{"title":"Infants and toddlers with sensitization to peanut are often co-sensitized to tree nuts","authors":"Lara Meixner, Stephanie Heller, Friederike Bluhme, Valérie Trendelenburg, Kirsten Beyer, Birgit Kalb","doi":"10.1002/clt2.70008","DOIUrl":"10.1002/clt2.70008","url":null,"abstract":"<p>To the Editor,</p><p>Especially infants with eczema are at high risk for developing food allergies and it is the current understanding that sensitization occurs via the cutaneous route due to an impaired skin barrier function.<span><sup>1, 2</sup></span> Accordingly, a high peanut consumption in the household has been shown to be a possible risk factor for developing peanut allergy in infancy.<span><sup>3</sup></span> Therefore, German S3-guidelines on allergy prevention recommend that peanut allergy should first be ruled out in infants with moderate to severe atopic dermatitis, before introducing peanut into the infant's diet for preventive purposes.<span><sup>4</sup></span> During the last decades, vegan and plant-based diets have become a growing trend.<span><sup>5</sup></span> Tree nuts, such as cashews, hazelnuts and walnuts are a nutritional mainstay of plant-based diets and plant-based alternatives for milk and milk-products often contain tree nuts.<span><sup>5</sup></span> These changes in dietary habits may lead to a wider spread of tree nut allergens in households, increasing the risk for cutaneous exposure. There are hints, that individuals with peanut allergy have a higher likelihood of being allergic to tree nuts compared to the general population.<span><sup>6, 7</sup></span> Therefore, the aim of this study was to investigate how often peanut-sensitized infants and toddlers are sensitized to cashew, hazelnut and walnut as well as their seed storage proteins, which might be associated with a high risk for clinical reactivity.</p><p>The study cohort consists of infants and toddlers who were referred to the Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité—Universitätsmedizin Berlin. Some of the patients underwent an oral food challenge (OFC) for routine diagnostics between 2007 and 2020. Blood as well as clinical data was collected from all patients in the frame of routine diagnostics. Inclusion criteria for the analysis of co-sensitization was age ≤2 years and specific IgE (sIgE) to peanut ≥0.1 kU/l.</p><p>The detection of sIgE to peanut, hazelnut, walnut and cashew and to their respective 2S albumins Ara h 2, Cor a 14, Jug r 1, Ana o 3 as well as to the 7S vicilin-like globulin Ara h 1, was performed by using the NOVEOS<sup>TM</sup> immunoanalyzer (Garden Grove, California, USA). Sensitization was defined as sIgE ≥0.1 kU/l.</p><p>In order to determine the probability for a positive hazelnut food challenge by Cor a 14-sIgE and for a positive cashew food challenge by Ana o 3-sIgE for each patient, probability curves by Beyer et al. and Lange et al. were utilized.<span><sup>8, 9</sup></span> Since there is no probability curve available for walnut, the individual risk for a positive OFC with walnut could not be estimated (see Supporting Information S1 for detailed methods).</p><p>Sera from 101 peanut-sensitized patients (peanut-sIgE ≥0.1 kU/l) were analyzed. The median age of the patients a","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582264","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}
Torsten Zuberbier, Antonella Muraro, Ulugbek Nurmatov, Stefania Arasi, Katarina Stevanovic, Aikaterini Anagnostou, Roberta Bonaguro, Sharon Chinthrajah, Gideon Lack, Alessandro Fiocchi, Thuy-My Le, Paul Turner, Montserrat Alvaro Lozano, Elizabeth Angier, Simona Barni, Phillippe Bégin, Barbara Ballmer-Weber, Victoria Cardona, Carsten Bindslev-Jensen, Antonella Cianferoni, Nicolette de Jong, Debra de Silva, Antoine Deschildre, Audrey Dunn Galvin, Motohiro Ebisawa, David M Fleischer, Jennifer Gerdts, Mattia Giovannini, Josefine Gradman, Susanne Halken, Syed Hasan Arshad, Ekaterina Khaleva, Susanne Lau, Richard Loh, Mika J Mäkelä, Mary Jane Marchisotto, Laura Morandini, Charlotte G Mortz, Caroline Nilsson, Anna Nowak-Wegrzyn, Marcia Podestà, Lars K Poulsen, Graham Roberts, Pablo Rodríguez Del Río, Hugh A Sampson, Angel Sánchez, Sabine Schnadt, Peter K Smith, Hania Szajewska, Natasa Teovska Mitrevska, Alice Toniolo, Carina Venter, Amena Warner, Gary W K Wong, Robert Wood, Margitta Worm
