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The article discusses the role of IL-1R2 expression in Tfr cells in regulating allergic anaphylaxis by influencing IgG versus IgE responses. The study conducted on mice with IL-1R2 deletion in Tfr cells showed an exacerbation of allergic anaphylaxis with increased IgE levels and reduced IgG responses. The findings suggest that IL-1R2 expression in Tfr cells may control the balance between IgG and IgE pathways in the germinal center response, impacting allergic reactions. [Extracted from the article]

Introduction: Novel treatments are being researched to develop more safe and effective protective medications for anaphylaxis. Camel whey protein (CWP) and baicalein (BAC, one of the major flavones) have multiple beneficial properties including anti-inflammatory and antioxidant activities. Methods: The current study investigated/compared the therapeutic protection of repeated intragastric administration of CWP (100 mg/kg body weight, as an animal extract) and BAC (10 mg/kg body weight, as a plant extract), before the challenge with ovalbumin (OVA) or receiving the compound 48/80 (C48/80), against mice models for IgE-independent and dependent anaphylaxes. Besides, their effects on mast cells (MCs) downstream cell signaling were explored. Results: The results revealed that CWP and BAC reduced the mortality rate, as compared with a MCs stabilizer "sulfasalazine (SSZ, 100 mg/kg body weight, intraperitoneally)," in both mice models. Furthermore, they prevented the MCs degranulation and significantly reduced (p <.05) lung tissue levels of cell signaling (p-AKT, p-ERK, and p-IκBα). Additionally, they decreased histamine, tryptase, leukotriene C4, prostaglandin D2, interleukin (IL)-4, and IL-10 levels in broncho-alveolar and peritoneal lavages in systemic anaphylaxis mice models. They also restored the stabilization of peritoneal MCs membrane in inverted light microscopy results accompanied by amelioration of the lung histology. Discussion: The present study provided evidence for the protective therapeutic effect of CWP and BAC against anaphylaxis. As a result, CWP and BAC may be used as preventative supplemented regimens for both non-vegetarian and vegetarian consumers to treat allergy through downregulation of MCs signal transduction pathways, and hence controlling the production of inflammatory mediators. [ABSTRACT FROM AUTHOR]

ContextType I hypersensitivity affects approximately one-third of the global population. As the pathophysiology underlying the development of type I hypersensitivity (asthma, food allergy, and anaphylactic shock, etc.) is complex and heterogeneous, animal model studies continue to be the key to identifying novel molecular pathways and providing therapeutic strategies.ObjectiveSelection of the animal model should be done with careful consideration of the protocol variables, animal species, and strains to accurately reflect the clinical symptoms typical of humans.MethodsThe following databases were searched: PubMed and Web of Science.Results and conclusionForeign allergens include allergenic proteins and chemical haptens. This review summarizes the various methods used for designing animal models of common allergenic protein-induced type I hypersensitivity, namely, passive anaphylaxis model, active systemic anaphylaxis/anaphylaxis shock model, food allergy model, asthma model, and IgE-mediated cell models. Additionally, we summarize shrimp tropomyosin-induced type I hypersensitivity models from our previous studies and discuss their advantages and limitations compared with that of ovalbumin-induced models.

Type I hypersensitivity, or so-called type I allergy, is caused by Th2-mediated immune responses directed against otherwise harmless environmental antigens. Currently, allergen-specific immunotherapy (AIT) is the only disease-modifying treatment with the potential to re-establish clinical tolerance towards the corresponding allergen(s). However, conventional AIT has certain drawbacks, including long treatment durations, the risk of inducing allergic side effects, and the fact that allergens by themselves have a rather low immunogenicity. To improve AIT, adjuvants can be a powerful tool not only to increase the immunogenicity of co-applied allergens but also to induce the desired immune activation, such as promoting allergen-specific Th1- or regulatory responses. This review summarizes the knowledge on adjuvants currently approved for use in human AIT: aluminum hydroxide, calcium phosphate, microcrystalline tyrosine, and MPLA, as well as novel adjuvants that have been studied in recent years: oil-in-water emulsions, virus-like particles, viral components, carbohydrate-based adjuvants (QS-21, glucans, and mannan) and TLR-ligands (flagellin and CpG-ODN). The investigated adjuvants show distinct properties, such as prolonging allergen release at the injection site, inducing allergen-specific IgG production while also reducing IgE levels, as well as promoting differentiation and activation of different immune cells. In the future, better understanding of the immunological mechanisms underlying the effects of these adjuvants in clinical settings may help us to improve AIT. [ABSTRACT FROM AUTHOR]

