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Search Results (395)

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14 pages, 926 KiB  
Article
The Role of TSLP and IL-1 β and Their Genetic Variants in the Pathogenesis of Single and Multiple Atopic Diseases in Children
by Hanna Sikorska-Szaflik, Anna Dębińska, Joanna Połomska, Anna Drabik-Chamerska and Barbara Sozańska
J. Clin. Med. 2025, 14(2), 598; https://doi.org/10.3390/jcm14020598 - 17 Jan 2025
Viewed by 368
Abstract
Allergic diseases commonly coexist, manifesting in a sequence described as the “allergic march”. Background/Objectives: This study aimed to evaluate TSLP’s and IL-1β’s potential as biomarkers in both single and multi-pediatric atopic diseases like atopic eczema, food allergy, and anaphylaxis and analyze specific SNPs [...] Read more.
Allergic diseases commonly coexist, manifesting in a sequence described as the “allergic march”. Background/Objectives: This study aimed to evaluate TSLP’s and IL-1β’s potential as biomarkers in both single and multi-pediatric atopic diseases like atopic eczema, food allergy, and anaphylaxis and analyze specific SNPs in the TSLP and IL-1β genes to determine their associations with their occurrence and severity. Methods: This analysis included 109 atopic children diagnosed with atopic dermatitis, food allergy, or anaphylaxis alongside a control group of 57 non-atopic children. Recruitment was facilitated through the use of a comprehensive questionnaire. For the study population, the allergen profile was characterized at the molecular level by measuring specific IgE to purified natural or recombinant allergens, assessing serum levels of circulating TSLP and IL-1β, and identifying single-nucleotide polymorphisms in TSLP (rs2289277) and IL-1β (rs16944 C-511T). Results: The serum levels of TSLP and IL-1β were elevated in the study groups compared to the control group, highlighting their significance in the pathogenesis of the studied diseases. Carrying a higher number of the risk allele [C] in the TSLP SNP rs2289277 is associated with the greatest likelihood of having multiple concurrent allergic conditions, with the highest risk observed in individuals with all three conditions—atopic dermatitis, food allergy, and anaphylaxis, simultaneously. Moreover, children carrying the risk allele had a twofold increased risk of polysensitization, which rose to sixfold in those with two copies of the risk allele. Although no significant variations in genotype frequencies were detected for IL-1β rs16944, significant associations were observed for TSLP rs2289277, particularly with conditions such as atopic dermatitis, food allergy, anaphylaxis, and combinations of these diseases. Conclusions: Further research is required to elucidate these pathways and their role in the development of allergic diseases. Full article
(This article belongs to the Special Issue New Clinical Advances in Pediatric Allergic Diseases)
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<p>Distribution of subgroup sizes in the study population.</p>
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<p>Serum concentrations of TSLP in the studied population. Statistical significance is indicated, with <span class="html-italic">p</span>-values displayed in exponential notation. The Kruskal–Wallis test was used for analysis, with a significance level set at <span class="html-italic">p</span> &lt; 0.05. All results were compared to the control group.</p>
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<p>Serum concentrations of IL-1β in the studied population. Statistical significance is indicated, with <span class="html-italic">p</span>-values displayed in exponential notation. The Kruskal–Wallis test was used for analysis, with a significance level set at <span class="html-italic">p</span> &lt; 0.05. All results were compared to the control group.</p>
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18 pages, 987 KiB  
Review
Edible Insects as an Alternative Source of Nutrients: Benefits, Risks, and the Future of Entomophagy in Europe—A Narrative Review
by Wojciech Michał Jankowski, Dominik Przychodniak, Weronika Gromek, Emilia Majsiak and Marcin Kurowski
Foods 2025, 14(2), 270; https://doi.org/10.3390/foods14020270 - 15 Jan 2025
Viewed by 968
Abstract
According to projections by the Food and Agriculture Organization of the United Nations, the global population will reach 9 billion by 2050. This raises concerns about the ability to feed such a population. In view of the above, it is necessary to search [...] Read more.
According to projections by the Food and Agriculture Organization of the United Nations, the global population will reach 9 billion by 2050. This raises concerns about the ability to feed such a population. In view of the above, it is necessary to search for alternative food sources. Edible insects are rich in complete protein, essential fatty acids, vitamins and micronutrients. Despite this, entomophagy is not common in Europe. In 2021, the European Union approved Acheta domesticus, Tenebrio molitor, Locusta migratoria, and Alphitobius diaperinus for consumption. However, their consumption may also be associated with certain hazards, e.g., food allergies. The purpose of this review is to present existing knowledge, discuss the possible dangers of consuming insects, and identify areas for further research. Studies in Asian populations indicate that edible insects may be responsible for 4.2–19.4% of food allergies and 18% of fatal food-induced anaphylaxis. There are also increasing reports from Europe of food allergies to edible insects. A thorough understanding of allergens, their properties, and the mechanisms of food allergies associated with edible insects’ consumption is essential for ensuring consumers’ safety. In the future, it would be worthwhile to investigate the effects of heat treatment on the allergenicity of insect proteins. Full article
(This article belongs to the Section Food Security and Sustainability)
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<p>Potential benefits of including edible insects in one’s diet.</p>
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<p>The percentage of people allergic to different combinations of two or three edible insects: <span class="html-italic">Locusta migratoria</span>, <span class="html-italic">Acheta domesticus</span> and <span class="html-italic">Tenebrio molitor</span>, as reported by Scala et al. [<a href="#B22-foods-14-00270" class="html-bibr">22</a>].</p>
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16 pages, 13773 KiB  
Article
Clinical and Immunological Features in Limpet (Patella sp.) Allergy in Subtropical Areas: A New Trigger for Food Anaphylaxis
by Elena Mederos-Luis, Tania Galán, María J. Martínez, Ruperto González-Pérez, Inmaculada Sánchez-Machín, Fernando Pineda and Paloma Poza-Guedes
Allergies 2025, 5(1), 2; https://doi.org/10.3390/allergies5010002 - 10 Jan 2025
Viewed by 384
Abstract
Seafood is a crucial source of nutrients, with global consumption steadily increasing. Among seafood-related allergies, shellfish are a significant cause of food allergy and anaphylaxis worldwide, affecting approximately 0.5–2.5% of the general population. While the majority of existing research has focused on crustaceans, [...] Read more.
