1. A three-dose mRNA COVID-19 vaccine regime produces both suitable immunogenicity and satisfactory efficacy in patients with solid cancersUrška Janžič, Urška Bidovec, Peter Korošec, Katja Mohorčič, Loredana Mrak, Marina Čakš, Maja Ravnik, Erik Škof, Matija Rijavec, 2023, izvirni znanstveni članek Povzetek: Background: The recommended booster third dose of vaccination against COVID-19 in cancer patients seems reasonable to protect them against a severe disease course. A prospective study was designed to assess the immunogenicity, efficacy, and safety of COVID-19 vaccination in this cohort. Methods: Patients with solid malignancies on active treatment were followed up after the primary course and booster third dose of vaccination to assess their anti-SARS-CoV-2 S1 IgG levels, efficacy in the case of SARS-CoV-2 infection, and safety. Results: Out of 125 patients receiving the primary course of vaccination, 66 patients received a booster third dose of mRNA vaccine, with a 20-fold increase in median anti-SARS-CoV-2 S1 IgG levels compared to Ab levels six months post-primary course of vaccination (p < 0.0001). After the booster third dose, anti-SARS-CoV-2 S1 IgG levels were comparable to healthy controls (p = 0.113). There was a decline in Ab levels 3 (p = 0.0003) and 6 months (p < 0.0001) post-third booster dose. No patients had either a severe disease course or a lethal outcome in the case of SARS-CoV-2 infection after the third booster dose. Conclusion: The third booster vaccination dose against COVID-19 in solid cancer patients triggers substantial immunogenicity and is safe and effective for preventing a severe COVID-19 disease course. Ključne besede: solid cancer, COVID-19 vaccination, booster third dose Objavljeno v DiRROS: 25.02.2026; Ogledov: 253; Prenosov: 142
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2. Cytokine profiles of bronchoalveolar lavage in patients with interstitial lung diseases and non-allergic asthmaDana Greif Lenarčič, Urška Bidovec, Pia Kristanc, Peter Kopač, Mateja Marc-Malovrh, Izidor Kern, Katarina Osolnik, 2025, izvirni znanstveni članek Povzetek: Diagnosing and prognosing immune-mediated airway diseases, like hypersensitivity pneumonitis (HP) and sarcoidosis, is complicated due to their overlapping symptoms and the lack of definitive biomarkers. Hence, we wanted to compare bronchoalveolar lavage (BAL) cytokine and chemokine profiles from 92 patients with different immune-mediated and inflammatory airway diseases, namely, HP, sarcoidosis, non-allergic asthma, amiodarone lung, and EGPA. We also compared pulmonary function parameters, BAL’s cellularity, and lymphocyte immunophenotypes. We found significant differences across all measured lung functions (VC, VC%, FEV1, FEV1%, and Tiff%) and in the number of macrophages, lymphocytes, neutrophils, and eosinophils. Furthermore, we showed significant differences in CD4, CD8, and CD4/8 across all included ILDs and OLDs; however, no significant differences were found in CD3, CD19, NK, or NKT. We identified nine biomarkers (IL-1β, IL-6, IL-8, IL-13, VEGF, angiogenin, C4a, RANTES, and MCP-1) that significantly differ in the BAL of patients with HP and sarcoidosis and showed that RANTES and IL-6 are associated with fibrotic outcome. We have demonstrated that interstitial and obstructive lung diseases differ in cytokine and cellular lung imprint, which may, in the future, enable the determination of the disease subtype and thus the identification of targets for the treatment of individuals or subgroups within diseases. Ključne besede: hypersensitivity pneumonitis, sarcoidosis, non-allergic asthma, amiodarone lung, EGPA, cytokines, bronchoalveolar lavage, chemokines, complement anaphylatoxins, angiogenesis-related factors Objavljeno v DiRROS: 05.08.2025; Ogledov: 700; Prenosov: 402
