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1.
Hereditary α-tryptasemia is associated with anaphylaxis to antibiotics and monoclonal antibodies
Peter Korošec, Jonathan J. Lyons, Manca Svetina, Monika Koudová, Martina Bittóová, Mihaela Zidarn, Lenka Sedláčková, Matija Rijavec, Peter Kopač, 2025, izvirni znanstveni članek

Povzetek: Background Hereditary α-tryptasemia, a genetic trait caused by increased α-tryptase copy number, is associated with idiopathic and venom anaphylaxis. Objective We aimed to determine the impact of tryptase genotypes on drug-induced anaphylaxis. Methods A prospective discovery cohort of 99 patients from a referral center in Slovenia with acute anaphylaxis to drugs underwent tryptase genotyping by droplet digital PCR. For validation, we included a cohort of 26 patients from the Czech Republic. Associated inciting agents and the severity of the reactions were subsequently examined. Results Hereditary α-tryptasemia was associated with drug-induced anaphylaxis with a prevalence of 13% (n = 13 of 99) in the discovery cohort and 15% in the validation cohort (n = 4 of 26). Hereditary α-tryptasemia was identified in every individual with elevated basal serum tryptase levels (11.6-21.9 ng/mL; n = 14) within both cohorts of patients. Hereditary α-tryptasemia was more prevalent in individuals with antibiotic- or mAb-induced anaphylaxis in both the discovery and validation cohorts (n = 13 of 51; 26%) compared to those with anaphylaxis resulting from neuromuscular blocking agents, nonsteroidal anti-inflammatory drugs, contrast, chlorhexidine, or other drugs (n = 5 of 74; 7%; P = .02; odds ratio = 4.1; 95% CI, 1.3-11.1). Overall, we found fewer individuals with no ⍺-tryptase than in the general population, and there was a trend for subjects with more ⍺-tryptase copies to have more severe reactions. Thus, among subjects with three ⍺-tryptase copies, the prevalence of severe anaphylaxis was 73%, compared with 59% with one to two ⍺-tryptase copies and 58% for subjects without ⍺-tryptase. Conclusions Risk for anaphylaxis to antibiotics and biologics is associated with inherited differences in α-tryptase–encoding copies at Tryptase α/β1 .
Ključne besede: immunology, drug allergy, anaphylaxis, antibiotics, monoclonal antibodies, α-tryptase, hereditary α-tryptasemia
Objavljeno v DiRROS: 18.06.2025; Ogledov: 144; Prenosov: 76
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2.
Exploring beekeepers’ experiences and perceptions of anaphylaxis risks : a qualitative study to inform targeted health education programs
Tea Močnik, Sabina Ličen, Mihaela Zidarn, Mirko Prosen, 2024, izvirni znanstveni članek

Povzetek: Background: Beekeeping plays crucial natural and economic roles but also poses health risks, as bee stings can cause severe allergic reactions like anaphylaxis, a potentially life-threatening condition that requires timely intervention. Understanding symptoms and the proper use of adrenaline autoinjectors is essential to minimize risks. This study aimed to assess the need for education on anaphylaxis and to develop a health education program to enhance beekeepers’ preparedness and safety. Methods: A qualitative descriptive interpretative method was employed. Two focus groups were conducted, one with eight health care professionals specializing in allergy and clinical immunology and the other with six active beekeepers. The data were analyzed via content analysis using QDA Miner® Lite v3.0.5 software. Results: The analysis structure comprises five thematic areas: (1) the management of anaphylaxis; (2) the prevention of anaphylaxis; (3) health education approaches; (4) systemic approaches in prevention; and (5) adrenaline autoinjectors. The results highlight key challenges, including the need for better strategies to manage anaphylaxis, improve prevention, and provide practical educational programs for beekeepers. There is also a need for better collaboration between health care professionals and beekeepers, as well as improved access to and knowledge of adrenaline autoinjectors. Conclusions: Targeted education for beekeepers on recognizing anaphylaxis symptoms and using adrenaline autoinjectors is essential for timely intervention and preventing severe outcomes. Given their exposure to bee stings, beekeepers require proper training and regular practice to improve preparedness and safety. This research underscores the need for a comprehensive educational program to reduce anaphylaxis risk and enhance safety in beekeeping.