{"title":"GA<sup>2</sup>LEN ANACARE consensus statement: Potential of omalizumab in food allergy management.","authors":"Torsten Zuberbier, Antonella Muraro, Ulugbek Nurmatov, Stefania Arasi, Katarina Stevanovic, Aikaterini Anagnostou, Roberta Bonaguro, Sharon Chinthrajah, Gideon Lack, Alessandro Fiocchi, Thuy-My Le, Paul Turner, Montserrat Alvaro Lozano, Elizabeth Angier, Simona Barni, Phillippe Bégin, Barbara Ballmer-Weber, Victoria Cardona, Carsten Bindslev-Jensen, Antonella Cianferoni, Nicolette de Jong, Debra de Silva, Antoine Deschildre, Audrey Dunn Galvin, Motohiro Ebisawa, David M Fleischer, Jennifer Gerdts, Mattia Giovannini, Josefine Gradman, Susanne Halken, Syed Hasan Arshad, Ekaterina Khaleva, Susanne Lau, Richard Loh, Mika J Mäkelä, Mary Jane Marchisotto, Laura Morandini, Charlotte G Mortz, Caroline Nilsson, Anna Nowak-Wegrzyn, Marcia Podestà, Lars K Poulsen, Graham Roberts, Pablo Rodríguez Del Río, Hugh A Sampson, Angel Sánchez, Sabine Schnadt, Peter K Smith, Hania Szajewska, Natasa Teovska Mitrevska, Alice Toniolo, Carina Venter, Amena Warner, Gary W K Wong, Robert Wood, Margitta Worm","doi":"10.1002/clt2.70002","DOIUrl":"10.1002/clt2.70002","url":null,"abstract":"<p><p>Immunoglobulin E (IgE)-mediated food allergies are the most common type of food allergy, often causing rapid symptoms after exposure to allergens posing a serious health risk and a high impact on patient's and caregiver's quality of life. Omalizumab, a humanized anti-IgE monoclonal antibody, reduces allergic reactions by binding to circulating IgE. Omalizumab has been successfully used in allergic asthma, chronic rhinosinusitis with nasal polyps, and chronic urticaria, and was recently approved for treating IgE-mediated food allergies by the US Food and Drug Administration (FDA). This GA<sup>2</sup>LEN ANACARE Consensus Statement presents our position on the use of omalizumab for treating IgE-mediated food allergies, based on a systematic review and meta-analysis, experience with use for other conditions, and expert consensus achieved via an eDelphi process. Following publication of the recent OUtMATCH study (stage 1) results and subsequent FDA approval, we propose that there is now sufficient evidence to recommend omalizumab as the only drug currently available that can mechanistically reduce IgE-mediated food allergic reactions. We acknowledge that the evidence does not reach the highest level of evidence which would be needed for a guideline recommendation.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590263","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}
Ruperto González-Pérez, Paloma Poza-Guedes, María Gabriela Martín-Voso, Inmaculada Sánchez-Machín
{"title":"Evaluation of real-world efficacy of mepolizumab on SNOT-22 outcomes in patients with unified airway disease","authors":"Ruperto González-Pérez, Paloma Poza-Guedes, María Gabriela Martín-Voso, Inmaculada Sánchez-Machín","doi":"10.1002/clt2.70006","DOIUrl":"10.1002/clt2.70006","url":null,"abstract":"<p>To the Editor,</p><p>The unified airway hypothesis suggests that the upper and lower airways constitute a single, interconnected organ, sharing significant physiological traits such as immunology, pathophysiology, epidemiology, and clinical features.<span><sup>1</sup></span> Allergic rhinitis (AR), various forms of chronic rhinosinusitis (CRS), including those with nasal polyposis (NP), and severe asthma (SA) share a common underlying pathogenesis known as type-2 inflammation (T2).<span><sup>2</sup></span> These coexisting conditions represent a substantial clinical burden and significantly impact patients' quality of life (QoL) through a variety of disruptive symptoms The SNOT-22 is a validated questionary designed to assess the symptom burden of CRS and has proven effective utility in evaluating both QoL and symptom control in AR.<span><sup>3, 4</sup></span></p><p>Mepolizumab, a monthly subcutaneous IL-5 antagonist monoclonal antibody, has been approved for treating various type 2 inflammatory conditions, including both eosinophilic SA and CRSwNP.<span><sup>5, 6</sup></span> The performance of mepolizumab on SNOT-22 scores has not been completely assessed in patients afflicted with Unified Airway Disease (UAD).