Hymenoptera venom allergy (HVA) is an anaphylactic reaction that occurs after the sting of Hymenoptera insects: honeybee (Apis mellifera), wasp (Vespula vulgaris) or hornet (Vespa crabo). Hymenoptera insects can cause IgE-mediated hypersensitivity reactions in insect-sensitized patients, ranging from local to severe systemic reactions and even fatal anaphylaxis. Systemic allergic reactions (SAR) after Hymenoptera insect stings have been reported in up to 7.5% of adults and up to 3.4% of children. They can be limited to the skin or cause severe reactions such as dizziness, dyspnea, nausea, and loss of consciousness, shock, cardiac or respiratory arrest. Patients with HVA are advised to carry an emergency kit consisting of an epinephrine auto-injector (AAI), H1-antihistamines and corticosteroids depending on the severity of the previous SAR. The only treatment that can potentially prevent SAR is immunotherapy with the appropriate venom (VIT). Venom immunotherapy (VIT) has been reported to be effective in 77%-84% of patients treated with bee venom and in 91%-96% of patients treated with wasp venom. The latest European Academy of Allergy and Clinical Immunology (EAACI) guidelines provide evidence-based recommendations for the use of VIT. It is recommended in children and adults who are hypersensitive to the venom because it leads to a significant improvement in quality of life-compared to wearing an adrenaline auto-injector. By receiving increasing doses of venom over 3 to 5 years, VIT leads to a change in the immune response and tolerance to the respective venom. Molecular diagnostics, which uses recombinant allergens, enables detection of true sensitization and thus improves the selection of appropriate venom for long-term VIT. This review aims to provide information on immunotherapy recommendations, as well as risk factors for SAR during and after VIT.

In view of increased incidence of IgE-mediated diseases in Russia and worldwide, the efforts of various research groups are focused on studying the mechanisms that trigger the process of switching B-lymphocytes to IgE synthesis upon human exposure to harmless allergens, including the role of various antigen-presenting cells (APCs) in this process. However, the role of distinct APCs upon long-term penetration of low antigen doses via the tissue barriers, is yet poorly understood, as well as specific features of these events upon entrance of the antigen through the subcutaneous adipose tissue which contains tissueassociated lymphoid clusters (TALC).The aim of this work was to determine the relationship between the local accumulation of various APCs in the subcutaneous adipose tissue and development of early IgE production in a clinically relevant experimental model of allergy with long-term administration of low allergen doses. In this experimental model, specific IgE synthesis is induced, with minimal concomitant IgG production, thus mimicking the situation observed in patients with clinically sound allergies. BALB/c mice were immunized for 4 weeks subcutaneously in the withers area or intraperitoneally with low (100 ng) or high (10 μg) doses of the model allergen (ovalbumin). Blood samples were taken weekly from mice for ELISA testing, to determine the production of specific antibodies. Provocation tests were performed with high dose of the allergen, and adipose tissue samples were taken from the site of antigen injection for flow cytometric assays, in order to evaluate the contents of various APC subpopulations. Specific IgE production was induced mainly by subcutaneous injection of the antigen at low doses (100 ng) into the area of withers. When using this experimental regimen, we observed accumulation of classical CD11b+ cells in adipose tissue at the withers site, but not in the peritoneal adipose tissue, in absence of CD11b- classical, inflammatory or plasmacytoid, dendritic cells. These findings coincided in time with increased production of specific IgE on days +14 to +21. Accumulation of CD11b+CD11c- macrophages and their CD206+ M2 subpopulations at early terms (days +7 and +21) was also observed only after subcutaneous injection of the antigen into the withers area. The high-dose antigen injection (10 μg) which mediated IgG1 production to greater extent than production of IgE, led to earlier accumulation of CD11b+ classical dendritic cells (on day 7th), and to the absence of macrophage accumulation at later stages (day 21th). Thus, the early start of specific IgE production upon low-dose injection of the antigen into the subcutaneous adipose tissue may be associated with its presentation by CD11b+ classical dendritic cells in the presence of CD11b+CD11c- macrophages.