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3. Hereditary α − tryptasemia and peripheral blood KIT D816V mutation in patients with pediatric mastocytosisOlga Točkova, Tanja Planinšek Ručigaj, Simona Ivančan, Urška Bidovec, Matija Rijavec, Julij Šelb, 2025, izvirni znanstveni članek Povzetek: Hereditary α-tryptasemia (HαT)—a genetic trait caused by increased α-tryptase-encoding typtase alpha/beta-1 (TPSAB1) copy number—is associated with adult mastocytosis. The primary objective was to assess the association between α-tryptase and pediatric mastocytosis. We also want to evaluate whether the KIT p.D816V mutation in peripheral blood leukocytes (PBLs) reliably predicts systemic mastocytosis (SM) in children. A prospective cohort of 68 children from a referral center in Slovenia with cutaneous mastocytosis (CM) underwent tryptase genotyping by droplet digital PCR and examination for KIT p.D816V in PBL using a sensitive PCR test. A significant majority of patients (57 of 68; [83.8%]) had at least one α-tryptase-encoding gene; none had HαT. 7 of the 68 (10.3%) who were positive for KIT p.D816V in PBL, one fulfilled diagnostic criteria for indolent SM, and another was diagnosed with monoclonal mast cell activation syndrome. One of those individuals had an increased basal serum tryptase (BST) level (14.5 ng/mL). We found a high presence of germline α-tryptase in children with CM, but not HαT. By employing sensitive examination for KIT p.D816V in PBL, in combination with clinical data and other examinations, our study suggests that KIT p.D816V in PBL may indicate systemic disease in children with CM. Ključne besede: KIT D816V, hereditary α-tryptasemia, peripheral blood Objavljeno v DiRROS: 05.08.2025; Ogledov: 686; Prenosov: 454
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4. Basophil activation test predicts cetuximab anaphylaxis severity in alpha-gal IgE-positive patientsPeter Kopač, Ana Koren, Urška Bidovec, Mitja Košnik, Luka Dejanović, Tanja Mesti, Primož Strojan, Peter Korošec, Janja Ocvirk, 2024, izvirni znanstveni članek Povzetek: Upon first exposure to cetuximab, hypersensitivity reactions can occur. We aimed to assess the utility of the basophil activation test (BAT) to alpha-gal and cetuximab for predicting severe reactions. We prospectively recruited 38 patients and evaluated sIgE to alpha-gal in all patients before the first application of cetuximab. In all alpha-gal-sensitized patients, we evaluated skin tests to meat extracts, gelatine, and cetuximab and performed BAT with alpha-gal and cetuximab. In 24% (9/38) of patients, sIgE to alpha-gal was >0.10 kUA/L, and 8/9 reacted to the cetuximab. Basophil activation tests with alpha-gal were positive in all sensitized patients and were higher in those with severe reactions (18.3% in grade 4 [n = 4] vs. 1.8% in grade 2 [n = 3] or no reaction [n = 1] at 3.3 ng/mL of alpha-gal; p = 0.03). All patients with severe grade 4 reactions had a positive CD63 BAT response to cetuximab compared to patients with moderate or no reaction, who all had negative BAT (57.7% vs. 0.9% at 500 µg/mL, 63.2% vs. 4.1% at 100 µg/mL, 58.2% vs. 2.7% at 10 µg/mL, and 32.1% vs. 3.3% at 1 µg/mL of cetuximab, respectively; p ≤ 0.001). In summary, before initiating cetuximab treatment, sIgE to alpha-gal should be assessed in all patients. To predict the severity of the reaction and to assess the risk of cetuximab-induced anaphylaxis, we should perform BATs with alpha-gal or more discriminative BATs with cetuximab. Ključne besede: alpha-gal, baseline serum tryptase, basophil activation test, cetuximab, drug allergy Objavljeno v DiRROS: 22.07.2025; Ogledov: 942; Prenosov: 469
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5. Fibulin-3 in plasma and pleural effusion as a biomarker of mesotheliomaKatja Adamič, Mateja Marc-Malovrh, Urška Bidovec, Aleš Rozman, 2025, izvirni znanstveni članek Povzetek: Background: Malignant pleural mesothelioma (MPM) is a global health concern linked to asbestos exposure. In Slovenia, regions with high asbestos exposure rates make MPM a significant public health issue. Although thoracoscopic biopsy is the gold standard for MPM diagnosis, its invasiveness highlights the need for reliable, non-invasive diagnostic biomarkers. Patients and Methods: This prospective study evaluated the diagnostic potential of fibulin-3 as a biomarker for MPM, focusing on its ability to distinguish MPM from other pleural conditions, its association with disease stage and histological subtype, and its prognostic value for survival. 