1. Evaluation of real-world mepolizumab use in severe asthma across Europe - the SHARP experience with privacy-preserving federated analysisJohannes A. Kroes, Rafael Alfonso-Cristancho, Aruna T. Bansal, Emmanuelle Berret, Kristina Bieksiene, Arnaud Bourdin, Luisa Brussino, Diogo Canhoto, Cristina Cardini, Gulfem Celik, Peter Kopač, Sabina Škrgat, 2023, original scientific article Abstract: Background: An objective of the severe heterogeneous asthma registry, patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking non-standardized, patient-level registry-data. Mepolizumab has shown clinical efficacy in RCTs and prospective real-world studies and could therefore serve as a proof of principle for this novel approach. The aim of the present study was to harmonise data from 10 national severe asthma registries and characterise patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns.
Methods: In this observational cohort study, registry data (5871 patients) were extracted for harmonisation. Where harmonisation was possible, patients who initiated mepolizumab between 1 January 2016 and 31 December 2021 were examined. Changes of a 12-month (range 11–18 months) period in frequent (two or more) exacerbations, maintenance OCS use and dose were analysed in a privacy-preserving manner using meta-analysis of generalised estimating equation parameters. Periods before and during the coronavirus disease 2019 pandemic were analysed separately.
Results: In 912 patients who fulfilled selection criteria, mepolizumab significantly reduced frequent exacerbations (OR 0.18, 95% CI 0.13–0.25), maintenance OCS use (OR 0.75, 95% CI 0.61–0.92) and dose (mean −3.93 mg·day−1, 95% CI −5.24–2.62 mg·day−1) in the pre-pandemic group, with similar trends in the pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns.
Conclusions: By harmonising patient-level registry data and applying federated analysis, SHARP demonstrated the real-world effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.
Published in DiRROS: 31.08.2026; Views: 54; Downloads: 32
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2. Epidemiologija in diagnostika perioperativnih alergijskih reakcij v SlovenijiŽiva Zidarn, Manica Voje, Elena Pelivanova, Peter Kopač, 2025, original scientific article Abstract: IZHODIŠČA. Perioperativne alergijske reakcije so redke. Večinoma se pojavijo nepričakovano, ni jih mogoče napovedati in imajo lahko resen potek. METODE. Gre za retrospektivno analizo bolnikov, ki so bili obravnavani v Alergološki enoti Klinike Golnik v letih 2017–2022. Analizirali smo demografske in klinične podatke ter potek alergološkega testiranja. REZULTATI. Diagnoza perioperativne alergijske reakcije je bila potrjena pri 56,6 %, sprožilec pa smo ugotovili pri 45,6 % obravnavanih bolnikov. Največ reakcij se je pojavilo med ortopedskimi posegi in med indukcijo anestezije. Najpogostejši alergeni so bili zaviralci živčno-mišičnega stika. Pri 30 % bolnikov je bila med reakcijo odvzeta kri za triptazo. Pri 19,4 % bolnikov, ki so doživeli perioperativno alergijsko reakcijo, kljub intenzivni alergološki diagnostiki sprožilec ni bil ugotovljen. RAZPRAVA. Glede na razpoložljive podatke je incidenca perioperativnih alergijskih reakcij v Sloveniji 8,7/1.000.000 letno, vendar je dejanska incidenca verjetno višja, saj vsi bolniki z alergijsko reakcijo niso bili testirani oz. niso bili vključeni v našo raziskavo. Zaradi nizkega deleža odvzetih vzorcev krvi za triptazo med reakcijo in relativno visokega deleža nepojasnjenih reakcij je treba izboljšati ozaveščenost zdravstvenega osebja in zagotoviti tesnejše sodelovanje med anesteziologi in alergologi.