</p><p>This Phase IV, single-center observational cohort investigation, conducted at Hospital Universitario de Canarias in Tenerife, Spain, aimed to evaluate the real-world performance of mepolizumab 100 mg every 4 weeks (100 mg-q4w) over 52-weeks on SNOT-22 scores in patients aged over 18 years with UAD, including uncontrolled SA and persistent mite (<i>Dermatophagoides spp</i>. and/or <i>Blomia tropicalis</i>) AR, with or without comorbid CRSwNP. Key inclusion criteria were a clinician-confirmed diagnosis of SA and AR with a T2 signature according to specific guidelines<span><sup>7, 8</sup></span> and a CRSwNP diagnosis based on EPOS criteria.<span><sup>9</sup></span> Pregnant and breast-feeding women were excluded. The study was approved by the local Ethical Committee of our Institution and informed consent was signed by all participants.</p><p>Data from clinical records collected between January 2021 and July 2024 were retrospectively analyzed, with a total of 102 patients screened. Among them, 71 patients—40 females and 31 males, median age 48 years (IQR 21)—were confirmed as eligible for the study (Table S1). Outcome data from all participants were gathered and compared at two time points: before (T0) and 52-weeks post-commencement (T1) of monthly mepolizumab. Quantitative variables were presented as median and interquartile range (IQR), whereas qualitative variables were expressed as number of observations and percentage. Individual SNOT-22 item scores were summed, and a median domain score was derived. Pulmonary function test, including pre- and post-bronchodilator spirometry (Datospir 600<sup>®</sup>, Sibel S.A.U., Barcelona, Spain) and a validated asthma control test (ACT) were conducted in accordance with daily practice guid","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557306","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":"The expression of MUC5AC in patients with rhinosinusitis: A systematic review and meta-analysis","authors":"Yitao Li","doi":"10.1002/clt2.70003","DOIUrl":"10.1002/clt2.70003","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>To understand the connection between Muc5AC expression and the likelihood of rhinosinusitis, with the goal of providing insights into its prospective use as a biomarker.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases for studies up to November 2023 to conduct a literature review. After screening and quality assessment, eligible studies meeting the criteria were included. Muc5AC expression and rhinosinusitis association was analyzed by STATA 14.0.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Including weighted mean difference and 95% confidence interval, were reported. The meta-analysis included 16 studies with 1448 rhinosinusitis patients. MUC5AC expression was significantly up-regulated in both chronic rhinosinusitis with nasal polyps (CRSwNP; WMD: 0.52; 95% CI: 0.41–0.63) and chronic rhinosinusitis without nasal polyps (CRSsNP; WMD: 0.42; 95% CI: 0.28–0.56) patients compared to controls. IHC positive area analysis corroborated these findings, with elevated MUC5AC levels in CRSwNP (WMD: 25.61; 95% CI: 22.41–28.81) and CRSsNP (WMD: 39.74; 95% CI: 25.6–53.88) patients. Subgroup analysis based on tissue type (nasal tissue fluid and sinus mucosa) consistently supported the overall results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our meta-analysis robustly demonstrates a significant association between elevated MUC5AC expression and rhinosinusitis risk. This finding underscores the potential of MUC5AC as a molecular marker, providing valuable insights for future research and potential therapeutic interventions in rhinosinusitis management.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Systematic review registration</h3>\u0000 \u0000 <p>CRD42024518932.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557307","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}
Claudia Arasa, Niamh Hyland, Caroline Nilsson, Eva Sverremark-Ekström