To explore the differences in type I hypersensitivity-induced inflammatory response among children of different age groups with acute appendicitis. We selected children diagnosed with "acute appendicitis" who underwent surgery in the Department of General Surgery of Anhui Provincial Children's Hospital from January 2022 to June 2022 and collected their basic data. We divided them into two groups according to age: the infant group (less than 3 years old) and the pediatric group (3–14 years old). The gender, age, onset time, hospital stay, preoperative white blood cells, percentage of neutrophils, C-reactive protein (CRP), and enzyme-linked immunosorbent assay (ELISA) were collected to determine the levels of immunoglobulin E (IgE), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6), and interleukin-9 (IL-9) in appendicular lavage fluid, and the differences between the two groups were compared. There were 15 children in the infant group and 15 in the pediatric group. There was no significant difference between the two groups with respect to onset time and gender. The hospitalization time in the pediatric group was (5.7 ± 2.1) d, the preoperative white blood cells were (14.3 ± 3.7) × 10^9/mL, neutrophil percentage was (84.5 ± 6.3)%, and CRP was (20.0 ± 17.9) mg/mL. The hospitalization time of the infant group was (8.0 ± 3.1) d, the preoperative white blood cells were (19.0 ± 3.8) × 10^9/mL, neutrophil percentage was (77.8 ± 10.4)%, and CRP was (42.5 ± 25.0) mg/mL. The differences between the two groups were significant. There was no significant difference in IL-5 concentration between the two groups in the appendicular lavage fluid. IgE (610.74 ± 72.56) ng/mL, IL-4 (30.80 ± 12.04) ng/mL, IL-6 (118.09 ± 14.29) ng/mL, IL-9 (133.94 ± 16.00) ng/mL were found in the infant group, and IgE (495.61 ± 95.09) ng/mL, IL-4 (22.68 ± 7.05) ng/mL, IL-6 (98.22 ± 22.18) ng/mL and IL-9 (107.86 ± 27.34) ng/mL were found in the pediatric group, and the differences between the two groups were statistically significant. The inflammatory response in children with acute appendicitis was associated with type I hypersensitivity-induced inflammatory responses, and the type I hypersensitivity was more intense in children in the lower age group. • Explored the possible pathogenesis of acute appendicitis in children. • Explore the differences in type I hypersensitivity-induced specific inflammatory response among children of different age groups with acute appendicitis. • The inflammatory response in children with acute appendicitis was associated with type I hypersensitivity-induced specific inflammatory responses. • The type I hypersensitivity was more intense in children in the lower age group. [ABSTRACT FROM AUTHOR]