Keywords: alergijska reakcija, incidenca, epidemiologija, diagnoza, zaviralci živčno-mišičnega stika, serumska triptaza
Published in DiRROS: 20.08.2026; Views: 201; Downloads: 71
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3. LAD2 mast cell activation test associates with the reaction severity and diagnoses BAT nonresponders in Hymenoptera venom allergy : LAD2 MAT in Hymenoptera venom allergyAna Koren, Luka Dejanović, Peter Kopač, Renato Eržen, Nisera Bajrović, Mihaela Zidarn, Peter Korošec, 2025, original scientific article Keywords: Basophil activation test nonresponders, Hymenoptera venom allergy, LAD2, mast cell activation test, reaction severity
Published in DiRROS: 07.08.2026; Views: 243; Downloads: 153
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4. Systemic immunologic effects of long-term dupilumab treatment in severe eosinophilic asthma beyond clinical outcomesSabina Škrgat, Luka Kunej, Urška Bidovec, Matevž Harlander, Saša Rink, Peter Korošec, Peter Kopač, 2026, original scientific article Abstract: Introduction: Dupilumab, an IL-4Rα antagonist that blocks IL-4/IL-13 signalling, is used in severe eosinophilic asthma to improve clinical control and suppress type 2 inflammation.Methods: We evaluated the clinical and systemic immunologic effects of dupilumab, focusing on type 2 biomarkers, total and aeroallergen-specific IgE, and FcεRI (High affinity IgE receptor) - expressing cells. Thirty-three adults with severe eosinophilic asthma were enrolled and followed up for 12 months in two Slovenian centres. Clinical assessments, spirometry, FeNO (Fractional exhaled nitric oxide), ACT (Asthma Control Test) scores, complete blood counts, total IgE, aeroallergen-specific IgE, and FcεRI expression on basophils were measured at baseline and at 1.5, 3, 6, and 12 months.Results: Twenty-seven patients completed follow-up and were included in the final analysis. Dupilumab treatment resulted in significant improvement in ACT (p = 0.0221), FEV1 (p = 0.0139) and reduction in exacerbations requiring OCS (oral corticosteroid) (p < 0.0001). FeNO declined by 78 %, total IgE by 83%, and aeroallergen-specific IgE by 65% with consistent reductions across perennial and seasonal allergens. Circulating eosinophils increased transiently, whereas basophils increased by 39%.Conclusions: Dupilumab demonstrated sustained clinical improvement in patients with severe eosinophilic asthma, accompanied by broad immunologic modulation. Concurrent reductions in FeNO, total IgE, and aeroallergen-specific IgE indicate upstream inhibition of IL-4/IL-13-mediated inflammation, suggesting modulation of the underlying type 2 inflammatory network.
Published in DiRROS: 23.07.2026; Views: 185; Downloads: 120
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5. Unmasking indolent systemic mastocytosis in patients with unexplained or treatment-refractory osteoporosis : a case series with diagnostic and therapeutic implicationsLucia Jankovski, Rok Herman, Matej Rakuša, Peter Kopač, Mark Kačar, Matevž Škerget, Andrej Janež, Mojca Jensterle Sever, 2026, original scientific article Abstract: Indolent systemic mastocytosis (ISM) is an under-recognised cause of secondary osteoporosis, and skeletal fragility may be the only presenting feature, delaying diagnosis. We describe four adults referred to a tertiary endocrinology service for unexplained osteoporosis or low-trauma fractures, in whom systemic mastocytosis (SM) was identified during work-up. All had elevated basal serum tryptase (41.4–87.0 µg/L), bone-marrow biopsy showing atypical mast cells and the KIT D816V variant; cutaneous lesions were absent in every case. Three patients fulfilled WHO 2022 criteria for ISM. The fourth had coexistent JAK2 V617F-positive post-essential-thrombocythaemia myelofibrosis and was classified as SM with associated haematological neoplasm (SM-AHN); his mast cell clone (tryptase 43.7 µg/L; KIT D816V VAF 0.391%) behaved indolently and contributed clinically through osteoporosis alone, illustrating that an indolent mast cell component can be overlooked when a chronic myeloid neoplasm dominates the picture. Presentations ranged from an isolated low-energy L5 fracture in a 55-year-old man, to multiple vertebral compression fractures despite denosumab in a 71-year-old woman with primary hyperparathyroidism, to severe wasp-sting anaphylaxis in a 43-year-old man. After multidisciplinary review, all received intravenous zoledronic acid with vitamin D repletion; KIT-targeted therapy is under consideration in selected patients. Although causal inferences cannot be drawn from four retrospectively identified cases, the series illustrates how ISM may be missed in unexplained or treatment-refractory osteoporosis—particularly in younger men, those with prior severe anaphylaxis, and those fracturing on antiresorptive therapy—and supports combining basal serum tryptase with high-sensitivity peripheral-blood KIT D816V testing, in line with the WHO/ICC/AIM-ECNM 2022–2024 criteria. Prospective studies are needed.
Keywords: indolent systemic mastocytosis, osteoporosis, bone mineral density
Published in DiRROS: 24.06.2026; Views: 272; Downloads: 222
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7. Markedly increased diamine oxidase during acute anaphylaxis is associated with an underlying clonal mast cell disorderMatija Rijavec, Žan Kogovšek, Jezerka Inkret, Peter Kopač, Peter Korošec, 2026, original scientific article Abstract: Introduction Diamine oxidase (DAO) degrades histamine, the key mediator in anaphylaxis, yet its relationship with clonal mast cell disorder (CMD) in the context of anaphylaxis is unclear. We evaluated whether DAO during anaphylaxis differs by CMD status. Methods We enrolled 35 emergency-department patients with acute anaphylaxis to drugs (7 patients), food (2 patients), or Hymenoptera venom (26 patients). Tryptase, DAO, and histamine degradation were measured during anaphylaxis and convalescence. CMD was defined by detecting KIT p.D816V in peripheral blood leukocytes using highly sensitive qPCR. Post-mortem DAO and tryptase were also compared in two fatal Hymenoptera venom-triggered anaphylaxis (HVA) cases with CMD versus 13 non-anaphylaxis controls. Results KIT p.D816V was detected in 6 (17%); all had severe HVA and normal basal tryptase. During anaphylaxis, DAO increased markedly in CMD (median 1142%), but only modestly in KIT p.D816V-negative patients (median 20%; p < 0.0001), independent of trigger or severity. Acute DAO was ~5-fold higher in CMD (median 101 vs. 18 U/mL), while convalescent DAO was similar (both 14 U/mL). Despite markedly elevated DAO, we observed impaired histamine degradation in acute anaphylaxis plasma. Receiver-operating-characteristic analyses showed strong discrimination for CMD using acute DAO (AUC 0.92; cut-off 53 U/mL; sensitivity 83%; specificity 97%) and percentage increase from convalescence (AUC 0.97; cut-off 223%; sensitivity 83%; specificity 100%). Post-mortem DAO lacked specificity, whereas post-mortem tryptase supported the diagnosis of fatal anaphylaxis and CMD. Conclusion DAO concentrations rise markedly during anaphylaxis in CMD and may help identify individuals at the highest risk. Further studies should refine the diagnostic utility and elucidate the mechanisms by which DAO may amplify anaphylaxis in CMD.
