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Povzetek: 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 .
Ključne besede: immunology, drug allergy, anaphylaxis, antibiotics, monoclonal antibodies, α-tryptase, hereditary α-tryptasemia
Objavljeno v DiRROS: 18.06.2025; Ogledov: 144; Prenosov: 76
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Povzetek: 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) Downloadkeyboard_arrow_down Browse Figures Review Reports Versions Notes 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.
Ključne besede: mast cell activation test, LAD2, chronic spontaneous urticaria, omalizumab, CD63 expression
Objavljeno v DiRROS: 06.03.2025; Ogledov: 262; Prenosov: 153
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Povzetek: Allergen-specific venom immunotherapy (VIT) is a well-established therapy for Hymenoptera venom allergy (HVA). However, the precise mechanism underlying its clinical effect remains uncertain. Our study aimed to identify the molecular mechanisms associated with VIT efficiency. We prospectively included 19 patients with HVA undergoing VIT (sampled before the beginning of VIT, after reaching the maintenance dose, one year after finishing VIT, and after a sting challenge) and 9 healthy controls. RNA sequencing of whole blood was performed on an Illumina sequencing platform. Longitudinal transcriptomic profiling revealed the importance of the inhibition of the NFκB pathway and the downregulation of DUX4 transcripts for the early protection and induction of tolerance after finishing VIT. Furthermore, successful treatment was associated with inhibiting Th2, Th17, and macrophage alternative signalling pathways in synergy with the inhibition of the PPAR pathway and further silencing of the Th2 response. The immune system became activated when reaching the maintenance dose and was suppressed after finishing VIT. Finally, successful VIT restores the immune system’s balance to a state similar to that of healthy individuals. Our results underline the important role of the inhibition of four pathways in the clinical effect of VIT: Th2, Th17, NFκB, and macrophage signalling. Two biomarkers specific for successful VIT, regardless of the time of sampling, were C4BPA and RPS10-NUDT3 and should be further tested as potential biomarkers.
Ključne besede: Hymenoptera venom immunotherapy, longitudinal transcriptomic profiling, tolerance induction, successful venom immunotherapy
Objavljeno v DiRROS: 19.02.2025; Ogledov: 331; Prenosov: 186
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Povzetek: 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.
Ključne besede: allergy and immunology -- diagnosis, hypersensitivity -- diagnosis, skin tests, clinical epidemiology, baseline series, contact sensitization, patch tests, simultaneous reactivity
Objavljeno v DiRROS: 24.06.2022; Ogledov: 1275; Prenosov: 462
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Povzetek: 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.
Ključne besede: SARS-CoV-2, COVID-19, COVID-19 vaccines, allergens, anapylaxis, drug hypersensitivity
Objavljeno v DiRROS: 07.02.2022; Ogledov: 1861; Prenosov: 499
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