Sintayehu Ambachew, Mahnaz Ramezanpour, Clare M Cooksley, Gohar Shaghayegh, Isabella Burdon, Emma F Barry, Kevin Aaron Fenix, P J Wormald, Alkis J Psaltis, Sarah Vreugde
{"title":"Staphylococcus aureus and Staphylococcus lugdunensis Act in Concert to Disrupt the Nasal Epithelial Barrier.","authors":"Sintayehu Ambachew, Mahnaz Ramezanpour, Clare M Cooksley, Gohar Shaghayegh, Isabella Burdon, Emma F Barry, Kevin Aaron Fenix, P J Wormald, Alkis J Psaltis, Sarah Vreugde","doi":"10.1002/clt2.70177","DOIUrl":"10.1002/clt2.70177","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic rhinosinusitis (CRS) pathophysiology and its link to microbiome is an area of ongoing investigation. Certain pathogens, in particular Staphylococcus aureus described to contribute to recalcitrant CRS. In addition, different species of coagulase negative staphylococci (CoNS) are frequently isolated from the sinonasal cavity of CRS patients. However, the influence of Staphylococcal species coexisting in the same niche on the inflammatory process remains unclear. The aim of this study was to explore the impact of exoproteins from various Staphylococcus species isolated from the same patients on the mucosal barrier.</p><p><strong>Methods: </strong>Staphylococcal species isolated from CRS and control patients were cultured from sinus swabs in planktonic and biofilm forms, and their exoproteins extracted. Primary human nasal epithelial cells (HNECs) from CRS patients were cultured at an air-liquid interface (ALI) and exposed to 20 μg/mL exoproteins or control. Barrier disruption and cytotoxicity were assessed by measuring the transepithelial electrical resistance (TEER), passage of fluorescein labeled dextrans and lactate dehydrogenase (LDH) levels. IL- 6 concentration was measured employing ELISA. Patient's matched sinonasal tissue samples were analyzed with flow cytometry to detect and quantify immune cells.</p><p><strong>Results: </strong>Forty-four Staphylococcal species were isolated from 22 CRS and control patients including: 22 S. aureus, 12 S. epidermidis, and 10 S. lugdunensis. 15 out of 22 S. aureus exoproteins significantly enhanced cytotoxicity, reduced TEER values and increased paracellular permeability compared to control (p < 0.05). By contrast, S. epidermidis and S. lugdunensis exoproteins caused either mild or negligible effects on the TEER values, cell viability, and paracellular permeability. However, S. lugdunensis exoproteins induced significantly higher IL-6 compared to control. Correlation analysis indicated S. aureus and S. lugdunensis from the same patient acted in concert to disrupt the nasal epithelial barrier and induce toxicity.</p><p><strong>Conclusion: </strong>This study shows the significant and detrimental impact of the presence of S. aureus exoproteins on nasal epithelial cell barrier function. S. aureus and S. lugdunensis isolated from the same patients acted in concert to affect the nasal barrier and inducing toxicity.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"16 5","pages":"e70177"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13239409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148004947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Francesca Perego, Azzurra Cesoni Marcelli, Riccardo Senter, Lorenza Chiara Zingale, Antonio Gidaro, Valentina Popescu Janu, Francesco Arcoleo, Pietro Andrea Accardo, Mariangela Lo Pizzo, Andrea Zanichelli, Francesco Giardino, Andrea Caruso, Simone Giosuè Longhitano, Edoardo Cataudella, Alessandra Vultaggio, Andrea Matucci, Angelica Petraroli, Roberta Gatti, Giuseppe Spadaro, Luisa Brussino, Stefania Nicola, Luca Lo Sardo, Maria Domenica Guarino, Federica Ruin, Luca Ranucci, Donatella Bignardi, Marica Giliberti, Paolo Borrelli, Paola Triggianese, Massimo Triggiani, Caterina Colangelo, Paola Lucia Minciullo, Tiziana Maria Angela De Pasquale, Chiara Beatrice Cogliati, Giada De Angeli, Davide Firinu, Vincenzo Montinaro, Mauro Cancian
{"title":"The Neglected Older Adults in Hereditary Angioedema: Insights From the ITACA Registry.","authors":"Francesca Perego, Azzurra Cesoni Marcelli, Riccardo Senter, Lorenza Chiara Zingale, Antonio Gidaro, Valentina Popescu Janu, Francesco Arcoleo, Pietro Andrea Accardo, Mariangela Lo Pizzo, Andrea Zanichelli, Francesco Giardino, Andrea Caruso, Simone Giosuè Longhitano, Edoardo Cataudella, Alessandra Vultaggio, Andrea Matucci, Angelica Petraroli, Roberta Gatti, Giuseppe Spadaro, Luisa Brussino, Stefania Nicola, Luca Lo Sardo, Maria Domenica Guarino, Federica Ruin, Luca Ranucci, Donatella Bignardi, Marica Giliberti, Paolo Borrelli, Paola Triggianese, Massimo Triggiani, Caterina Colangelo, Paola Lucia Minciullo, Tiziana Maria Angela De Pasquale, Chiara Beatrice Cogliati, Giada De Angeli, Davide Firinu, Vincenzo Montinaro, Mauro Cancian","doi":"10.1002/clt2.70171","DOIUrl":"10.1002/clt2.70171","url":null,"abstract":"<p><strong>Background: </strong>Hereditary Angioedema due to C1-inhibitor deficiency (HAE-C1INH) is a rare disease that affects individuals of all ages, however, older adults have never been characterized in terms of disease severity, comorbidities, and treatments. The aim was to identify the clinical characteristics of and therapeutic approaches in HAE-C1INH patients aged 65 and older.</p><p><strong>Methods: </strong>Data from the ITACA (Italian network for Hereditary and Acquired Angioedema) Registry were prospectively collected for 10-month.