{"title":"Pregnancy impacts allergy-related differences in the response to a type-1 stimulus, staphylococcal enterotoxin A","authors":"Claudia Arasa, Niamh Hyland, Caroline Nilsson, Eva Sverremark-Ekström","doi":"10.1002/clt2.70007","DOIUrl":"10.1002/clt2.70007","url":null,"abstract":"<p>To the Editor,</p><p><i>Staphylococcus (S</i>.<i>) aureus</i> is an intermittent or permanent skin colonizer in 90% of patients with airway diseases, and staphylococcal enterotoxin-IgE serum levels have been linked to both allergy and severe asthma.<span><sup>1, 2</sup></span> During pregnancy, immune adaptation is required to ensure fetal growth,<span><sup>3</sup></span> and type 2 responses are enhanced. These changes potentially worsen allergic conditions and increase the susceptibility to certain infections.<span><sup>4</sup></span></p><p>Here we investigate the immune response to Staphylococcal enterotoxin A (SEA), a strong inducer of type 1 responses, in individuals with Th2-skewing,<span><sup>5</sup></span> using peripheral blood mononuclear cells (PBMC) from allergic and non-allergic, pregnant and non-pregnant women<span><sup>6</sup></span> (Figure 1A). Staphylococcal enterotoxins cause polyclonal T cell activation crosslinking the MHC-II on antigen-presenting cells (APCs) to the T-cell receptor (TCR) on T-cells (Figure 1B), leading to a strong proinflammatory response, potentially increasing IgE-production or disrupting the maternal-fetal tolerance.</p><p>Allergic individuals exhibited reduced Tbet expression (Figure 1C), associated with Th1 response, and lower type 1 cytokine production (IFN-γ and TNF; Figure 1D). These differences were not observed during pregnancy (Figure S1A). GATA3 expression, linked to Th2 responses, was lower in allergic individuals regardless of their pregnancy status (Figure 1E), but there was no difference in type 2 cytokine secretion (IL-5 and IL-13; Figure S1B and Figure 1F). Type 3- and regulatory T cell markers (RORγt or FoxP3 expression and IL-17 and IL-10 secretion, respectively) did not differ in any of the groups (Figure S1C,D). Analyzing IFN-γ and TNF production in conventional T cells outside of pregnancy showed comparable IFN-γ levels between allergic and non-allergic individuals (Figure 1G). During pregnancy, IFN-γ production was significantly reduced in non-allergic individuals (Figure 1H) but not in allergic (Figure 1I). TNF production was lower in allergic individuals, but it increased during pregnancy (Figure S2A).</p><p>We have previously shown that the response to SEA by unconventional lymphocytes is delayed, and that their activation strongly contributes to the elicited cytokine storm<span><sup>7</sup></span> (Figure 2A). Therefore, we wanted to elucidate whether the allergy-related differences seen in conventional T cell activation correlated with variations in the unconventional lymphocyte compartment. All the analyzed cell types showed a consistent pattern, characterized by a significantly lower expression of IFN-γ (Figure 2B) and TNF (Figure S2B) in allergic women. Furthermore, analyzing the longitudinal response of unconventional lymphocytes to SEA in pregnant allergic women, we identified significantly higher production of both IFN-γ (Figure 2C) and TNF (Figure S2C) across all the st","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512600/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496243","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":"Response to comments on ‘Milk ladder versus early oral immunotherapy in infants with cow's milk protein allergy’","authors":"Chisato Inuo, Yurika Matsumoto","doi":"10.1002/clt2.70001","DOIUrl":"10.1002/clt2.70001","url":null,"abstract":"<p>Dear Editor,</p><p>We would like to thank the authors for their thoughtful and constructive comments on our publication, “Milk ladder versus early oral immunotherapy in infants with cow's milk protein allergy.” We appreciate their interest and engagement in this clinical discussion on the management of cow milk protein allergy (CMPA).</p><p>The use of dietary advancement therapies (DATs) such as milk and egg ladders is becoming widespread in the global allergy community. It is important to collect and share local data on these practices to expand our collective knowledge of the treatment of food allergies.