Seafood is a crucial source of nutrients, with global consumption steadily increasing. Among seafood-related allergies, shellfish are a significant cause of food allergy and anaphylaxis worldwide, affecting approximately 0.5–2.5% of the general population. While the majority of existing research has focused on crustaceans, allergic reactions to mollusks, including their clinical characteristics, remain poorly understood. In the Canary Islands, limpets (a type of marine gastropod) are widely consumed as part of the traditional cuisine. Despite isolated reports of limpet allergy, no large-scale studies or comprehensive clinical analyses have been published on this topic. A cohort of patients sensitized to limpets was analyzed: 66 patients were monosensitized to limpets (Group A), while 64 patients demonstrated additional sensitization to other shellfish (Group B). Limpet ingestion was associated with delayed and severe symptoms, including anaphylaxis and severe asthma. Notably, only 11.5% of patients in Group A tested positive for shellfish allergens using ALEX testing compared to 67.9% in Group B. The identification of protein bands in the 25–40 and 50–200 kDa molecular weight ranges in monosensitized patients provides a novel finding that differentiates this study from prior research. Our study represents the largest reported series of patients with documented limpet allergy to date. Full article
(This article belongs to the Section Food Allergy)
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<p>Summary of respiratory symptoms following ingestion of limpets in patients without previous diagnoses of asthma. SBE: severe bronchospasm; others: urticaria, angioedema, rinoconjuncthivitis, etc.</p>
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<p>SDS-PAGE (<b>1</b>) and IgE Western blot (<b>2</b>) under reducing conditions with the sera pool of all patients from Group A and Group B relative to limpet extracts and with the individual sera (<b>3</b>) of 16 random patients from Group A and Group B relative to allergens of raw and cooked black limpets (<span class="html-italic">Patella crenata</span>), raw and cooked white limpets (<span class="html-italic">Patella aspera</span>), and cooked shrimp extract.</p>
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27 pages, 3389 KiB  
Systematic Review
Post-Vaccination Anaphylaxis in Adults: A Systematic Review and Meta-Analysis
by Flavia Pennisi, Anna Carole D’Amelio, Rita Cuciniello, Stefania Borlini, Luigi Mirzaian, Giovanni Emanuele Ricciardi, Massimo Minerva, Vincenza Gianfredi and Carlo Signorelli
Vaccines 2025, 13(1), 37; https://doi.org/10.3390/vaccines13010037 - 4 Jan 2025
Viewed by 710
Abstract
Background/Objectives: Vaccines have been recognized as one of the most effective public health interventions. However, vaccine-associated anaphylaxis, although rare, is a serious adverse reaction. The incidence of anaphylaxis related to non-COVID-19 vaccines in adults remains underreported. This systematic review and meta-analysis aim to [...] Read more.
Background/Objectives: Vaccines have been recognized as one of the most effective public health interventions. However, vaccine-associated anaphylaxis, although rare, is a serious adverse reaction. The incidence of anaphylaxis related to non-COVID-19 vaccines in adults remains underreported. This systematic review and meta-analysis aim to estimate the incidence of post-vaccination anaphylaxis across various vaccines in adults. Methods: A comprehensive literature search of PubMed, Embase, Scopus, and Web of Science identified studies on anaphylaxis following vaccination in adults (≥18 years), excluding COVID-19 vaccines. PRISMA 2020 guidelines were followed. The protocol was registered in PROSPERO in advance (ID CRD42024566928). Random-effects and fixed-effects models were used to pool data and estimate the logit proportion, with the logit-transformed proportion serving as the effect size, thereby allowing for the calculation of event rates. Results: A total of 37 studies were included in the systematic review, with 22 studies contributing to the meta-analysis, representing a combined population of 206,855,261 participants. Most studies focused on influenza vaccines (n = 15). Across all studies, 262 anaphylactic cases were reported, with 153 cases related to influenza vaccines, followed by herpes zoster virus vaccines (38 cases) and yellow fever vaccines (29 cases). Td/Tdap vaccine had the lowest rate (0.0001 per 100,000 participants). The overall random-effects model yielded a logit proportion of −10.45 (95% CI: −12.09 to −8.82, p < 0.001), corresponding to an event rate of 2.91 events per 100,000 subjects (95% CI: 0.56 to 14.73). Sensitivity analysis showed a higher incidence for influenza, hepatitis vaccines, and in vulnerable populations. Conclusions: Anaphylaxis following vaccination in adults is rare but varies by vaccine type. Strengthened monitoring and preparedness are essential, especially in non-medical settings, to ensure a rapid response to anaphylaxis and maintain public confidence in vaccination programs. Full article
(This article belongs to the Section Vaccine Efficacy and Safety)
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<p>PRISMA flow diagram of study search, screen, assessment, and extraction.</p>
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<p>Annual publication distribution of included studies.</p>
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<p>Geographical distribution of studies conducted by country.</p>
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<p>(<b>a</b>) Forest plot and (<b>b</b>) funnel plot of the random-effects model assessing the logit proportion among all vaccine types. In the forest plot, the effect sizes of individual studies are represented in blue, while the overall effect size is shown in green.</p>
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<p>Forest plot of the random-effects model assessing the logit proportion among each vaccine type. RZV = recombinant zoster vaccine. Td/Tdap = tetanus and diphtheria or tetanus toxoid, reduced diphtheria toxoid, acellular pertussis. In the forest plot, the effect sizes of individual studies are represented in blue, the overall effect size for each vaccine type is shown in red, and the overall effect size for all vaccine types combined is displayed in green.</p>
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<p>Forest plot of the fixed-effects model assessing the logit proportion among each vaccine type. RZV = recombinant zoster vaccine. Td/Tdap = tetanus and diphtheria or tetanus toxoid, reduced diphtheria toxoid, acellular pertussis. In the forest plot, the effect sizes of individual studies are represented in blue, the overall effect size for each vaccine type is shown in red, and the overall effect size for all vaccine types combined is displayed in green.</p>
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<p>Forest plot of the random-effects model assessing the logit proportion among vulnerable populations (individuals with pre-existing allergies or chronic conditions). In the forest plot, the effect sizes of individual studies are represented in blue, while the overall effect size is shown in green.</p>
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22 pages, 3048 KiB  
Review
Regulating Immune Responses Induced by PEGylated Messenger RNA–Lipid Nanoparticle Vaccine
by Hyein Jo, Jaewhoon Jeoung, Wonho Kim and Dooil Jeoung
Vaccines 2025, 13(1), 14; https://doi.org/10.3390/vaccines13010014 - 27 Dec 2024
Viewed by 539
Abstract
Messenger RNA (mRNA)-based therapeutics have shown remarkable progress in the treatment and prevention of diseases. Lipid nanoparticles (LNPs) have shown great successes in delivering mRNAs. After an mRNA-LNP vaccine enters a cell via an endosome, mRNA is translated into an antigen, which can [...] Read more.
