Hymenoptera venom allergy, risk factors, severe systemic sting reactions, side effects, venom immunotherapy Objavljeno v DiRROS: 02.07.2025; Ogledov: 511; Prenosov: 399
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4. Patients with detectable KIT p.D816V in peripheral blood are at high risk for adverse systemic events during venom immunotherapy and treatment failureAjda Demšar Luzar, Jakob Otorepec, Mitja Košnik, Peter Kopač, Julij Šelb, Peter Korošec, Matija Rijavec, 2024, izvirni znanstveni članek Ključne besede: immunology, allergy to poison Hymenoptera, peripheral leukocytes, venom immunotherapy Objavljeno v DiRROS: 19.02.2025; Ogledov: 777; Prenosov: 465
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5. Cellular and humoral response after induction of protection and after finishing Hymenoptera venom immunotherapyAjda Demšar Luzar, Matija Rijavec, Mitja Košnik, Urška Bidovec, Jerneja Debeljak, Mihaela Zidarn, Peter Kopač, Peter Korošec, 2024, izvirni znanstveni članek Ključne besede: Hymenoptera venom immunotherapy, sting challenge, biomarkers, serology, basophil activation test, follow-up Objavljeno v DiRROS: 19.02.2025; Ogledov: 743; Prenosov: 477
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6. Blood transcriptomics identifies multiple gene expression pathways associated with the clinical efficacy of Hymenoptera venom immunotherapyAjda Demšar Luzar, Peter Korošec, Mitja Košnik, Mihaela Zidarn, Matija Rijavec, 2024, izvirni znanstveni članek Povzetek: Allergen-specific venom immunotherapy (VIT) is a well-established therapy for Hymenoptera venom allergy (HVA). However, the precise mechanism underlying its clinical effect remains uncertain. Our study aimed to identify the molecular mechanisms associated with VIT efficiency. We prospectively included 19 patients with HVA undergoing VIT (sampled before the beginning of VIT, after reaching the maintenance dose, one year after finishing VIT, and after a sting challenge) and 9 healthy controls. RNA sequencing of whole blood was performed on an Illumina sequencing platform. Longitudinal transcriptomic profiling revealed the importance of the inhibition of the NFκB pathway and the downregulation of DUX4 transcripts for the early protection and induction of tolerance after finishing VIT. Furthermore, successful treatment was associated with inhibiting Th2, Th17, and macrophage alternative signalling pathways in synergy with the inhibition of the PPAR pathway and further silencing of the Th2 response. The immune system became activated when reaching the maintenance dose and was suppressed after finishing VIT. Finally, successful VIT restores the immune system’s balance to a state similar to that of healthy individuals. Our results underline the important role of the inhibition of four pathways in the clinical effect of VIT: Th2, Th17, NFκB, and macrophage signalling. Two biomarkers specific for successful VIT, regardless of the time of sampling, were C4BPA and RPS10-NUDT3 and should be further tested as potential biomarkers. Ključne besede: Hymenoptera venom immunotherapy, longitudinal transcriptomic profiling, tolerance induction, successful venom immunotherapy Objavljeno v DiRROS: 19.02.2025; Ogledov: 663; Prenosov: 412
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7. Epidemiology and risk factors of self-reported systemic allergic reactions to a Hymenoptera venom in beekeepers worldwide : a protocol for a systematic review of observational studiesTanja Carli, Igor Locatelli, Mitja Košnik, Andreja Kukec, 2022, pregledni znanstveni članek Povzetek: Introduction Systemic allergic reaction (SAR) to a Hymenoptera venom is a potentially life-threatening disorder. The rate of SAR between beekeepers in comparison with a healthy individual is different. The risk for an SAR is particularly high in beekeepers due to their persistent or seasonal exposure to the stinging Hymenoptera. We aim to provide a critical appraisal and a synthesis of evidence-based data from epidemiological observational studies, focusing on SARs to a Hymenoptera venom and the associated risk factors for SARs in beekeepers worldwide. Methods and analysis Searching will include seven electronic databases for published studies without language restrictions, from inception up to 3 August 2021, and it will be rerun for all electronic databases prior publication. Only epidemiological observational studies in beekeepers will be included. The risk of bias in the included studies will be appraised by using the Joanna Briggs Institute Critical Appraisal Checklist for Analytical Cross-Sectional Studies and the Newcastle-Ottawa Scale, adapted for cross-sectional studies. For the certainty of evidence, the Grading of Recommendations Assessment, Development and Evaluation approach will be used. Qualitative synthesis will be presented in a tabulated format with the selected characteristics across primary studies and the main outcome of interest. A meta-analysis is planned to be performed if there will be a sufficient number of homogeneous studies with complete data. The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols 2015 statement will guide the reporting of this systematic literature review. Ethics and dissemination No ethics approval is needed to conduct the systematic literature review since it will be solely based on the published literature. Findings will be disseminated through the relevant conferences, peer-review and open-access journals. Ključne besede: systemic allergic reaction (SAR), Hymenoptera venom, systematic literature review Objavljeno v DiRROS: 31.08.2022; Ogledov: 1756; Prenosov: 970