Platelet-activating factor (PAF) is a potent classical lipid mediator that plays a critical role in various diseases such as allergy and nervous system disorders. In the realm of allergy, previous studies suggested that PAF is generated in response to extracellular stimuli and contributes to allergic reactions via PAF receptor (PAFR). However, the sources of endogenous PAF and its pathophysiological dynamics remain largely elusive in vivo. Here, we report that rapid and local PAF generation completely depends on lysophospholipid acyltransferase 9 (LPLAT9, also known as LPCAT2) expressed in mast cells in IgE-mediated passive cutaneous anaphylaxis. However, we found that LPLAT9 knockout (KO) mice did not display attenuated vascular leakage. Additionally, decreased vascular leakage was observed in PAFR KO mice, but not in endothelial cell-specific mice in this model. These divergences highlight a yet unsolved complexity of the biological functions of PAF and PAFR in a pathophysiological process. • PAF biosynthesis depends on lysophospholipid acyltransferase 9 (LPLAT9, also known as LPCAT2) in vivo. • LPLAT9 deficiency does not attenuate cutaneous anaphylaxis. • PAFR deficiency, but not PAFR endothelial cell-specific deficiency attenuates cutaneous allergic reactions. • Present study provides revised insights to the biological functions of PAF/PAFR signaling. [ABSTRACT FROM AUTHOR]

Type I hypersensitivity reactions, also known as allergic reactions or anaphylactic reactions. The mechanism of anaphylaxis involves the release of mediators from mediator cells. The degranulation of mast cells and basophils causes an exaggerated immune response and causes the signs and symptoms of anaphylaxis. Red dragon fruit peel contains secondary metabolites such as triterpenoid flavonoids and steroids. This study was an in vitro study of the ethanol extract of red dragon fruit peel (Hylocereus polyrhizuz) on the mast cells of male white mice induced by antigen. Five variations of the concentration used are 25; 50;100;200;400µg/mL. The percentage of mast cell degranulation by red dragon fruit peel extract at concentrations of 25;50;100;200 dan 400 µg/mL is 75.27; 69.05; 64.04, 56.61; 45.17; dan 27.88%. There Red dragon fruit peel extract had a significant effect in inhibiting mast cell degranulation (p

Type I hypersensitivity is an immediate immune reaction that involves IgE-mediated activation of mast cells. Activated mast cells release chemical mediators, such as histamine and lipid mediators, which cause allergic reactions. Recent developments in detection devices have revealed that mast cells simultaneously release a wide variety of lipid mediators. Mounting evidence has revealed that mast cell-derived mediators exert both pro- and anti-inflammatory functions and positively and negatively regulate the development of allergic inflammation. This review presents the roles of major lipid mediators released from mast cells. Author believes this review will be helpful for a better understanding of the pathogenesis of allergic diseases and provide a new strategy for the diagnosis and treatment of allergic reactions.

Abstract Background Insulin hypersensitivity is rare, but challenging for individuals with diabetes. The prevalence of insulin allergy has decreased since the introduction of human recombinant insulin preparations. Hypersensitivity reactions range from injection site erythema and swelling, to anaphylaxis. While some reactions are to excipients (zinc, protamine, metacresol), many are to recombinant insulin itself. We present a case of type 1 hypersensitivity to various preparations of insulin in a patient with insulin-dependent type 2 diabetes mellitus (T2DM). Case presentation A 61-year-old woman with a 30-year history of insulin-dependent T2DM was referred for evaluation of reactions to insulin. She had two episodes over 5-months; both required Emergency Department visits and epinephrine administration. The first episode entailed a burning sensation of the extremities and nausea, immediately after injecting NovoRapid® insulin. The second event entailed a similar reaction but this time there was also angioedema of the upper airway with difficulty breathing and hypotension, immediately after injecting Levemir® and NovoRapid®, and taking metformin. There were no cofactors such as exercise, infectious illness, or NSAIDs use. Skin testing was performed with metformin, Lantus®, Humalog®, NovoRapid®, glulisine, insulin regular, NPH, Levemir® and the excipient protamine, as per published testing concentrations. Metacresol was not tested as its use was restricted by the hospital pharmacy. Insulin preparations with and without metacresol were included in testing however. A clinic staff served as a negative control. The patent had negative testing with protamine, but sensitization to all insulin preparations. Metformin skin testing and challenge along with latex IgE were negative. Subsequently, she underwent intentional weight loss of 70 lb, and was started on oral hypoglycemics with good effect. Conclusions Our case highlights the importance of diagnosing insulin allergy through a detailed history and focused testing. Therapeutic strategies include avoidance and insulin alternatives, alternate insulin preparations, or desensitization. In severe recurrent hypersensitivity reactions, Omalizumab or pancreatic transplantation have been effective.