Messenger RNA (mRNA)-based therapeutics have shown remarkable progress in the treatment and prevention of diseases. Lipid nanoparticles (LNPs) have shown great successes in delivering mRNAs. After an mRNA-LNP vaccine enters a cell via an endosome, mRNA is translated into an antigen, which can activate adaptive immunity. mRNAs can bind to various pattern recognition receptors (PRRs), including toll-like receptors (TLRs), and increase the production of inflammatory cytokines. This review summarizes mechanisms of innate immunity induced by mRNAs. Polyethylene glycol (PEG) has been employed as a component of the mRNA-LNP vaccine. PEGylated nanoparticles display enhanced stability by preventing aggregation of particles. However, PEGylation can cause adverse reactions, including blood clearance (ABC) of nanoparticles via complement activation and anaphylaxis. Mechanisms of PEG-induced ABC phenomenon and anaphylaxis are presented and discussed. There have been studies aimed at reducing immune responses associated with PEG to make safe and effective vaccines. Effects of modifying or replacing PEG in reducing immune responses associated with PEGylated nanoparticles are also discussed. Modifying mRNA can induce immune tolerance, which can prevent hypersensitivity reactions induced by PEGylated mRNA-LNP vaccines. Current progress of immune tolerance induction in association with mRNA-LNP is also summarized. This review might be helpful for developing safe and effective PEGylated mRNA-LNP vaccines. Full article
(This article belongs to the Special Issue Advance in Nanoparticles as Vaccine Adjuvants)
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<p>Immune responses induced by mRNA vaccines. mRNA-LNP vaccine is endocytosed by antigen presenting cells. Following endosomal escape, mRNAs are then translated into corresponding proteins. Proteins undergo proteasomal degradation. Peptides are then presented on MHC-I to induce activation of CD8<sup>+</sup> T cells. Activated CD8<sup>+</sup> T cells can secrete IFNγ and TNF-α. Activated CD8<sup>+</sup> T cells can kill tumor cells by granzyme B (GzmB). Secreted proteins are recognized and engulfed by antigen presenting cells such as B cells. Antigenic peptides are presented on the MHC-II of B cells to induce activation of CD4<sup>+</sup> T cells. Activated CD4<sup>+</sup> T cells, such as TH2 cells and TFH cells, can activate B cells to induce production of antigen-specific antibodies. Arrows denote the direction of reaction. TFH denotes follicular T helper cells. IVT denotes in vitro transcription.</p>
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<p>Innate immunity and translational inhibition induced by mRNA. (<b>A</b>) Endosomal TLR (TLR3, 7, or 8) can bind to ssRNA or dsRNA. Endosomal TLR7/8 can increase the production of type I IFNs and various proinflammatory cytokines including IL-6, CCL2, and CXCL10 by activating MYD88-NF-kB signaling. DsRNA produced during IVT can activate PKR or OAS pathway, resulting in degradation of mRNA. Endosomal TLR3 can bind to dsRNA and activate TRIF pathway. RLRs and MDA5 can bind to cytosolic RNAs and increase production of proinflammatory cytokines by activating IRF3 and N-kB. (<b>B</b>) DsRNA can bind to PKR and OAS. PKR can suppress mRNA translation by inducing phosphorylation of eIF2. OAS can activate RNase L, which in turn can induce translational arrest. Hollow arrows denote the direction of reaction. IRAK, interleukin-1-receptor-associated kinase; MAVS, mitochondrial antiviral-signaling protein; TAB, Mitogen-activated <span class="html-italic">protein</span> kinase kinase kinase 7-interacting <span class="html-italic">protein</span> 1; TAK, mitogen-activated <span class="html-italic">protein</span> kinase kinase kinase 7; TRAF6, tumor necrosis factor receptor-associated factor 6; TRAM, translocating- chain-associated membrane protein; ZAK, mixed lineage kinase. Hollow arrows denote the direction of reaction. T bars denote inhibition of reaction.</p>
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<p>PEG induces complement activation-associated anaphylaxis and ABC phenomenon. PEGylated mRNA-LNP vaccine induces cross linking of B cell receptors. B cells are then differentiated into plasma cells. Plasma cells produce anti-PEG antibodies. Anti-PEG IgE activates immune cells such as mast cells and basophils, resulting in anaphylaxis through Fcε receptor in a complement-independent manner. PEG-anti-PEG-IgM complex can activate complement via classical pathway. Activation of complement produces anaphylatoxins such as C3a and C5a. These anaphylatoxins can stimulate mast cells to release various mediators and induce degranulation of mast cells. Anaphylatoxins can also induce immune cells to release PAF. PAF can bind to mast cells to cause degranulation of mast cells. PEG-mRNA-LNP vaccine can induce the production of anti-PEG IgM, which in turn can bind PEG-LNP. This binding can induce complement activation to produce complement fragments such as C3b and C5b. C3 can activate C5 convertase to produce C5a and C5b. These fragments can bind to complement receptors (CR3 and CR4) to induce ABC phenomenon by macrophages. Arrows denote the direction of reaction. ↓ denotes decreased expression/activity and ↑ denotes increased expression/activity. LTR, leukotriene receptor; TxA2, thromboxane A2; PGE, poly glutamic acid ethylene oxide.</p>
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<p>Induction of immune tolerance by mRNA-LNP. After endocytosis of modified PEG-mRNA-LNP vaccine by APC, mRNA undergoes endosomal escape. mRNA is then released and translated into antigen. Antigenic epitopes can be presented on MHC-II and bind to TCR on CD4<sup>+</sup> T cells. CD4<sup>+</sup> T cells are then differentiated into FoxP3<sup>+</sup> Treg cells. Treg cells can secrete immune suppressive cytokines such as IL-10 and TGF-β. These Treg cells can induce immune tolerance. This tolerogenic effect is accompanied by decreased expression TH2 cytokines and IgE. CTLA-4, cytotoxic T-lymphocyte antigen 4; IVT, in vitro transcription; LAG3, lymphocyte activation gene-3; PD-1, programmed death-1; RA, rheumatoid. Arrows and hollow arrows denote the direction of reaction. T bars denote inhibition of reaction. ↑ denotes increased expression/activity.</p>
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10 pages, 427 KiB  
Article
Successful Desensitization to Irinotecan in a Patient with Metastatic Esophageal Squamous Cell Carcinoma and a History of Anaphylaxis in Response to Irinotecan—Case Report and Literature Review
by Selda Ali, Denisa-Mihaela Nedelcu, Radu Serescu and Roxana Silvia Bumbăcea
J. Clin. Med. 2024, 13(24), 7824; https://doi.org/10.3390/jcm13247824 - 21 Dec 2024
Viewed by 531
Abstract
Background: Irinotecan is a topoisomerase I inhibitor used for the treatment of various cancers, such as gastrointestinal, pancreatic, pulmonary, ovarian, and cervical cancers. Among chemotherapy agents, it represents a rare trigger of drug hypersensitivity reactions, with few cases being reported until today. [...] Read more.