</p><p>As the authors rightly pointed out, our study was conducted in a real-world clinical setting where, due to various practical constraints, we used parent-reported clinical histories and sensitization markers instead of the gold-standard Oral Food Challenge (OFC) for most patients. Data on patients who only had previous immediate allergic reactions due to the ingestion of cow milk protein is shown Table S1. The remaining patients had high levels of cow milk-specific IgE (>5 kU<sub>A</sub>/L), which exceeded 95% of the predicted value for diagnosing CMPA. We acknowledge that this is a limitation and agree that the absence of a challenge-proven allergy could have led to the inclusion of some children with asymptomatic sensitization or those with parent-reported symptoms without OFC. Nonetheless, we aimed to reflect the reality of clinical practice in which OFC is not always feasible or conducted in every case.</p><p>We also concur with the authors' insightful differentiation between the primary, secondary, and tertiary allergy prevention and the need to carefully classify patients undergoing milk introduction based on their clinical history and sensitization status. The suggestion that some patients in our study may have undergone the primary or secondary prevention is an important consideration. This underscores the complexity of managing food allergies in clinical settings where treatment protocols often overlap.</p><p>In agreement with the authors, we recognize that tolerance and reintroduction outcomes must be carefully labeled, particularly in the absence of prior confirmation of allergy through the OFC. We believe that further studies employing more rigorous diagnostic criteria will be crucial to refine treatment protocols and ensure that true allergic responses are addressed in our interventions.</p><p>Once again, we appreciate the authors' valuable feedback and our opportunity to further clarify and discuss the important aspects of CMPA management. We hope that our study contributes meaningfully to the ongoing advancement of DATs, such as Milk Ladder and Early Oral Immunotherapy, and we welcome further comments and discussions in this field.</p><p><b>Chisato Inuo</b>: Writing—original draft. <b>Yurika Matsumoto</b>: Writing—review and editing.</p>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11496043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496244","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":"Retrospective analysis of rapid drug desensitization with biologic agents: A single center experience","authors":"Döne Gülçin Unutmaz Erkaya, Makbule Seda Bayrak Durmaz, Begüm Görgülü Akın, Sevim Bavbek","doi":"10.1002/clt2.12397","DOIUrl":"10.1002/clt2.12397","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Following the increased use of biological agents, a subset of patients experiences hypersensitivity reaction (HSR). We reported our experience with rapid drug desensitization (RDD) to nine biologics (rituximab, infliximab, cetuximab, trastuzumab, pertuzumab, nivolumab, brentuximab, tocilizumab and filgrastim) and identified risk factors for breakthrough reactions (BTRs).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>This was a retrospective review (2013–2022) of patients with immediate HSRs to biological agents. Initial HSRs were classified as grade 1, 2, or 3 in their severity. Skin prick tests (SPT)/intradermal tests (IDT) were performed using implicated agents. The phenotypes of HSRs were defined as Type I, cytokine-release syndrome (CRS), mixed reactions (cytokine-release + type I) based on history, clinical presentations and skin tests with implicated biologicals. A 12-step RDD protocol was used.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study comprised 45 patients (F/M: 31/14, median age: 55 (range: 20–69)). Majority of the patients reacted at the first infusion (<i>n</i>: 29/45, 64.4%). The majority of initial HSRs were grade 3 (<i>n</i>: 24/45, 53.3%) and grade 2 (<i>n</i>: 21/45, 46.6%); none were grade 1. Initial reactions were presented as type I (<i>n</i>: 20/45, 44.4%), CRS (<i>n</i>: 12/45, 26.6%) and mixed (<i>n</i>: 13/45, 28.8%). A total of 258 RDDs were performed and 98.4% of them were completed successfully. BTRs occurred in 36/258 (13.9%) infusions of RDDs. There was no significant association between the BTRs and age, drug cycle, SPT and IDT positivity, gender, comorbidities, or atopy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In our experience, 98.4% of 258 RDDs to biologics were successfully completed; RDD was safe and effective for our population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11493553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459511","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}