Veronica Storino,1 Juliana Muñoz-Ortiz,2 Valeria Villabona-Martinez,3 Juan Diego Villamizar-Sanjuán,3 William Rojas-Carabali,3 Alejandra de-la-Torre3 1Faculty of Medicine, Universidad de los Andes, Bogotá, Colombia; 2Escuela Barraquer, Research Group, Escuela Superior de Oftalmología, Instituto Barraquer de América, Bogotá, Colombia; 3Neuroscience Research Group “NeURos”, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, ColombiaCorrespondence: Alejandra de-la-TorreNeuroscience Research Group “NeURos”, Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Carrera 24 # 63C - 69, Bogotá, ColombiaTel +57 3102482196Email alejadelatorre@yahoo.comPurpose: To report the case of a patient with multiple food allergies comorbid with multiple chemical sensitivity (MCS) who was misdiagnosed on various occasions, resulting in a negative impact on the patient’s personal and social life.Case Report: We present the case of a 43-year-old Colombian women with multiple food allergies concomitant with MCS. Symptoms started with a mild reaction to insecticides, car exhaust smoke, and perfumes and gradually evolved into a severe reaction to her environment. She also presented recurrent episodes of clinical reactivity to foods and persistent elevated IgE levels, as well as several life-threatening anaphylactic reactions. Alternative and allopathic therapies were applied, but her symptoms persisted. Various diagnoses were made before the definitive diagnosis.Conclusion: MCS is an unusual entity of unknown pathophysiology that can, on rare occasions, coexist with food allergies. Early recognition and multidisciplinary treatment are required as these entities have a major impact on the patient’s quality of life. We present the first Latin American case regarding the association of the two diseases.Keywords: type I hypersensitivity, idiopathic environmental intolerance, environmental exposure, food allergy

Allergy is becoming an intensifying disease among the world population, particularly in the developed world. Once allergy develops, sufferers are permanently trapped in a hyper-immune response that makes them sensitive to innocuous substances. The immune pathway concerned with developing allergy is the Th2 immune pathway where the IgE antibody binds to its Fc∊RI receptor on Mast and Basophil cells. This paper discusses a protocol that could disrupt the binding between the antibody and its receptor for a potential permanent treatment. Ten proteins were computationally designed to display a human IgE motif very close in proximity to the IgE antibody’s Fc∊RI receptor’s binding site in an effort for these proteins to be used as a vaccine against our own IgE antibody. The motif of interest was the FG loop motif and it was excised and grafted onto a Staphylococcus aureus protein (PDB ID 1YN3), then the motif + scaffold structure had its sequence re-designed around the motif to find an amino acid sequence that would fold to the designed structure correctly. These ten computationally designed proteins showed successful folding when simulated using Rosetta’s AbinitioRelax folding simulation and the IgE epitope was clearly displayed in its native three-dimensional structure in all of them. These designed proteins have the potential to be used as a pan anti-allergy vaccine. This work employedin silicobased methods for designing the proteins and did not include any experimental verifications.