Background: Irinotecan is a topoisomerase I inhibitor used for the treatment of various cancers, such as gastrointestinal, pancreatic, pulmonary, ovarian, and cervical cancers. Among chemotherapy agents, it represents a rare trigger of drug hypersensitivity reactions, with few cases being reported until today. Methods: We present the case of a patient with metastatic esophageal cancer and a history of irinotecan-induced grade IV (WAO classification) anaphylaxis. An IgE-mediated reaction was confirmed in our case, as evidenced by a positive intradermal skin test result, and we carried out a successful desensitization protocol, given irinotecan’s indispensability in the treatment regimen. Our case underscores the fact that in such situations where the culprit drug is also the only therapeutic option available for such a patient, implementing a desensitization protocol may represent the only viable approach to ensure safe and successful dosing. Results: A comprehensive review of the literature was also conducted to assess previously reported irinotecan-induced hypersensitivity reactions, the utility of skin tests in identifying sensitisation to irinotecan, and the existing desensitization protocols. We found a total of seventeen cases of hypersensitivity reactions to irinotecan in the literature, out of which four provided the skin test results obtained and six performed desensitization protocols for irinotecan. Conclusions: Our literature review highlights that skin testing and desensitization protocols can provide suitable solutions for managing hypersensitivity reactions to irinotecan. Full article
(This article belongs to the Section Dermatology)
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<p>Positive response to <span class="html-italic">irinotecan</span> intradermal test, 2 mg/mL concentration.</p>
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14 pages, 1209 KiB  
Article
Exploring Beekeepers’ Experiences and Perceptions of Anaphylaxis Risks: A Qualitative Study to Inform Targeted Health Education Programs
by Tea Močnik, Sabina Ličen, Mihaela Zidarn and Mirko Prosen
Healthcare 2024, 12(24), 2569; https://doi.org/10.3390/healthcare12242569 - 20 Dec 2024
Viewed by 723
Abstract
Background: Beekeeping plays crucial natural and economic roles but also poses health risks, as bee stings can cause severe allergic reactions like anaphylaxis, a potentially life-threatening condition that requires timely intervention. Understanding symptoms and the proper use of adrenaline autoinjectors is essential to [...] Read more.
Background: Beekeeping plays crucial natural and economic roles but also poses health risks, as bee stings can cause severe allergic reactions like anaphylaxis, a potentially life-threatening condition that requires timely intervention. Understanding symptoms and the proper use of adrenaline autoinjectors is essential to minimize risks. This study aimed to assess the need for education on anaphylaxis and to develop a health education program to enhance beekeepers’ preparedness and safety. Methods: A qualitative descriptive interpretative method was employed. Two focus groups were conducted, one with eight health care professionals specializing in allergy and clinical immunology and the other with six active beekeepers. The data were analyzed via content analysis using QDA Miner® Lite v3.0.5 software. Results: The analysis structure comprises five thematic areas: (1) the management of anaphylaxis; (2) the prevention of anaphylaxis; (3) health education approaches; (4) systemic approaches in prevention; and (5) adrenaline autoinjectors. The results highlight key challenges, including the need for better strategies to manage anaphylaxis, improve prevention, and provide practical educational programs for beekeepers. There is also a need for better collaboration between health care professionals and beekeepers, as well as improved access to and knowledge of adrenaline autoinjectors. Conclusions: Targeted education for beekeepers on recognizing anaphylaxis symptoms and using adrenaline autoinjectors is essential for timely intervention and preventing severe outcomes. Given their exposure to bee stings, beekeepers require proper training and regular practice to improve preparedness and safety. This research underscores the need for a comprehensive educational program to reduce anaphylaxis risk and enhance safety in beekeeping. Full article
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<p>Diagram of key themes in anaphylaxis prevention and management among beekeepers: findings from focus group analysis.</p>
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<p>Word cloud of the most frequently used words in the focus groups.</p>
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11 pages, 1786 KiB  
Article
Molecular Profiles of Sensitization to Non-Specific Lipid Transfer Proteins in Lithuania: Single Center Experience
by Sandra Sakalauskaite, Ligita Pilkyte, Edita Gasiuniene and Brigita Gradauskiene
Int. J. Mol. Sci. 2024, 25(24), 13535; https://doi.org/10.3390/ijms252413535 - 18 Dec 2024
Viewed by 662
Abstract
Non-specific Lipid Transfer proteins (nsLTPs) are relevant allergens of several pollens and plant foods. Sensitization to nsLTPs is not typical in our region. Still, it has become an increasingly common cause of IgE-mediated food allergies and food-induced anaphylaxis in Northern Europe in recent [...] Read more.