Ključne besede: beekeepers, hypersensitivity reaction, epinephrine, exposure, awareness, prevention, health education
Objavljeno v DiRROS: 16.05.2025; Ogledov: 260; Prenosov: 154
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3.
Autoimmune mast cell activation test as a diagnostic tool in chronic spontaneous urticaria
Ana Koren, Luka Dejanović, Matija Rijavec, Peter Kopač, Mojca Bizjak, Mihaela Zidarn, Mitja Košnik, Peter Korošec, 2024, izvirni znanstveni članek

Povzetek: first_pagesettingsOrder Article Reprints Open AccessArticle Autoimmune Mast Cell Activation Test as a Diagnostic Tool in Chronic Spontaneous Urticaria by Ana Koren 1,*ORCID,Luka Dejanović 1ORCID,Matija Rijavec 1,2ORCID,Peter Kopač 1,3ORCID,Mojca Bizjak 1ORCID,Mihaela Zidarn 1,3,Mitja Košnik 1,3ORCID andPeter Korošec 1,4 1 University Clinic of Respiratory and Allergic Diseases Golnik, 4204 Golnik, Slovenia 2 Biotechnical Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia 3 Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia 4 Faculty of Pharmacy, University of Ljubljana, 1000 Ljubljana, Slovenia * Author to whom correspondence should be addressed. Int. J. Mol. Sci. 2024, 25(17), 9281; https://doi.org/10.3390/ijms25179281 Submission received: 25 July 2024 / Revised: 23 August 2024 / Accepted: 25 August 2024 / Published: 27 August 2024 (This article belongs to the Special Issue Progression of Allergy and Immune Response) Downloadkeyboard_arrow_down Browse Figures Review Reports Versions Notes Abstract Chronic spontaneous urticaria (CSU) is associated with skin mast cell activation, and its triggering mechanisms are not completely elucidated. Evidence suggests an autoimmune component of CSU. Our aim was to assess the usefulness of an autoimmune mast cell activation test (aiMAT) for diagnosing and differentiating CSU into different subtypes. We enrolled 43 patients with active, uncontrolled CSU before starting treatment with omalizumab and 15 controls. Patients were evaluated based on omalizumab response. aiMATs were performed using non-IgE-sensitized (NS) or myeloma IgE-sensitized (S) LAD2 cells, which were then stimulated with CSU/control sera (25 µL and 10 µL). The expression of CD63 was assessed with flow cytometry. CD63 response on NS-LAD2 was significantly increased in CSU patients compared to controls after the stimulation with 25 µL CSU/control sera (p = 0.0007) and with 10 µL CSU/control sera (p = 0.0001). The ROC curve analysis demonstrated an area under the curve (AUC) of 0.82. The cutoff for autoimmune-non-IgE-sensitized-MAT was 40.3% CD63+ LAD2, which resulted in 73.3% sensitivity and 81.4% specificity. CD63 response on S-LAD2 was significantly increased in CSU patients compared to controls after the stimulation with 25 µL CSU/control sera (p = 0.03). The ROC curve analysis demonstrated an AUC of 0.66. The cutoff for the autoimmune-myeloma IgE-sensitized-MAT was 58.4% CD63+ cells, which resulted in 62.8% sensitivity and 66.7% specificity. Overall, 36 out of 43 (84%) patients responded to omalizumab, and 7 (16%) were nonresponders. We found no differences between LAD2 CD63 response and response to omalizumab. In conclusion, aiMAT could represent a new diagnostic tool in CSU. Additional studies are needed to evaluate the potential benefits during omalizumab therapy.