</p><p><strong>Results: </strong>Data from 647 HAE-C1INH, patients including 343 females (53%), were collected: 114 patients (17.6%) were aged 65 and older (68 females; 58.6%). Group mean age was 74.3 ± 7.5 years, mean age at first-symptom-onset was 19 ± 15 years, and mean age at diagnosis was 45.6 ± 14.3 years. Common comorbidities were: hypertension (59.6%), dyslipidaemia (28.9%), coronary artery disease (14.0%), diabetes (14.0%), endocrinopathies (14.0%), neoplasia (12.3%) and B/C hepatitis (11.4%). Half of the older patients (49%) experienced at least one attack during the study period, and 8 patients (7%) had an attack frequency of > 0.5 attacks/month. Long-term prophylaxis (LTP) was the treatment of choice in 45 patients (39.5%) and represented 15.9% of overall LTP prescriptions: 60% were treated with lanadelumab, 22.2% with attenuated androgens, 13.3% with berotralstat, and 4.5% with sub-cutaneous C1INH concentrate. Gender differences were not detected in any of the variables analyzed.</p><p><strong>Conclusion: </strong>Older patients with HAE-C1INH constitute a relevant subgroup, characterized by persistent disease activity and comorbidities. The availability of new therapies and guideline recommendations are driving an increase in LTP use, although shifting from older non-specific treatments, especially androgens, is still incomplete.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"16 5","pages":"e70171"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147986906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gizem Koken, H Ilbilge Ertoy Karagol, Sinem Polat Terece, Ceren Varer Akpinar, Kenan Cetin, Zeynep Cavdar, Berkehan Kara, A Kubra Baskin, Arzu Bakirtas
{"title":"Biphasic, Refractory, and Persistent Anaphylaxis in Children.","authors":"Gizem Koken, H Ilbilge Ertoy Karagol, Sinem Polat Terece, Ceren Varer Akpinar, Kenan Cetin, Zeynep Cavdar, Berkehan Kara, A Kubra Baskin, Arzu Bakirtas","doi":"10.1002/clt2.70174","DOIUrl":"10.1002/clt2.70174","url":null,"abstract":"<p><strong>Background: </strong>A Delphi consensus report refined anaphylaxis phenotypes as biphasic, refractory, and persistent anaphylaxis (BA, RA, and PA). To date, no study in either pediatric or adult populations has comprehensively evaluated the full spectrum of anaphylaxis phenotypes as outlined in this consensus. The primary aim of this study was to identify these phenotypes and compare them with conventional anaphylaxis in children.</p><p><strong>Methods: </strong>Patients aged ≤ 18 years who were diagnosed with or followed up for anaphylaxis at our department over the past 15 years were retrospectively screened for this study. All anaphylaxis cases were categorized as conventional anaphylaxis (Group 1) or as BA, RA, and PA phenotypes (Group 2). A comparative analysis was conducted between Group 1 and Group 2 with respect to demographics, triggers, clinical features, severity, management, and outcomes.</p><p><strong>Results: </strong>A total of 393 patients and 529 anaphylaxis episodes were included. Twenty-six (6.6%) of all anaphylaxis cases were classified as BA (3.5%), RA (1.5%), or PA (1.5%). For BA, the median time to recurrence of symptoms and signs was 4 h (1-24 h), whereas the median duration of PA manifestations was 4 h (4-6 h). These phenotypes (Group 2) were more common in older children and were associated with increased cardiovascular manifestations, greater severity, and higher use of systemic corticosteroid (p < 0.001). They did not differ significantly from Group 1 with respect to gender, comorbidities, family history of atopy, timing or location of the anaphylaxis, or number of episodes. Drugs, followed by venoms, were more frequent triggers in Group 2, whereas food was significantly more common in Group 1 (p < 0.05). IM adrenaline was administered in 69.2% of Group 2 and 52.3% of Group 1, with no significant difference (p > 0.05). Comparisons among BA, RA, and PA could not be performed due to the limited sample size within each phenotype.</p><p><strong>Conclusions: </strong>BA, RA, and PA are rare anaphylaxis phenotypes, more frequently drug or venom induced, seen at older ages, with ongoing gaps in proper IM adrenaline use.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"16 5","pages":"e70174"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Systemic Nickel Allergy Syndrome: A Critical Appraisal of an Unvalidated Diagnostic Entity.","authors":"Antonello Giovannetti","doi":"10.1002/clt2.70169","DOIUrl":"10.1002/clt2.70169","url":null,"abstract":"<p><p>Systemic Nickel Allergy Syndrome (SNAS) remains a controversial clinical construct, characterized by persistent diagnostic uncertainty and the absence of reproducible biomarkers. Available studies are predominantly limited to small case series and uncontrolled observational reports, yielding partial and inconclusive findings. Diagnostic approaches, including oral provocation tests, frequently employ nickel exposures that far exceed typical dietary intake, raising concerns regarding physiological relevance and methodological validity. Finally, scientific inquiry into this entity has largely neglected crucial aspects such as nickel bioavailability and bioaccessibility. Against this background, particularly within the Italian clinical context, SNAS has received considerable medical and public attention despite the limited and inconsistent evidence supporting its recognition as a systemic allergic condition. Reported clinical improvements following low-nickel diets are more plausibly explained by non-specific dietary modifications-such as reduced intake of fermentable carbohydrates-rather than by a targeted immunological response to nickel. In conclusion, SNAS does not fulfill the criteria required for recognition as a discrete pathological entity. Rather, it represents a unvalidated diagnostic label for non-specific symptoms shared across established functional syndromes.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":"16 5","pages":"e70169"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}