Keywords: anaphylaxis, clonal mast cell disorder, diamine oxidase, KIT p.D816V, tryptase
Published in DiRROS: 06.05.2026; Views: 258; Downloads: 318
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8. Newly diagnosed eosinophilic granulomatosis with polyangiitis in patients on biologics for severe asthma- a multi-centre case seriesHitasha Rupani, Aruna T. Bansal, Svetlana Sergejeva, Alexandra Nanzer, Marco Caminati, Peter Kopač, Zsuzsanna Csoma, Sabina Škrgat, Branislava Milenković, Kristina Bieksiene, Saša Rink, 2025, other scientific articles Keywords: alergology, severe asthma, biologics, EGPA
Published in DiRROS: 22.04.2026; Views: 363; Downloads: 437
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9. Targeting of the IL-5 pathway in severe asthma reduces mast cell progenitorsAbigail P. Alvarado-Vazquez, Erika Mendez-Enriquez, Maya Salomonsson, Peter Kopač, Ana Koren, Urška Bidovec, Sabina Škrgat, Oscar E. Simonson, Valentyina Yasinska, Peter Korošec, 2025, original scientific article Keywords: asthma, benralizumab, IL-5, mepolizumab, mast cells, mast cell progenitors
Published in DiRROS: 15.04.2026; Views: 391; Downloads: 338
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10. Epidemiology and management of malignancies in patients with inborn errors of immunity - an ESID registry study of 19,959 patientsDelfien J. A. Bogaert, Christina Helene Wolfsberger, Andishe Attarbaschi, Jonathan Gathmann, Klaus Warnatz, Gabriele Mueller, Anna Mukhina, Stephan Rusch, Gerhard Kindle, Joris M. van Montfrans, Markus G. Seidel, 2026, original scientific article Abstract: Background Inborn errors of immunity (IEI), or primary immune disorders (PIDs), predispose individuals to infections, autoimmunity, inflammation, allergy, and malignancy. Malignancies are a major cause of morbidity and mortality in patients with IEI/PIDs, with poorer outcomes compared with the general population. Objective We sought to determine the frequency and types of malignancies in patients with IEI/PIDs and to assess clinical management approaches across Europe. Methods Descriptive analyses were performed on malignancy data within each IEI category. In addition, a European Society for Immunodeficiencies Registry survey (05/2022-03/2024) collected data on management strategies and challenges. Results Of 19,959 patients with IEI/PIDs, 1783 (8.9%) developed malignancies, of whom 27.1% presented malignancy as first manifestation of IEI/PIDs. A total of 1210 malignancies were specified; B-cell non-Hodgkin lymphoma was most common (24.2%). Detailed malignancy-IEI/PID association maps are provided. Predominantly antibody deficiencies accounted for 59.1% of malignancy cases, with a higher median age at first malignancy (43.6 years) compared with other IEI/PID categories, for example, combined immunodeficiencies with syndromic or associated features (11.7 years). Survey findings revealed that oncological treatment was modified because of IEI/PIDs in 21.5% of cases, with assumed negative impacts of IEI/PIDs on complications and outcomes (in 27.4% and 30.7%, respectively). IEI/PIDs influenced transplant decisions in 16.5% of cases. Management practices such as interdisciplinary decision finding and guideline availability were recorded. Conclusions This study provides comprehensive epidemiological data on malignancies in IEI/PIDs, highlighting the need for tailored screening and management. Survey results emphasize the real-world challenges and support the development of IEI/PID-specific oncological surveillance guidelines and treatment strategies.
Keywords: inborn errors of immunity, IEI, primary immunodeficiency, PID, primary immune disorder, malignancy, cancer predisposition syndromes, tumor predisposition, ESID registry
Published in DiRROS: 08.04.2026; Views: 346; Downloads: 346
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