90 patients who underwent diagnostic thoracoscopic biopsy from January 2013 to October 2014 were included. Fibulin-3 levels in plasma and pleural effusion were measured using ELISA, and clinical data were analysed with statistical tests, including ROC analysis. Results: The study cohort comprised 32 patients with MPM, 24 with metastatic pleural carcinoma, and 34 with benign pleural diseases. Plasma fibulin-3 levels were significantly elevated (p = 0.0132) in MPM patients compared to those with benign pleural effusions due to asbestos exposure, with a cut-off of 12.31 ng/mL showing 100% specificity but low sensitivity (39.39%). Elevated fibulin-3 levels in pleural effusion correlated with advanced disease (p = 0.0463) and aggressive histological subtypes (p = 0.0324). No significant survival correlation was observed. Conclusions: While plasma fibulin-3 is a highly specific biomarker for MPM, its low sensitivity limits its standalone diagnostic utility. Its potential role in risk stratification and early detection in at-risk populations warrants further study. Ključne besede: fibulin-3, asbestos, pleural effusion, mesothelioma, biomarker Objavljeno v DiRROS: 18.06.2025; Ogledov: 661; Prenosov: 339
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6. Cold-induced anaphylaxis : new insights into clinical and genetic characteristicsMojca Bizjak, Peter Korošec, Mitja Košnik, Julij Šelb, Urška Bidovec, Manca Svetina, Samo Zver, Dejan Dinevski, Matija Rijavec, 2025, izvirni znanstveni članek Povzetek: The pathogenesis of cold urticaria (ColdU) and cold-induced anaphylaxis (ColdA) remains poorly understood, and ColdA is underrepresented in anaphylaxis literature. Laboratory features to guide management are largely unknown. This study evaluated basal serum tryptase (BST) and total immunoglobulin E (IgE) levels in ColdU and ColdA, their associations with clinical features, and the utility of testing for the KIT p.D816V variant in blood leukocytes and hereditary a-tryptasemia (HaT). Ključne besede: anaphylaxis, cold urticaria, hereditary α-tryptasemia, KIT p.D816V, mast cell, total IgE, tryptase Objavljeno v DiRROS: 21.05.2025; Ogledov: 877; Prenosov: 417
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7. Prospective observational study of COVID-19 vaccination in patients with thoracic malignancies : adverse events, breakthrough infections and survival outcomesUrška Janžič, Andrej Janžič, Abed Agbarya, Urška Bidovec, Katja Mohorčič, Marina Čakš, Peter Korošec, Matija Rijavec, Erik Škof, 2024, izvirni znanstveni članek Povzetek: Abstract: Due to the devastating COVID-19 pandemic, a preventive tool in the form of vaccination was introduced. Thoracic cancer patients had one of the highest rates of morbidity and mortality due to COVID-19 disease, but the lack of data about the safety and effectiveness of vaccines in this population triggered studies like ours to explore these parameters in a cancer population. Out of 98 patients with thoracic malignancies vaccinated per protocol, 60–75% experienced some adverse events (AE) after their first or second vaccination, most of them were mild and did not interfere with their daily activities. Out of 17 severe AEs reported, all but one were resolved shortly after vaccination. No significant differences were noted considering AE occurrence between different cancer therapies received after the first or second vaccination dose, p = 0.767 and p = 0.441, respectively. There were 37 breakthrough infections either after the first (1), second (13) or third (23) vaccine dose. One patient died as a direct consequence of COVID-19 infection and respiratory failure, and another after disease progression with simultaneous severe infection. Eight patients had moderate disease courses, received antiviral therapies and survived without consequences. Vaccination did not affect the time to disease progression or death from underlying cancer. Ključne besede: thoracic malignancies, cancer therapy, COVID-19 vaccination, adverse events, breakthrough infection Objavljeno v DiRROS: 24.03.2025; Ogledov: 958; Prenosov: 584