Drug hypersensitivity is defined as an untoward response to medication which is noxious and unintended, and which occurs at doses normally used in human either for the prophylaxis, diagnosis, or therapy of disease or for the modification of physiological function. Drug hypersensitivity is common and may cause emergency condition until death. The incidence of drug hypersensitivity-related hospitalizations has usually been assessed within hospitals. The aim of this study is to determine the profile of drug hypersensitivity patients hospitalized at Dr. Soetomo Hospital in 6 months period from January to June 2016. This study was a descriptive retrospective study on medical records of drug hypersensitivity patients hospitalized in Dr. Soetomo Hospital in 6 months period. The patient’s demographic data, the type of hypersensitivity reaction, and the final outcome of the hospitalization were collected. Within the 6 months period, there were 16 drug hypersensitivity patients hospitalized in Dr. Soetomo Hospital. Most of them are female (56.25%), and aged between 46-55 years (25%). There were 4 patients (25%) with type I hypersensitivity: urticaria, angioedema and anaphylaxis; while type IV hypersensitivity occured in 12 patients (75%): Stevens-Johnson syndrome, Stevens-Johnson syndrome-Toxic Epidermal Necrolysis overlap, erythroderma, maculopapular drug eruptions, and DRESS. Most of the patients (87.5%) had favorable outcome after hospitalization. There were 16 patients with drug hypersensitivity reaction hospitalized in Dr. Soetomo Hospital, Surabaya in 6 months period. Most of them were female and had type IV hypersensitivity reactions.

Diphenhydramine is an H1 receptor antagonist used to control urticaria and other allergic signs caused by type I hypersensitivity reactions in horses (Equus caballus). Limited studies have been conducted on pharmacokinetics of this drug in horses, with no studies involving oral formulations. Our study investigated pharmacokinetics of an oral diphenhydramine formulation compared to intravenous administration in non‐fasted adult horses. Six healthy horses underwent a single administration of three different doses of diphenhydramine (1 mg/kg intravenously, 1 mg/kg intragastrically, and 5 mg/kg intragastrically) with a two‐week washout period between doses. Bioavailability of intragastric diphenhydramine was less than one percent and six percent for 1 mg/kg and 5 mg/kg intragastric doses, respectively. This poor bioavailability is similar to what is reported in dogs. Two of six horses experienced transient side effects after intravenous diphenhydramine administration, emphasizing the need for determining therapeutic plasma levels in efforts to determine the lowest effective dose minimizing risk of adverse effects. The main conclusion of our study was that oral diphenhydramine at doses up to 5 mg/kg are unlikely to achieve therapeutic plasma levels in adult horses. [ABSTRACT FROM AUTHOR]

Allergy, formally called type I (or immediate) hypersensitivity is one of four or more forms of hypersensitivity manifesting in various forms like, Atopic eczema, Allergic urticaria, Allergic rhinitis, Allergic asthma,, Food allergy, etc. The growing incidence of Food allergy needs attention since its burden is mainly on children and adolescents. Various factors has been attributed to the growing incidence of food allergy such as food habits, cooking habits, cultural differences, various developmental parameters and exchange of food products. The World Allergy Organization has estimated 220 to 550 million people suffering from food allergy with a large chunk of population from the developed countries. No concrete data is available on status of food allergy in India though some sporadic research has been published. In spite of diligent research worldwide, an effective mechanism to cure this condition has not been evolved till today. Since effectiveness of homeopathy has been proved in various allergy conditions, the modality of using the same has been explored in this article. [ABSTRACT FROM AUTHOR]

The binding of nickel by immune proteins can manifest as Type IV contact dermatitis (Ni-specific T cells mediated) and less frequently as Type I hypersensitivity with both mechanisms remaining unknown to date. Since there are reports of patients co-manifesting the two hypersensitivities, a common mechanism may underlie both the TCR and IgE nickel binding. Focusing on Trastuzumab and Pertuzumab IgE variants as serendipitous investigation models, we found Ni-NTA interactions independent of Her2 binding to be due to glutamine stretches. These stretches are both Ni-inducible and in fixed pockets at the antibody complementarity-determining regions (CDRs) and framework regions (FWRs) of both the antibody heavy and light chains with influence from the heavy chain constant region. Comparisons with TCRs structures revealed similar interactions, demonstrating the possible underlying mechanism in selecting for Ni-binding IgEs and TCRs respectively. With the elucidation of the interaction, future therapeutic antibodies could also be sagaciously engineered to utilize such nickel binding for biotechnological purposes.