Ključne besede: mast cell activation test, LAD2, chronic spontaneous urticaria, omalizumab, CD63 expression
Objavljeno v DiRROS: 06.03.2025; Ogledov: 262; Prenosov: 153
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Blood transcriptomics identifies multiple gene expression pathways associated with the clinical efficacy of Hymenoptera venom immunotherapy
Ajda 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: 331; Prenosov: 186
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6.
High burden of clonal mast cell disorders and hereditary ▫$α-tryptasemia$▫ in patients who need Hymenoptera venom immunotherapy
Peter Korošec, Gunter Sturm, Jonathan J. Lyons, Tinkara Pirc Marolt, Manca Svetina, Mitja Košnik, Mihaela Zidarn, Mark Kačar, Nina Frelih, Nika Lalek, Ajda Demšar Luzar, Samo Zver, Matevž Škerget, Ewa Czarnobilska, Wojciech Dyga, Sanja Popović-Grle, Miroslav Samaržija, Lisa Arzt-Gradwohl, Urban Čerpes, Grzegorz Porebski, Branko Pevec, Eva Schadelbauer, Peter Kopač, Julij Šelb, Matija Rijavec, 2024, izvirni znanstveni članek

Povzetek: Background In patients who require venom immunotherapy (VIT), there is a need to identify underlying mast cell (MC) disorders since these may affect the risk and severity of future sting reactions and the long-term effectiveness of VIT. Methods 1319 individuals with Hymenoptera venom allergy (HVA) who needed VIT from referral centers in Slovenia, Austria, Croatia, and Poland underwent examination for KIT p.D816V in peripheral blood leukocytes (PBL) using a highly sensitive PCR test and tryptase genotyping by digital droplet PCR. We also included 183 control individuals with large local reactions (LLRs) to Hymenoptera stings and with asymptomatic sensitization to Hymenoptera venoms. Results 285 of 1319 individuals recommended for VIT (21.6%) were positive for KIT p.D816V in PBL, preferably those who present with severe reaction (33.9% [n = 207 of 610] with Ring-Messmer grade 3–4 vs. 11% [n = 78 of 709] with Grade 1–2; p < .0001), whereas only 1.3% (n = 2 of 152) of controls with LLR and none with asymptomatic sensitization (n = 31) had KIT p.D816V. KIT p.D816V allelic burden was higher in those with severe reaction (median 0.018% [n = 207] in Grade 3–4 vs. 0.001% [n = 78] in Grade 1–2; p < .0001), and the majority had normal baseline serum tryptase levels (69% [n = 196 of 285]). All KIT p.D816V-positive individuals (n = 41) who underwent bone marrow (BM) biopsy were found to have underlying clonal diseases, principally BM mastocytosis. HαT was also associated with severe HVA and symptoms (p < .01), and remarkably, 31.0% (n = 31 of 100) were found to have concomitant KIT p.D816V. Concomitant HαT and KIT p.D816V showed an additive effect, and having both was associated with the highest risk for severe HVA, even higher than having either HαT or KIT p.D816V alone (OR = 3.8; p < .01). Conclusions By employing prospective universal tryptase genotyping and examination for KIT p.D816V in PBL in large HVA populations, we have demonstrated a high burden of clonal MC disorders and HαT in patients who require VIT.
Ključne besede: anaphylaxis, hereditary α-tryptasemia, hypersensitivity, immunotherapy, mast cell, mastocytosis, venom
Objavljeno v DiRROS: 17.06.2024; Ogledov: 910; Prenosov: 486
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7.