Non-specific Lipid Transfer proteins (nsLTPs) are relevant allergens of several pollens and plant foods. Sensitization to nsLTPs is not typical in our region. Still, it has become an increasingly common cause of IgE-mediated food allergies and food-induced anaphylaxis in Northern Europe in recent decades. No in-depth studies describe the prevalence of sensitization of molecular components to nsLTPs in Lithuania. This study aimed to determine the sensitization profile of atopic patients at the Immunology and Allergy Department of Kauno Klinikos to the components of nsLTPs, using molecular allergen component analysis. Sixty Lithuanian adults with symptoms of allergic rhinitis and/or allergic asthma and/or food allergies were included into the study. Specific immunoglobulin E (IgE) levels were measured using two in vitro techniques: allergen extract and molecular component analysis. Results showed that 25% of subjects were sensitized to nsLTP-containing allergen sources, mostly to Zea m 14, Mal d 3, Vit v 1, and Art v 3. The median amount of total IgE was higher in nsLTP-sensitized patients than in nsLTP-nonsensitized patients. Based on Cohen’s Kappa and McNemar tests, the results of allergen extract and component analysis tests do not always agree, especially when we determine the sensitization to allergen sources containing nsLTPs. Molecular allergen component analysis could be the first choice in determining detailed sensitization to nsLTPs in patients who experienced anaphylaxis of unknown origin. Full article
(This article belongs to the Special Issue Molecular Therapeutic Strategies in Allergic Diseases)
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<p>The prevalence of sensitization of the whole allergen source (<b>a</b>) and their separate molecular components (<b>b</b>) in studied group. Cases of sensitization indicated in both parts—%.</p>
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<p>The prevalence of sensitization to nsLTP-containing allergen sources (<b>a</b>) and to different nsLTPs (<b>b</b>). Data presented as percentage of the whole group (<b>a</b>) and percentage of nsLTP-sensitized subjects (<b>b</b>).</p>
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<p>The amount of total IgE in nsLTP-sensitized subjects or without sensitization to nsLTPs (minimum data value, lower quartile value, median value, upper quartile value, maximum data value, outliers).</p>
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<p>The sensitization profiles to nsLTP components. Different patients indicated as (<b>A</b>–<b>O</b>). The concentration of sIgE up to 5 kUA/L (<b>A</b>–<b>I</b>), up to 15 kUA/L (<b>J</b>–<b>L</b>), and up to 50 (<b>M</b>–<b>O</b>).</p>
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15 pages, 752 KiB  
Review
Tree Nut Allergy in Children—What Do We Know? —A Review
by Anna Chudoba, Agata Żebrowska and Adam J. Sybilski
Nutrients 2024, 16(23), 3978; https://doi.org/10.3390/nu16233978 - 21 Nov 2024
Viewed by 1045
Abstract
Food allergy represents a significant public health concern, with its prevalence increasing in recent decades. Tree nuts are among major allergenic foods, and allergies to them are frequently linked to severe and potentially life-threatening reactions. Data on the prevalence and natural history of [...] Read more.
Food allergy represents a significant public health concern, with its prevalence increasing in recent decades. Tree nuts are among major allergenic foods, and allergies to them are frequently linked to severe and potentially life-threatening reactions. Data on the prevalence and natural history of tree nut allergy are limited. Primary nut allergy typically presents with rapid-onset IgE-mediated symptoms. Diagnosis can be confirmed by demonstrating a positive skin prick test (SPT), specific IgE (sIgE), or through an oral food challenge. Component-resolved diagnostics (CRD) can identify those with a high risk of anaphylaxis. The main management strategy involves avoiding the culprit allergen and treating symptoms after accidental exposure. New therapeutic options, such as sublingual immunotherapy, oral food immunotherapy, with or without omalizumab, and other monoclonal antibodies, are being investigated to modify tree nut allergy. Tree nut allergy is a lifelong disease with a low likelihood of resolution. The aim of this paper is to present the current data on the prevalence, diagnosis, natural history, and management options for tree nut allergy. Full article
(This article belongs to the Section Pediatric Nutrition)
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<p>Diagnostic algorithm for tree nut allergy according to BSACI [<a href="#B5-nutrients-16-03978" class="html-bibr">5</a>] (modified by the author) [<a href="#B5-nutrients-16-03978" class="html-bibr">5</a>].</p>
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12 pages, 1417 KiB  
Article
Use of Granulocyte Transfusions in the Management of Severe Infections Among Children with Neutropenia
by Gabriela Mielecka-Jarmocik, Katarzyna Szymbor, Walentyna Balwierz, Szymon Skoczeń, Marta Leń, Kinga Kania and Katarzyna Pawińska-Wąsikowska
J. Pers. Med. 2024, 14(11), 1107; https://doi.org/10.3390/jpm14111107 - 15 Nov 2024
Viewed by 809
Abstract
Background/Objectives: Infections remain the leading cause of mortality among neutropenic patients with haematologic malignancies, making effective infection management crucial. Achieving a sufficient neutrophil count is essential for the elimination of pathogens. Granulocyte concentrate (GC) can be a treatment option for neutropenic patients with [...] Read more.
