1. 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: 63; Downloads: 52
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2. 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, original scientific article Abstract: 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. Keywords: solid cancer, COVID-19 vaccination, booster third dose Published in DiRROS: 25.02.2026; Views: 369; Downloads: 192
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3. Editorial: genetic and immunological insights into angioedema without whealsMatija Rijavec, Maurizio Margaglione, Anastasios E. Germenis, 2026, other scientific articles Keywords: angioedema, biomarker, bradykinin, genetic, inflammatory mediators, outcome, real-world data, treatment Published in DiRROS: 30.01.2026; Views: 434; Downloads: 255
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4. 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, original scientific article Abstract: 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. Keywords: KIT D816V, hereditary α-tryptasemia, peripheral blood Published in DiRROS: 05.08.2025; Views: 762; Downloads: 507
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5. Combination of experimental and bioinformatic approaches for identification of immunologically relevant protein–peptide InteractionsJerneja Debeljak, Peter Korošec, Julij Šelb, Matija Rijavec, Mitja Košnik, Mojca Lunder, 2023, original scientific article Abstract: Protein–peptide interactions are an essential player in cellular processes and, thus, of great interest as potential therapeutic agents. However, identifying the protein’s interacting surface has been shown to be a challenging task. Here, we present a methodology for protein–peptide interaction identification, implementing phage panning, next-generation sequencing and bioinformatic analysis. One of the uses of this methodology is identification of allergen epitopes, especially suitable for globular inhaled and venom allergens, where their binding capability is determined by the allergen’s conformation, meaning their interaction cannot be properly studied when denatured. A Ph.D. commercial system based on the M13 phage vector was used for the panning process. Utilization of various bioinformatic tools, such as PuLSE, SAROTUP, MEME, Hammock and Pepitope, allowed us to evaluate a large amount of obtained data. Using the described methodology, we identified three peptide clusters representing potential epitopes on the major wasp venom allergen Ves v 5. Keywords: phage panning, next-generation sequencing, bioinformatic analysis, allergen Ves v 5, epitopes Published in DiRROS: 02.07.2025; Views: 672; Downloads: 575
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6. Hereditary α-tryptasemia is associated with anaphylaxis to antibiotics and monoclonal antibodiesPeter Korošec, Jonathan J. Lyons, Manca Svetina, Monika Koudová, Martina Bittóová, Mihaela Zidarn, Lenka Sedláčková, Matija Rijavec, Peter Kopač, 2025, original scientific article Abstract: 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 . Keywords: immunology, drug allergy, anaphylaxis, antibiotics, monoclonal antibodies, α-tryptase, hereditary α-tryptasemia Published in DiRROS: 18.06.2025; Views: 769; Downloads: 447
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7. Cold-induced anaphylaxis : new insights into clinical and genetic characteristicsMojca Bizjak-Šuran, Peter Korošec, Mitja Košnik, Julij Šelb, Urška Bidovec, Manca Svetina, Samo Zver, Dejan Dinevski, Matija Rijavec, 2025, original scientific article Abstract: 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). Keywords: anaphylaxis, cold urticaria, hereditary α-tryptasemia, KIT p.D816V, mast cell, total IgE, tryptase Published in DiRROS: 21.05.2025; Views: 932; Downloads: 476
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8. 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, original scientific article Abstract: 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. Keywords: thoracic malignancies, cancer therapy, COVID-19 vaccination, adverse events, breakthrough infection Published in DiRROS: 24.03.2025; Views: 1021; Downloads: 636
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10. Autoimmune mast cell activation test as a diagnostic tool in chronic spontaneous urticariaAna Koren, Luka Dejanović, Matija Rijavec, Peter Kopač, Mojca Bizjak-Šuran, Mihaela Zidarn, Mitja Košnik, Peter Korošec, 2024, original scientific article Abstract: 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)
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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. Keywords: mast cell activation test, LAD2, chronic spontaneous urticaria, omalizumab, CD63 expression Published in DiRROS: 06.03.2025; Views: 871; Downloads: 626
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