1. Genomic landscape of susceptibility to severe Covid-19 in the Slovenian populationAnja Kovanda, Tadeja Lukežič, Aleš Maver, Hana Vokač Križaj, Mojca Čižek-Sajko, Julij Šelb, Matija Rijavec, Barbara Bitežnik, Boštjan Rituper, Peter Korošec, Borut Peterlin, 2024, izvirni znanstveni članek Povzetek: Determining the genetic contribution of susceptibility to severe SARS-CoV-2 infection outcomes is important for public health measures and individualized treatment. Through intense research on this topic, several hundred genes have been implicated as possibly contributing to the severe infection phenotype(s); however, the findings are complex and appear to be population- dependent. We aimed to determine the contribution of human rare genetic variants associated with a severe outcome of SARS-CoV-2 infections and their burden in the Slovenian population. A panel of 517 genes associated with severe SARS-CoV-2 infection were obtained by combining an extensive review of the literature, target genes identified by the COVID-19 Host Genetic Initiative, and the curated Research COVID-19 associated genes from PanelApp, England Genomics. Whole genome sequencing was performed using PCR-free WGS on DNA from 60 patients hospitalized due to severe COVID-19 disease, and the identified rare genomic variants were analyzed and classified according to the ACMG criteria. Background prevalence in the general Slovenian population was determined by comparison with sequencing data from 8025 individuals included in the Slovenian genomic database (SGDB). Results show that several rare pathogenic/likely pathogenic genomic variants in genes CFTR, MASP2, MEFV, TNFRSF13B, and RNASEL likely contribute to the severe infection outcomes in our patient cohort. These results represent an insight into the Slovenian genomic diversity associated with a severe COVID-19 outcome.
Ključne besede: severe COVID-19, severe outcome of SARS-CoV-2 infection, whole-genome sequencing, genetic susceptibility, rare variants, human rare genomic variants
Objavljeno v DiRROS: 11.06.2026; Ogledov: 284; Prenosov: 230
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2. 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: 958; Prenosov: 614
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3. 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, izvirni znanstveni članek Povzetek: 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.
Ključne besede: phage panning, next-generation sequencing, bioinformatic analysis, allergen Ves v 5, epitopes
Objavljeno v DiRROS: 02.07.2025; Ogledov: 832; Prenosov: 697
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4. Remission of chronic urticaria in patients treated with omalizumabKlara Cvenkel, Mojca Bizjak-Šuran, Julij Šelb, Mitja Košnik, 2024, izvirni znanstveni članek Povzetek: Introduction: This study examined the remission probability and duration in chronic spontaneous urticaria (CSU) patients resistant to second-generation H1-antihistamines (sgAHs) undergoing omalizumab treatment.
Methods: This is a retrospective observational study of 176 adult CSU patients exhibiting a significant pruritus component (≥ 8) of the weekly urticaria activity score (UAS7) despite four daily sgAH tablets and starting omalizumab treatment with 300 mg every 4 weeks. After excluding 13 nonresponders, we analyzed 163 omalizumab responders (mean age 51.8 years, 74.4% female). The intervals between applications were increased. Discontinuation was considered for patients that remained asymptomatic on a gradually reduced dosage (to 150 mg every 12 weeks) without sgAHs.
Results: Omalizumab discontinuation was possible in 25.8% (42/163). The duration of omalizumab treatment before remission ranged from 7 to 6 months. Twenty-one patients (50.0%) maintained complete remission until the end of the observation period (September 2021) for 8 to 68 months. Of the relapsed patients, 71.4% (15/21) effectively controlled CSU with sgAHs. Six patients (28.6%; 6/21) required omalizumab reintroduction after 6 to 40 months of remission, responding favorably.
Conclusions: The study shows that a quarter of severe CSU patients achieve long-term remission. In addition, sgAHs effectively
manage symptoms in a majority of relapsed cases, and those requiring omalizumab reintroduction respond favorably.
Ključne besede: urticaria, antihistamines, omalizumab, urticaria, remission, urticaria relapse
Objavljeno v DiRROS: 16.06.2025; Ogledov: 822; Prenosov: 487
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5. 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, 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: 1110; Prenosov: 589
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8. Patients with detectable KIT p.D816V in peripheral blood are at high risk for adverse systemic events during venom immunotherapy and treatment failureAjda Demšar Luzar, Jakob Otorepec, Mitja Košnik, Peter Kopač, Julij Šelb, Peter Korošec, Matija Rijavec, 2024, izvirni znanstveni članek Ključne besede: immunology, allergy to poison Hymenoptera, peripheral leukocytes, venom immunotherapy
Objavljeno v DiRROS: 19.02.2025; Ogledov: 1165; Prenosov: 814
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9. 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, 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: 1719; Prenosov: 1162
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10. A novel mutation in the FOXC2 gene : a heterozygous insertion of adenosine (c.867insA) in a family with lymphoedema of lower limbs without distichiasisTanja Planinšek Ručigaj, Matija Rijavec, Jovan Miljković, Julij Šelb, Peter Korošec, 2017, izvirni znanstveni članek Ključne besede: primary lymphedema, FOXC2 mutation, distichiasis, lower limbs lymphedema
Objavljeno v DiRROS: 31.05.2024; Ogledov: 1485; Prenosov: 547
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