Background/Objectives: Infections remain the leading cause of mortality among neutropenic patients with haematologic malignancies, making effective infection management crucial. Achieving a sufficient neutrophil count is essential for the elimination of pathogens. Granulocyte concentrate (GC) can be a treatment option for neutropenic patients with severe infections. This study aimed to evaluate the efficacy, safety, and impact on survival of GC transfusions in neutropenic children with severe infections treated over the past 13 years in a single centre. Methods: The retrospective study analysed clinical data from 60 children (median age 9.5 years) who received GC transfusions at our centre. Granulocytes were collected by apheresis from donors stimulated with granulocyte colony-stimulating factor. The majority of the patients (70%) were diagnosed with acute leukaemia. The main indications for GC were severe pneumonia (45%) and bacterial sepsis (38.33%). Results: The patients received 1 to 29 GC transfusions for 1 to 70 days, with a median time of administration of 3 days. Neutrophil counts increased to >1000/µL within a median of 5 days. GCs were well tolerated by most patients. One patient presented symptoms of anaphylaxis, the other acute lung injury related to transfusions, and alloimmunisation was reported in one patient. Of the patients analysed, 78.33% survived the infection that justified GC administration. We did not observe significant differences in survival depending on the aetiology of the infection. Conclusions: Based on our research, GC appears to be a beneficiary for neutropenic children with severe infections and reduces infection mortality rates. However, further well-designed randomised trials are needed to define its role in this setting. Full article
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<p>Infectious indications for GC treatment.</p>
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<p>The correlation between the patient’s age and the received number of granulocytes per kilogramme of body weight per day. Continuous red line—the graphical representation of negative correlation; dashed orange lines—the 95% confidence intervals for the correlation line; orange dots—the single records; turquoise solid line - the border above which the number of granulocytes in GC was sufficient.</p>
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<p>TRALI after GC transfusion.</p>
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10 pages, 2767 KiB  
Article
Uricase-Expressing Engineered Macrophages Alleviate Murine Hyperuricemia
by Yu-Zhong Feng, Hao Cheng, Guo-Qing Xiong, Jia-Zhen Cui, Zhi-Li Chen, Yuan-Yuan Lu, Zhi-Xin Meng, Chen Zhu, Hao-Long Dong, Xiang-Hua Xiong, Gang Liu, Qing-Yang Wang and Hui-Peng Chen
Biomedicines 2024, 12(11), 2602; https://doi.org/10.3390/biomedicines12112602 - 14 Nov 2024
Viewed by 961
Abstract
Background: Uricase, or urate oxidase (Uox) is a key enzyme in uric acid (UA) metabolism and has been applied in clinical treatment of human hyperuricemia (HUA). However, the current clinically applied uricases, despite their potent urate-lowering capacity, tend to form anti-drug antibodies [...] Read more.
Background: Uricase, or urate oxidase (Uox) is a key enzyme in uric acid (UA) metabolism and has been applied in clinical treatment of human hyperuricemia (HUA). However, the current clinically applied uricases, despite their potent urate-lowering capacity, tend to form anti-drug antibodies because of their immunogenicity, leading to increased risk of anaphylaxis, faster drug clearance and reduced or even complete loss of therapeutic effect, limiting their clinical application. In this study, we constructed engineered macrophages that stably expressed uricase, which might serve as a promising alternative to the direct injection of uricases. Materials and Methods: Engineered macrophages RAW264.7 cells were injected intravenously to treat hyperuricemic KM mice. Serum uric acid and bio-indicators for renal and hepatic functions were detected by an automatic biochemical analyzer; inflammatory cytokines were determined by ELISA; the livers and kidneys of the mice were sectioned for histological examination. Results: The uricase-expressing macrophages reduced UA levels from 300 ± 1.5 μmol/L to 101 ± 8.3 μmol/L in vitro. And in an HUA mouse model established by gavage with yeast extract, intravenous injection of the engineered macrophages could reduce the serum uric acid (sUA) of mice to normal level on the 14th day of modeling, with a decrease of 48.6%, and the urate-lowering effect was comparable to that of the first-line clinical drug allopurinol. In terms of safety, engineered macrophages did not cause liver or kidney dysfunction in mice, nor did they induce systemic immune response. Conclusions: Using macrophages as a chassis to deliver uricase might be a new, safe and effective strategy for the treatment and control of hyperuricemia. Full article
(This article belongs to the Section Cell Biology and Pathology)
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<p><span class="html-italic">mus</span>-Uri expression in the engineered macrophage RAW264.7. (<b>A</b>) Positive rate after lentiviral transfection, detected by flow cytometry; (<b>B</b>) uricase relative expression determined by qPCR; (<b>C</b>) <span class="html-italic">mus</span>-Uri protein expression confirmed by Western blotting.</p>
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<p>Engineered macrophage reduces UA level in vitro. Comparison was performed between RAW-mus Uri and RAW-Ctrl groups at each time point. (n = 10, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>(<b>A</b>) Rate of EGFP-positive RAW264.7 after cytometry sorting; P1 represents all viable cells, while P2 represents EGFP-positive cells. (<b>B</b>) Uric acid levels in each group 0, 7, and 14 days after intervention. The levels between HUA + RAW-Ctrl and HUA + RAW-Uri were compared. (n = 10, *** <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Safety evaluation of engineered macrophage RAW-<span class="html-italic">mus</span>-Uri. (<b>A</b>) Hepatic function indicators AST, ALT, TBIL and DBIL and renal function indicators urea and crea collected from serum are assessed. (n = 10, *** <span class="html-italic">p</span> &lt; 0.001) (<b>B</b>,<b>C</b>) H&amp;E staining and histological examination of liver (<b>B</b>) and kidney (<b>C</b>) in each group.</p>
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15 pages, 3249 KiB  
Article
Antimicrobial Peptide Pro10-1D Exhibits Anti-Allergic Activity: A Promising Therapeutic Candidate
by Min Yeong Choi, Min Geun Jo, Keun Young Min, Byeongkwon Kim, Yangmee Kim and Wahn Soo Choi
Int. J. Mol. Sci. 2024, 25(22), 12138; https://doi.org/10.3390/ijms252212138 - 12 Nov 2024
Viewed by 833
Abstract
Although antimicrobial peptides (AMPs) exhibit a range of biological functions, reports on AMPs with therapeutic effects in allergic disorders are limited. In this study, we investigated the anti-allergic effects of Pro10-1D, a 10-meric AMP derived from insect defensin protaetiamycine. Our findings demonstrate that [...] Read more.