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8. Natural history of the hymenoptera venom sensitivity reactions in adults : study designSimona Perčič, Lidija Bojanić, Mitja Košnik, Andreja Kukec, 2022, izvirni znanstveni članek Povzetek: Background: Allergic reactions to Hymenoptera stings can have varying levels of severity,
according to the Müller grading system. Methods: By an epidemiological concept, this is a retrospective
cohort study. The observed cohort was represented by patients referred to the University Clinic
Golnik due to Hymenoptera allergic reaction in the period from 1997 to 2015. From the immunological
database of the University Clinic Golnik, we obtained laboratory data (sIgE, skin tests and basophil
activation test). The clinical characteristics of patients were obtained from BIRPIS. With the help of a
questionnaire, which was sent to each patient in the period from May 2019 to April 2021, we obtained
epidemiological data. For the assessment of the association between the severity of allergic reaction
for the observed outcome, the severity of the first allergic reaction after Hymenoptera sting was used.
Other variables were grouped according to risk factors. Discussion: We will identify the risk factors
that could play an important role in a severe systemic reaction: the aetiology of the Hymenoptera
sting, sex, age, history and severity of previous systemic reactions, being re-stung in an interval of
two months, the frequency of re-stings, atopy, genetic predisposition, preventive medication use,
other medication use, beekeeping or living next to beehives and why immunotherapy was not taken.
Laboratory data will also be analysed to determine if there is any association with laboratory tests and
the severity of the allergic reactions after Hymenoptera stings. Conclusions: Several new approaches
are introduced in the study design. The most important is that the protocol covers epidemiological
data gained from the questionnaire, as well as clinical data gained from the Immunological database
and BIRPIS database. We expect to obtain significant results that will explain the risk factors for the
natural history of Hymenoptera sting allergic reactions and will help allergologists, as well as general
doctors, when facing those patients allergic to Hymenoptera venom without immunotherapy. Ključne besede: hymenoptera venom allergy, risk factors, epidemiological association Objavljeno v DiRROS: 06.04.2022; Ogledov: 1969; Prenosov: 829
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9. Hymenoptera venom immunotherapy : immune mechanisms of induced protection and toleranceAjda Demšar Luzar, Peter Korošec, Mitja Košnik, Mihaela Zidarn, Matija Rijavec, 2021, pregledni znanstveni članek Povzetek: Hymenoptera venom allergy is one of the most severe allergic diseases, with a considerable prevalence of anaphylactic reaction, making it potentially lethal. In this review, we provide an overview of the current knowledge and recent findings in understanding induced immune mechanisms during different phases of venom immunotherapy. We focus on protection mechanisms that occur early, during the build-up phase, and on the immune tolerance, which occurs later, during and after Hymenoptera venom immunotherapy. The short-term protection seems to be established by the early desensitization of mast cells and basophils, which plays a crucial role in preventing anaphylaxis during the build-up phase of treatment. The early generation of blocking IgG antibodies seems to be one of the main reasons for the lower activation of effector cells. Long-term tolerance is reached after at least three years of venom immunotherapy. A decrease in basophil responsiveness correlates with tolerated sting challenge. Furthermore, the persistent decline in IgE levels and, by monitoring the cytokine profiles, a shift from a Th2 to Th1 immune response, can be observed. In addition, the generation of regulatory T and B cells has proven to be essential for inducing allergen tolerance. Most studies on the mechanisms and effectiveness data have been obtained during venom immunotherapy (VIT). Despite the high success rate of VIT, allergen tolerance may not persist for a prolonged time. There is not much known about immune mechanisms that assure longterm tolerance post-therapy. Ključne besede: allergy and immunology, hypersensitivity, immunotherapy, immune tolerance, venoms, Hymenoptera, Hymenoptera venom, short-term protection, long-term tolerance Objavljeno v DiRROS: 16.08.2021; Ogledov: 2911; Prenosov: 771
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10. 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: 14216; Prenosov: 2296
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