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8. 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: 910; Prenosov: 647
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9. Art v 1 IgE epitopes of patients and humanized mice are conformationalMaja Zabel, Milena Weber, Bernhard Kratzer, Cordula Köhler, Beatrice Jahn-Schmid, Gabriele Gadermaier, Pia Gattinger, Urška Bidovec, Peter Korošec, Ursula Smole, Rudolf Valenta, Winfried F. Pickl, 2022, izvirni znanstveni članek Povzetek: Background: Worldwide, pollen of the weed mugwort (Artemisia vulgaris) is a major cause of severe respiratory allergy, with its major allergen, Art v 1, being the key pathogenic molecule for millions of patients. Humanized mice transgenic for a human T-cell receptor specific for the major Art v 1 T-cell epitope and the corresponding HLA have been made. Objective: We sought to characterize IgE epitopes of Art v 1–sensitized patients and humanized mice for molecular immunotherapy of mugwort allergy. Methods: Four overlapping peptides incorporating surface-exposed amino acids representing the full-length Art v 1 sequence were synthesized and used to search for IgE reactivity to sequential epitopes. For indirect mapping, peptide-specific rabbit antibodies were raised to block IgE against surface-exposed epitopes on folded Art v 1. IgE reactivity and basophil activation studies were performed in clinically defined mugwort-allergic patients. Secondary structure of recombinant (r) Art v 1 and peptides was determined by circular dichroism spectroscopy. Results: Mugwort-allergic patients and humanized mice sensitized by allergen inhalation showed IgE reactivity and/or basophil activation mainly to folded, complete Art v 1 but not to unfolded, sequential peptide epitopes. Blocking of allergic patients’ IgE with peptide-specific rabbit antisera identified a hitherto unknown major conformational IgE binding site in the C-terminal Art v 1 domain. Conclusions: Identification of the new major conformational IgE binding site on Art v 1, which can be blocked with IgG raised against non-IgE reactive Art v 1 peptides, is an important basis for the development of a hypoallergenic peptide vaccine for mugwort allergy. Ključne besede: mugwort pollen allergy, IgE epitope, allergen-specific immunotherapy Objavljeno v DiRROS: 31.08.2022; Ogledov: 2196; Prenosov: 939
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10. Solid cancer patients achieve adequate immunogenicity and low rate of severe adverse events after SARS-CoV-2 vaccinationUrška Janžič, Urška Bidovec, Katja Mohorčič, Loredana Mrak, Nina Fokter Dovnik, Marija Ivanović, Maja Ravnik, Marina Čakš, Erik Škof, Jerneja Debeljak, Peter Korošec, Matija Rijavec, 2022, izvirni znanstveni članek Povzetek: Background: SARS-CoV-2 vaccination in cancer patients is crucial to prevent severe COVID-19 disease course. Methods: This study assessed immunogenicity of cancer patients on active treatment receiving mRNA-based SARS-CoV-2 vaccine by detection of anti-SARS-CoV-2 S1 IgG antibodies in serum, before, after the first and second doses and 3 months after a complete primary course of vaccination. Results were compared with healthy controls. Results: Of 112 patients, the seroconversion rate was 96%. A significant reduction in antibody levels was observed 3 months after vaccination in patients receiving immune checkpoint inhibitors versus control participants (p < 0.001). Adverse events were mostly mild. Conclusion: Immunogenicity after mRNA-based vaccine in cancer patients is adequate but influenced by the type of anticancer therapy. Antibody levels decline after 3 months, and thus a third vaccination is warranted. Ključne besede: onkološko zdravljenje, imunogenost, osnovno cepljenje mRNA, čvrsti tumorji, anticancer treatment, immunogenicity, mRNA-based vaccination, solid cancer Objavljeno v DiRROS: 24.06.2022; Ogledov: 2239; Prenosov: 967
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