Although antimicrobial peptides (AMPs) exhibit a range of biological functions, reports on AMPs with therapeutic effects in allergic disorders are limited. In this study, we investigated the anti-allergic effects of Pro10-1D, a 10-meric AMP derived from insect defensin protaetiamycine. Our findings demonstrate that Pro10-1D effectively inhibits antigen-induced degranulation of mast cells (MCs) with IC50 values of approximately 11.6 μM for RBL-2H3 cells and 2.7 μM for bone marrow-derived MCs. Furthermore, Pro10-1D suppressed the secretion of cytokines with IC50 values of approximately 2.8 μM for IL-4 and approximately 8.6 μM for TNF-α. Mechanistically, Pro10-1D inhibited the Syk-LAT-PLCγ1 signaling pathway in MCs and decreased the activation of mitogen-activated protein kinases (MAPKs). Pro10-1D demonstrated a dose-dependent reduction in IgE-mediated passive cutaneous anaphylaxis in mice with an ED50 value of approximately 7.6 mg/kg. Further investigation revealed that Pro10-1D significantly reduced the activity of key kinases Fyn and Lyn, which are critical in the initial phase of the FcεRI-mediated signaling pathway, with IC50 values of approximately 22.6 μM for Fyn and approximately 1.5 μM for Lyn. Collectively, these findings suggest that Pro10-1D represents a novel therapeutic candidate for the treatment of IgE-mediated allergic disorders by targeting the Lyn/Fyn Src family kinases in MCs. Full article
(This article belongs to the Collection Feature Papers in Molecular Pharmacology)
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<p>Pro10-1D inhibits IgE–Ag-induced degranulation in MCs. (<b>A</b>) RBL-2H3 cells and BMMCs were first sensitized with DNP-specific IgE and then treated with Pro10-1D or PP2 for 30 min, followed by the stimulation with DNP-HSA for 15 min. (<b>B</b>) IgE-sensitized RBL-2H3 cells were incubated with or without Pro10-1D for 30 min and then washed three times, followed by the stimulation with the antigen for 15 min. (<b>C</b>) The effects of Pro10-1D on cell viability were evaluated by incubating both RBL-2H3 cells and BMMCs with Pro10-1D for 4 h and measuring the absorbance at 450 nm using the CCK-8 kit. (<b>A</b>,<b>B</b>) The extent of degranulation from the MCs was determined by measuring the ratio of β-hexosaminidase activity released outside the cells to the total β-hexosaminidase activity. The data are presented as the mean ± SEM from three independent experiments, each performed in triplicate. Statistical significance is indicated by an asterisk; * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01. PP2 is a general Src family kinase inhibitor.</p>
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<p>Pro10-1D suppresses the activation of FcεRI-mediated signaling proteins in MCs. (<b>A</b>) RBL-2H3 cells (8.0 × 10<sup>5</sup> cells/well) or (<b>B</b>) BMMCs (2.0 × 10<sup>6</sup> cells/well) were sensitized with DNP-specific IgE and then treated with Pro10-1D for 30 min, followed by the stimulation with 25 ng/mL and 50 ng/mL DNP-HSA, respectively, for 15 min. Western blotting was performed as described in the <a href="#sec4-ijms-25-12138" class="html-sec">Section 4</a> “Materials and Methods”. The images shown are representative results from three independent experiments.</p>
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<p>Pro10-1D decreases the release of inflammatory cytokines in BMMCs by antigen stimulation. (<b>A</b>,<b>B</b>) BMMCs (2.0 × 10<sup>6</sup> cells/well) sensitized with DNP-specific IgE were treated with Pro10-1D for 30 min and then stimulated with 50 ng/mL DNP-HSA for 3 h. After incubation, the concentrations of IL-4 and TNF-α released into the culture media were subsequently measured by ELISA. The data are represented as the mean ± SEM from three independent experiments. Statistical significance is indicated by an asterisk; ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Pro10-1D diminishes the IgE-mediated passive cutaneous anaphylaxis (PCA) reaction. Mice were intradermally injected with DNP-specific IgE (50 ng) in their ear. After 12 h, they were intraperitoneally injected with Pro10-1D at concentrations of 5, 10, and 20 mg/kg, with cetirizine (20 mg/kg) serving as a reference drug. One hour later, DNP-HSA with Evans blue was administered by intravenous injection. The images in (<b>A</b>) depict representative ear images for each group. (<b>B</b>) Evans blue dye extravasation was quantified by absorption at 620 nm. (<b>C</b>) The ears of the mice from the experiment depicted in (<b>A</b>) were processed for histological analysis. Ear sections were stained with toluidine blue-eosin, and degranulated MCs were counted. The scale bar in histological images represents 25 μm. The red arrows indicate degranulated MCs and the black arrows indicate intact MCs. The representative images were captured at a total magnification of 400×. The representative images (<b>A</b>,<b>C</b>) and values (<b>B</b>,<b>C</b>) were generated from three independent experiments. The values (<b>B</b>,<b>C</b>) are presented as the mean ± SEM. Statistical significance is indicated by an asterisk; ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Pro10-1D suppresses the activity of Lyn and Fyn kinases in vitro. (<b>A</b>) BMMCs (3.0 × 10<sup>5</sup> cells/well) were pre-incubated with Pro10-1D or PP2 for 30 min and then stimulated with 1 μM ionomycin or 300 nM thapsigargin for 15 min. (<b>B</b>,<b>C</b>) KinaseProfiler radiometric protein kinase assays were performed with Lyn and Fyn kinase. The protocols used for the kinase assay are detailed in the <a href="#sec4-ijms-25-12138" class="html-sec">Section 4</a> “Materials and Methods”. (<b>A</b>–<b>C</b>) The data are presented as the mean ± SEM from two independent experiments. Statistical significance is indicated by an asterisk; ** <span class="html-italic">p</span> &lt; 0.01.</p>
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14 pages, 577 KiB  
Review
Infusion Reactions to Infliximab in Pediatric Patients with Inflammatory Bowel Disease
by Rajmohan Dharmaraj, Tess Pei Lemon, Rasha Elmaoued, Ricardo Orlando Castillo and Razan Alkhouri
Children 2024, 11(11), 1366; https://doi.org/10.3390/children11111366 - 10 Nov 2024
Viewed by 1074
Abstract
Infliximab (IFX) is a recombinant DNA-derived chimeric IgG monoclonal antibody protein that inhibits tumor necrosis factor alpha (TNF-α). IFX, like other agents derived from foreign proteins, can cause infusion reactions both during and after the infusion. The incidence of infusion reactions ranges between [...] Read more.