Patch testing with the European baseline series and 10 added allergens : single centre study of 748 patients
Mojca Bizjak, Katja Adamič, Nisera Bajrović, Renato Eržen, Maja Jošt, Peter Kopač, Mitja Košnik, Nika Lalek, Mihaela Zidarn, Dejan Dinevski, 2022, izvirni znanstveni članek

Povzetek: Background. The European baseline series (EBS) of contact allergens is subject to change. An allergen is considered for inclusion when routine patch testing of patients with suspected contact dermatitis results in ≥ 0.5% prevalence rate. Objectives. We aimed to determine the frequency of sensitizations to 30 EBS allergens and 10 locally added allergens. Additionally, we assessed the strength and evolution of reactions to all tested allergens and co-reactivity of additional allergens. Methods. Patch testing with our baseline series of 40 allergens was done in 748 consecutive adults. Tests were applied to the upper back and removed by patients after 48 hours. Readings were done on day 3 (D3) and D6 or D7 (D6/7). Positive reactions fulfilled the criteria of at least one plus (+) reaction. Retrospective analysis was done. Results. Eight allergens not listed in the EBS had ≥ 0.5% prevalence rate (i.e., cocamidopropyl betaine, thiomersal, disperse blue mix 106/124, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea, propylene glycol, Compositae mix II, and dexamethasone-21-phosphate), and 16.6% of positive reactions would have been missed without D6/7 readings. Conclusion. We propose further studies to evaluate whether cocamidopropyl betaine, disperse blue mix 106/124, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea, and Compositae mix II need to be added to the EBS.
Ključne besede: allergy and immunology -- diagnosis, hypersensitivity -- diagnosis, skin tests, clinical epidemiology, baseline series, contact sensitization, patch tests, simultaneous reactivity
Objavljeno v DiRROS: 24.06.2022; Ogledov: 1275; Prenosov: 462
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8.
Behavioural patterns in allergic rhinitis medication in Europe : a study using 28 MASK-air® real-world data
Bernardo Sousa-Pinto, Ana Sá-Sousa, Rafael José Vieira, Rita Amaral, Ludger Klimek, Wienczyslawa Czarlewski, Josep M. Antò i Boquè, Oliver Pfaar, Anna Bedbrook, Mihaela Zidarn, Joao A. Fonseca, Jean Bousquet, 2022, izvirni znanstveni članek

Povzetek: Background. Co-medication is common among patients with allergic rhinitis (AR), but its dimension and patterns are unknown. This is particularly relevant since AR is understood differently across European countries, as reflected by rhinitis-related search patterns in Google Trends. This study aims to assess AR co-medication and its regional patterns in Europe, using real-world data. Methods. We analysed 2015-2020 MASK-air® European data. We compared days under no medication, monotherapy, and co-medication using the visual analogue scale (VAS) levels for overall allergic symptoms (“VAS Global Symptoms”) and impact of AR on work. We assessed the monthly use of different medication schemes, performing separate analyses by region (defined geographically or by Google Trends patterns). We estimated the average number of different drugs reported per patient within one year. Results. We analysed 222,024 days (13,122 users), including 63,887 days (28.8%) under monotherapy, and 38,315 (17.3%) under co-medication. The median “VAS Global Symptoms” was 7 for no medication days, 14 for monotherapy and 21 for co-medication (p<0.001). Medication use peaked during the spring, with similar patterns across different European regions (defined geographically or by Google Trends). Oral H1-antihistamines were the most common medication in single and co-medication. Each patient reported using an annual average of 2.7 drugs, with 80% reporting two or more. Conclusions. AR medication patterns are similar across European regions. One third of treatment days involved co-medication. These findings suggest that patients treat themselves according to their symptoms (irrespective of how they understand AR), and that co-medication use is driven by symptom severity.
Ključne besede: asthma -- drug therapy, rhinitis -- drug therapy, allergic rhinitis -- drug therapy, visual analogue scale, histamine antagonists, antihistamines, behavioural patterns, medication patterns, real-world data
Objavljeno v DiRROS: 14.03.2022; Ogledov: 1626; Prenosov: 515
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9.