Neera Chakrapani, Kyra Swiontek, Judith M. Hübschen, Jörg Fischer, Maria Ruiz-Castell, Francoise Codreanu-Morel, Farah Hannachi, Martine Morisset, Markus Ollert, Annette Kuehn, Claude P. Muller, Christiane Hilger
{"title":"Recurrent tick bites induce high IgG1 antibody responses to α-Gal in sensitized and non-sensitized forestry employees in Luxembourg","authors":"Neera Chakrapani, Kyra Swiontek, Judith M. Hübschen, Jörg Fischer, Maria Ruiz-Castell, Francoise Codreanu-Morel, Farah Hannachi, Martine Morisset, Markus Ollert, Annette Kuehn, Claude P. Muller, Christiane Hilger","doi":"10.1002/clt2.12396","DOIUrl":"https://doi.org/10.1002/clt2.12396","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The α-Gal syndrome (AGS) is characterized by the presence of specific IgE-antibodies to the carbohydrate galactose-α-1,3-galactose (α-Gal). Sensitization to α-Gal has been associated with tick bites and individuals exposed to ticks have an elevated risk of sensitization. The aim of this study was to analyze IgG and IgE antibody responses to α-Gal in a high-risk cohort of forestry employees (FE) in Luxembourg.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Questionnaires and serum samples of FE from Luxembourg (<i>n</i> = 219) were retrospectively analyzed. α-Gal specific IgE was quantified by ImmunoCAP, α-Gal specific IgG and subclasses IgG<sub>1–4</sub> were determined by ELISA. Additionally, sera from population-based controls (<i>n</i> = 150) and two groups of food-allergic patients, patients with AGS (<i>n</i> = 45) and fish-allergic patients (<i>n</i> = 22) were assessed for IgG antibody responses to α-Gal and cod extract.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-one percent of FE was sensitized to α-Gal (sIgE ≥ 0.1 kU<sub>A</sub>/L). Both sensitized and non-sensitized FE exhibited high levels of α-Gal specific IgG, IgG1 and IgG3 compared with controls, indicating a stimulation of IgG responses by recurrent tick bites, independent of the sensitization status. AGS patients had the highest levels of IgG1 and IgG2 antibodies, whereas the profile of fish-allergic patients was similar to the profile of the controls for which anti-α-Gal responses were dominated by IgG2 antibodies. α-Gal sIgG4 levels were either very low or undetectable in all groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study provides evidence for a continuous stimulation of α-Gal related immune responses by repeated tick bites, translating into highly elevated levels of IgG1 antibodies directed against α-Gal.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12396","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435630","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}
Anna Valerieva, Teresa Caballero, Markus Magerl, Joao P. Frade, Paul K. Audhya, Timothy Craig
{"title":"Advent of oral medications for the treatment of hereditary angioedema","authors":"Anna Valerieva, Teresa Caballero, Markus Magerl, Joao P. Frade, Paul K. Audhya, Timothy Craig","doi":"10.1002/clt2.12391","DOIUrl":"10.1002/clt2.12391","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable, debilitating episodes of submucosal and/or subcutaneous tissue swelling, which may be life-threatening depending on anatomic location. The two primary management strategies for HAE are ready access to effective on-demand treatment in all patients and the prevention of attacks (short-term prophylaxis [STP] and long-term prophylaxis [LTP]) in appropriate patients. All approved on-demand and most LTP medications require subcutaneous or intravenous administration. Injection-related challenges include trypanophobia (fear of needles), difficulty with self-administration, injection-site reactions (e.g., pain, erythema, bleeding, bruising), and anxiety—all contributing to poor compliance and administration delays. Oral HAE treatments may improve outcomes by reducing treatment barriers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>To review oral therapies, approved or in development, for on-demand treatment and/or prevention of HAE attacks.