1. High burden of clonal mast cell disorders and hereditary ▫$α-tryptasemia$▫ in patients who need Hymenoptera venom immunotherapyPeter 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, original scientific article Abstract: 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. Keywords: anaphylaxis, hereditary α-tryptasemia, hypersensitivity, immunotherapy, mast cell, mastocytosis, venom Published in DiRROS: 17.06.2024; Views: 383; Downloads: 248 Full text (7,30 MB) This document has many files! More... |
2. Patch testing with the European baseline series and 10 added allergens : single centre study of 748 patientsMojca Bizjak, Katja Adamič, Nisera Bajrović, Renato Eržen, Maja Jošt, Peter Kopač, Mitja Košnik, Nika Lalek, Mihaela Zidarn, Dejan Dinevski, 2022, original scientific article Abstract: 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. Keywords: allergy and immunology -- diagnosis, hypersensitivity -- diagnosis, skin tests, clinical epidemiology, baseline series, contact sensitization, patch tests, simultaneous reactivity Published in DiRROS: 24.06.2022; Views: 904; Downloads: 313 Link to file |
3. Behavioural patterns in allergic rhinitis medication in Europe : a study using 28 MASK-air® real-world dataBernardo 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, original scientific article Abstract: 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. Keywords: asthma -- drug therapy, rhinitis -- drug therapy, allergic rhinitis -- drug therapy, visual analogue scale, histamine antagonists, antihistamines, behavioural patterns, medication patterns, real-world data Published in DiRROS: 14.03.2022; Views: 1008; Downloads: 334 Link to file |
4. Allergies and COVID-19 vaccines : an ENDA/EAACI position paperAnnick Barbaud, Lene Heise Garvey, Alessandra Arcolaci, Knut Brockow, Francesca Mori, Cristobalina Mayorga, Maja Jošt, Mitja Košnik, Mihaela Zidarn, Maria J Torres, 2022, original scientific article Abstract: 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. Keywords: SARS-CoV-2, COVID-19, COVID-19 vaccines, allergens, anapylaxis, drug hypersensitivity Published in DiRROS: 07.02.2022; Views: 1182; Downloads: 347 Link to file |
5. Robust saliva-based RNA extraction-free one-step nucleic acid amplification test for mass SARS-CoV-2 monitoringEva 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, original scientific article Abstract: 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. Keywords: SARS-CoV-2, COVID-19, COVID-19 serological testing, real-time polymerase chain reaction, saliva, oral cavity swab, passive drool, pooling Published in DiRROS: 09.11.2021; Views: 1435; Downloads: 635 Link to full text |
6. Hymenoptera venom immunotherapy : immune mechanisms of induced protection and toleranceAjda Demšar Luzar, Peter Korošec, Mitja Košnik, Mihaela Zidarn, Matija Rijavec, 2021, review article Abstract: 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. Keywords: allergy and immunology, hypersensitivity, immunotherapy, immune tolerance, venoms, Hymenoptera, Hymenoptera venom, short-term protection, long-term tolerance Published in DiRROS: 16.08.2021; Views: 1351; Downloads: 430 Link to file |
7. Usefulness of rapid antigen testing for SARS-CoV-2 screening of healthcare workers : ǂa ǂpilot studyAnja Šterbenc, Viktorija Tomič, Urška Bidovec, Katja Vrankar, Aleš Rozman, Mihaela Zidarn, 2021, other scientific articles Abstract: Background. Identification of infected healthcare workers (HCWs) is an important step in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) transmission control. Rapid antigen tests (RATs) are considered an important addition to molecular tests in diagnosing coronavirus disease 2019 (COVID-19), mainly because of their fast turnaround time, easier analytical procedure and lower price. However, real-life studies on the usefulness of such testing for screening of HCWs are limited. Methods. Physicians, nurses and hospital attendants currently working at the University Clinic of Respiratory and Allergic Diseases Golnik were invited to participate in the pilot study. Nasopharyngeal swabs were obtained three times per week for two consecutive weeks and tested with a point-of-care RAT and reverse transcription polymerase chain reaction (RT-PCR). Serum samples were obtained at the beginning of the study and 2 weeks after the last swab was collected to evaluate the serological status. Results. A total of 191 nasopharyngeal swabs from 36 HCWs were obtained. None of the samples tested was positive for the presence of SARS-CoV-2 antigen, whereas two HCWs tested positive on RT-PCR. Of these, one HCW had a newly identified SARS-CoV-2 infection, whereas RT-PCR probably detected a previous but recent infection in the other HCW. Conclusio.n Based on the results of this pilot study, it is unlikely that RAT will reliably detect novel SARS-CoV-2 infections among asymptomatic HCWs despite serial sampling. Although RT-PCR-based screening of HCWs may not be feasible due to high sample volume, molecular methods may identify SARS-CoV-2-infected HCWs already during the presymptomatic stage. Keywords: SARS-CoV-2, health personnel, COVID-19 serological testing, real-time polymerase chain reaction, rapid antigen test, screening Published in DiRROS: 28.05.2021; Views: 1356; Downloads: 437 Link to file |
8. 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, original scientific article Abstract: 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. Keywords: food hypersensitivity, food intolerance, immunotherapy, immunology, food allergy, food allergens, oral immunotherapy Published in DiRROS: 15.02.2021; Views: 1624; Downloads: 1199 Full text (1,45 MB) This document has many files! More... |
9. Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategiesJean Bousquet, Jean-Paul Cristol, Wienczyslawa Czarlewski, Josep M. Antò i Boquè, Adrian Martineau, Tari Haahtela, Susana C. Fonseca, Guido Iaccarino, Hubert Blain, Alessandro Fiocchi, Nisera Bajrović, Natalija Edelbaher, Maja Jošt, Peter Kopač, Anja Koren, Mitja Košnik, Karmen Kramer Vrščaj, Samo Kreft, Nika Lalek, Bojan Madjar, Tonka Poplas-Susič, Irma Rozman Sinur, Tanja Soklič, Katja Triller Vadnal, Nadja Triller, Jure Urbančič, Mihaela Zidarn, 2020, review article Abstract: There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR[gamma]:Peroxisome proliferator-activated receptor, NF[kappa]B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2[alpha]:Elongation initiation factor 2[alpha]). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity. Keywords: Covid-19, SARS-CoV-2, food, insulin resistance, obesity, Nrf2, nutrients, TRPA1 Published in DiRROS: 25.01.2021; Views: 2120; Downloads: 736 Full text (1,61 MB) |
10. 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, original scientific article Abstract: 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. Keywords: allergy, allergen immunotherapy, B-cell epitope-based immunotherapy Published in DiRROS: 17.12.2020; Views: 1649; Downloads: 1006 Full text (3,82 MB) This document has many files! More... |