Infliximab (IFX) is a recombinant DNA-derived chimeric IgG monoclonal antibody protein that inhibits tumor necrosis factor alpha (TNF-α). IFX, like other agents derived from foreign proteins, can cause infusion reactions both during and after the infusion. The incidence of infusion reactions ranges between 0% and 15% in pediatric patients. The potential underlying mechanisms for these reactions may include anaphylaxis and anaphylactoid reactions, cytokine release syndrome, serum sickness-like reactions, and the development of antibodies against IFX. Several precautions can help reduce the risk of a new infusion reaction, such as a gradual increase in the infusion rate, scheduled infusions, and administering premedication or immunomodulators alongside IFX. Acute mild to moderate reactions often resolve spontaneously after a temporary cessation of the infusion or reduction in the infusion rate. Strategies like graded dose challenges and premedication can be utilized to prevent recurrence. In cases of severe reactions, desensitization or switching to an alternative biologic may be considered. This article aims to review the most recent guidelines for managing IFX-related infusion reactions in pediatric patients with inflammatory bowel disease (IBD), relying on the best available evidence. Full article
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<p>Algorithm for management of infliximab infusion reactions.</p>
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12 pages, 273 KiB  
Article
Natural History and Risk Factors of Hymenoptera Venom Allergy in Dogs
by Edwin Chapman, Erin Ashley West, Mitja Kosnik, Nina Maria Fischer, Claude Favrot, Leo Beeler and Ana Rostaher
Animals 2024, 14(22), 3220; https://doi.org/10.3390/ani14223220 - 10 Nov 2024
Viewed by 761
Abstract
Hymenoptera, which includes honeybees, wasps, bumblebees, and hornets, is an order of the class Insecta, whose venom can induce anaphylactic reactions in dogs. While several studies have investigated the natural histories and risk factors of Hymenoptera venom allergy (HVA) in humans, only limited [...] Read more.
Hymenoptera, which includes honeybees, wasps, bumblebees, and hornets, is an order of the class Insecta, whose venom can induce anaphylactic reactions in dogs. While several studies have investigated the natural histories and risk factors of Hymenoptera venom allergy (HVA) in humans, only limited information is available on canine patients. Therefore, the aim of this study was to identify risk factors leading to severe systemic reactions (SSRs) and to explore the natural history of these patients. This was achieved with an inquiry into the case histories of 178 dogs that were stung by Hymenoptera and presented to the Vetsuisse Faculty Animal Hospital of the University of Zurich between 2018 and 2022. Dogs under two years old, dogs that weighed under 10 kg, purebred dogs, and dogs that were stung in the oral cavity were at a greater risk of developing SSRs. Almost two thirds of patients with SSRs experienced the same or worse symptoms after subsequent stings and >40% of patients with local reactions developed SSRs when stung again. Next to providing valuable clinical information about HVA in dogs, these findings strongly support the recommendation of venom immunotherapy (VIT) for patients with HVA. Full article
(This article belongs to the Section Veterinary Clinical Studies)
14 pages, 1892 KiB  
Article
Safety and Immunogenicity of Intranasal Razi Cov Pars as a COVID-19 Booster Vaccine in Adults: Promising Results from a Groundbreaking Clinical Trial
by Mohammad Hossein Fallah Mehrabadi, Monireh Hajimoradi, Ali Es-haghi, Saeed Kalantari, Mojtaba Noofeli, Ali Rezaei Mokarram, Seyed Hossein Razzaz, Maryam Taghdiri, Ladan Mokhberalsafa, Fariba Sadeghi, Vahideh Mohseni, Safdar Masoumi, Rezvan Golmoradi-Zadeh, Mohammad Hasan Rabiee, Masoud Solaymani-Dodaran and Seyed Reza Banihashemi
Vaccines 2024, 12(11), 1255; https://doi.org/10.3390/vaccines12111255 - 5 Nov 2024
Viewed by 1539
Abstract
Protective antibodies in the upper respiratory tract prevent the spread of COVID-19 in the community. Intranasal vaccines could raise the specific secretory IgA and IgG levels. This is a single-center, randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and immunogenicity of Razi [...] Read more.
Protective antibodies in the upper respiratory tract prevent the spread of COVID-19 in the community. Intranasal vaccines could raise the specific secretory IgA and IgG levels. This is a single-center, randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and immunogenicity of Razi Cov Pars (RCP) intranasal recombinant protein subunit COVID-19 vaccine as a booster in adults. We compared specific IgG and IgA levels in the intranasal RCP group (n = 97) versus placebo (n = 96) in serum, saliva, and nasal mucosal secretions on days 0 and 14 and reported their Geometric Mean Ratios (GMR) and 95% confidence intervals (CI). We showed significant increases in IgA and IgG anti-RBD in the nasal mucosa in the RCP group, but their increase was not detectable in the serum and saliva. Anti-spike IgA in the nasal mucosa also increased in the RCP group compared to the placebo. This increase against the COVID-19 variant Omicron was also similar to that of the Wuhan. We detected no serious adverse reactions or anaphylaxis and all adverse events resolved completely during the follow-up period and were similar in both groups. Intranasal RCP is safe, stimulates the respiratory mucosal immunity, and could be a booster on various COVID-19 vaccines and be effective against new virus variants. Full article
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<p>Participant’s flow diagram.</p>
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<p>Frequency of solicited systemic adverse reactions by study groups during the first week following vaccination.</p>
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<p>Scatter plots of individual values and their geometric means for specific IgG and IgA antibody levels in the serum and nasal mucosal secretions of the study participants at the time of booster IN vaccination and two weeks after. (<b>A</b>): Serum Anti-RBD IgG levels; (<b>B</b>): Serum Anti-RBD IgA levels; (<b>C</b>): Nasal mucosal Anti-RBD IgG levels; (<b>D</b>): Nasal mucosal Anti-RBD IgA levels. ns, not significant, * <span class="html-italic">p</span>  &lt;  0.05, ** <span class="html-italic">p</span>  &lt;  0.01, *** <span class="html-italic">p</span>  &lt;  0.001.</p>
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<p>Scatter plots of individual values and their geometric means of nasal mucosal specific IgA anti-spike antibodies comparing the antibody response to Wuhan and Omicron variants in the study participants by study groups at the time of booster IN vaccination and two weeks after. ns, not significant, * <span class="html-italic">p</span>  &lt;  0.05, ** <span class="html-italic">p</span>  &lt;  0.01, *** <span class="html-italic">p</span>  &lt;  0.001.</p>
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<p>Scatter plots of individual values and their geometric means comparing the serum anti-Spike specific IgG in a subpopulation of phase III study participants in RAZI and Sinopharm groups in response to IN RCP or placebo (adjuvant), respectively, at the time of IN booster vaccination and two weeks after. * <span class="html-italic">p</span>  &lt;  0.05, ** <span class="html-italic">p</span>  &lt;  0.01, *** <span class="html-italic">p</span>  &lt;  0.001.</p>
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