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>To provide a comprehensive review, data was obtained from publicly available resources through a targeted PubMed literature review and supplemented by information provided on company websites (search cutoff of May 31, 2024).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Berotralstat, an oral plasma kallikrein (PKa) inhibitor, is approved for LTP. Sebetralstat, another PKa inhibitor, is the investigational first oral on-demand HAE treatment to complete a phase 3 trial. Deucrictibant, an oral bradykinin B2 receptor antagonist, has completed phase 2 trials for on-demand therapy and LTP. Several other oral PKa inhibitors (ATN249, VE-4666, and VE-4062) are in early development for LTP.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Substantial advances have been made in the development of oral treatments for HAE. These treatments have the potential to improve and optimize clinical outcomes, satisfaction, and quality of life among patients with HAE.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11431061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342775","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}
Jianwei Wang, Yu Zhang, Ying Chen, Xinjun Xu, Yujuan Yang, Jiali Yin, Jing Guo, Pengyi Yu, Zhen Liu, Huifang Liu, Ting Zuo, Hongfei Zhao, Yan Hao, Bei Zhang, Xicheng Song
{"title":"Risk factors investigation for different outcomes between unilateral and bilateral chronic rhinosinusitis with nasal polyps patients","authors":"Jianwei Wang, Yu Zhang, Ying Chen, Xinjun Xu, Yujuan Yang, Jiali Yin, Jing Guo, Pengyi Yu, Zhen Liu, Huifang Liu, Ting Zuo, Hongfei Zhao, Yan Hao, Bei Zhang, Xicheng Song","doi":"10.1002/clt2.12395","DOIUrl":"https://doi.org/10.1002/clt2.12395","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Studies involving chronic rhinosinusitis with nasal polyps (CRSwNP) have mostly focused on bilateral cases, making unilateral CRSwNP inadequately recognized. This study examined the differences in clinical characteristics, outcomes, and risk factors for poor outcomes between unilateral and bilateral CRSwNP to facilitate a better assessment in the two groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Demographic information, tissue and blood cells, endoscopic scores, Lund-Mackay scores, recurrence rates, and disease control conditions were compared between 310 unilateral and 596 bilateral CRSwNP patients. Furthermore, the stepwise regression multivariate Cox proportional hazard models were performed to generate risk factors for poor outcomes in the two groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Bilateral cases exhibited higher rates of smoking, AR, and asthma comorbidities, along with higher numbers of tissue eosinophils and blood inflammatory cells when compared to unilateral patients. Endoscopic nasal polyp score, total computed tomography (CT) score (with scores for each sinus cavity), and adjusted CT scores were significantly higher in the bilateral group, except for a markedly higher adjusted maxillary score in the unilateral group. Furthermore, significantly higher proportions of bilateral patients experienced nasal polyp recurrence, uncontrolled status, and most disease control-related symptoms at follow-up. The primary risk factors for poor outcomes were asthma, tissue eosinophils, and total CT score in the bilateral group and blood basophils in the unilateral group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Bilateral CRSwNP patients experience worse disease severity and outcomes than their unilateral counterparts. Primarily, asthma, tissue eosinophils, and total CT score were risk factors for poor outcomes in bilateral CRSwNP patients, with blood basophils in unilateral cases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":10334,"journal":{"name":"Clinical and Translational Allergy","volume":null,"pages":null},"PeriodicalIF":4.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/clt2.12395","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320743","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}