Allergies and COVID-19 vaccines : an ENDA/EAACI position paper
Annick Barbaud, Lene Heise Garvey, Alessandra Arcolaci, Knut Brockow, Francesca Mori, Cristobalina Mayorga, Maja Jošt, Mitja Košnik, Mihaela Zidarn, Maria J Torres, 2022, izvirni znanstveni članek

Povzetek: Anaphylaxis, which is rare, has been reported after COVID 19 vaccination, but its management is not standardized. Method. Members of the European Network for Drug Allergy and the European Academy of Allergy and Clinical Immunology interested in drug allergy participated in an online questionnaire on pre-vaccination screening and management of allergic reactions to COVID-19 vaccines, and literature was analysed. Results. No death due to anaphylaxis to COVID-19 vaccines has been confirmed in scientific literature. Potential allergens, polyethylene glycol (PEG), polysorbate and tromethamine, are excipients. The authors propose allergy evaluation of persons with the following histories: 1- anaphylaxis to injectable drug or vaccine containing PEG or derivatives; 2- anaphylaxis to oral/topical PEG containing products; 3-recurrent anaphylaxis of unknown cause; 4-suspected or confirmed allergy to any mRNA vaccine, 5-confirmed allergy to PEG or derivatives. We recommend a prick-to-prick skin test with the left over solution in the suspected vaccine vial to avoid waste. Prick test panel should include PEG 4000 or 3500, PEG 2000 and polysorbate 80. The value of in vitro test is arguable. Conclusions. These recommendations will lead to a better knowledge of the management and mechanisms involved in anaphylaxis to COVID-19 vaccines and enable more people with history of allergy to be vaccinated.
Ključne besede: SARS-CoV-2, COVID-19, COVID-19 vaccines, allergens, anapylaxis, drug hypersensitivity
Objavljeno v DiRROS: 07.02.2022; Ogledov: 1861; Prenosov: 499
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10.
Robust saliva-based RNA extraction-free one-step nucleic acid amplification test for mass SARS-CoV-2 monitoring
Eva Rajh, Tina Šket, Arne Praznik, Petra Sušjan, Alenka Šmid, Dunja Urbančič, Irena Mlinarič-Raščan, Polona Kogovšek, Tina Demšar, Mojca Milavec, Katarina Prosenc, Žiga Jensterle, Mihaela Zidarn, Viktorija Tomič, Gabriele Turel, Tatjana Lejko-Zupanc, Roman Jerala, Mojca Benčina, 2021, izvirni znanstveni članek

Povzetek: Early diagnosis with rapid detection of the virus plays a key role in preventing the spread of infection and in treating patients effectively. In order to address the need for a straightforward detection of SARS-CoV-2 infection and assessment of viral spread, we developed rapid, sensitive, extraction-free one-step reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and reverse transcription loop-mediated isothermal amplification (RT-LAMP) tests for detecting SARS-CoV-2 in saliva. We analyzed over 700 matched pairs of saliva and nasopharyngeal swab (NSB) specimens from asymptomatic and symptomatic individuals. Saliva, as either an oral cavity swab or passive drool, was collected in an RNA stabilization buffer. The stabilized saliva specimens were heat-treated and directly analyzed without RNA extraction. The diagnostic sensitivity of saliva-based RT-qPCR was at least 95% in individuals with subclinical infection and outperformed RT-LAMP, which had at least 70% sensitivity when compared to NSBs analyzed with a clinical RT-qPCR test. The diagnostic sensitivity for passive drool saliva was higher than that of oral cavity swab specimens (95% and 87%, respectively). A rapid, sensitive one-step extraction-free RT-qPCR test for detecting SARS-CoV-2 in passive drool saliva is operationally simple and can be easily implemented using existing testing sites, thus allowing high-throughput, rapid, and repeated testing of large populations. Furthermore, saliva testing is adequate to detect individuals in an asymptomatic screening program and can help improve voluntary screening compliance for those individuals averse to various forms of nasal collections.
Ključne besede: SARS-CoV-2, COVID-19, COVID-19 serological testing, real-time polymerase chain reaction, saliva, oral cavity swab, passive drool, pooling
Objavljeno v DiRROS: 09.11.2021; Ogledov: 1900; Prenosov: 807
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