Background: Insulin hypersensitivity is rare, but challenging for individuals with diabetes. The prevalence of insulin allergy has decreased since the introduction of human recombinant insulin preparations. Hypersensitivity reactions range from injection site erythema and swelling, to anaphylaxis. While some reactions are to excipients (zinc, protamine, metacresol), many are to recombinant insulin itself. We present a case of type 1 hypersensitivity to various preparations of insulin in a patient with insulin-dependent type 2 diabetes mellitus (T2DM). Case presentation: A 61-year-old woman with a 30-year history of insulin-dependent T2DM was referred for evaluation of reactions to insulin. She had two episodes over 5-months; both required Emergency Department visits and epinephrine administration. The first episode entailed a burning sensation of the extremities and nausea, immediately after injecting NovoRapid® insulin. The second event entailed a similar reaction but this time there was also angioedema of the upper airway with difficulty breathing and hypotension, immediately after injecting Levemir® and NovoRapid®, and taking metformin. There were no cofactors such as exercise, infectious illness, or NSAIDs use. Skin testing was performed with metformin, Lantus®, Humalog®, NovoRapid®, glulisine, insulin regular, NPH, Levemir® and the excipient protamine, as per published testing concentrations. Metacresol was not tested as its use was restricted by the hospital pharmacy. Insulin preparations with and without metacresol were included in testing however. A clinic staff served as a negative control. The patent had negative testing with protamine, but sensitization to all insulin preparations. Metformin skin testing and challenge along with latex IgE were negative. Subsequently, she underwent intentional weight loss of 70 lb, and was started on oral hypoglycemics with good effect. Conclusions: Our case highlights the importance of diagnosing insulin allergy through a detailed history and focused testing. Therapeutic strategies include avoidance and insulin alternatives, alternate insulin preparations, or desensitization. In severe recurrent hypersensitivity reactions, Omalizumab or pancreatic transplantation have been effective. [ABSTRACT FROM AUTHOR]

The binding of nickel by immune proteins can manifest as Type IV contact dermatitis (Ni-specific T cells mediated) and less frequently as Type I hypersensitivity with both mechanisms remaining unknown to date. Since there are reports of patients co-manifesting the two hypersensitivities, a common mechanism may underlie both the TCR and IgE nickel binding. Focusing on Trastuzumab and Pertuzumab IgE variants as serendipitous investigation models, we found Ni-NTA interactions independent of Her2 binding to be due to glutamine stretches. These stretches are both Ni-inducible and in fixed pockets at the antibody complementarity-determining regions (CDRs) and framework regions (FWRs) of both the antibody heavy and light chains with influence from the heavy chain constant region. Comparisons with TCRs structures revealed similar interactions, demonstrating the possible underlying mechanism in selecting for Ni-binding IgEs and TCRs respectively. With the elucidation of the interaction, future therapeutic antibodies could also be sagaciously engineered to utilize such nickel binding for biotechnological purposes. [ABSTRACT FROM AUTHOR]

Allergic diseases represent a global health and economic burden of increasing significance. The lack of disease-modifying therapies besides specific allergen immunotherapy (AIT) which is not available for all types of allergies, necessitates the study of novel therapeutic approaches. Exosomes are small endosome-derived vesicles delivering cargo between cells and thus allowing inter-cellular communication. Since immune cells make use of exosomes to boost, deviate, or suppress immune responses, exosomes are intriguing candidates for immunotherapy. Here, we review the role of exosomes in allergic sensitization and inflammation, and we discuss the mechanisms by which exosomes could potentially be used in immunotherapeutic approaches for the treatment of allergic diseases. We propose the following approaches: (a) Mast cell-derived exosomes expressing IgE receptor FcεRI could absorb IgE and down-regulate systemic IgE levels. (b) Tolerogenic exosomes could suppress allergic immune responses via induction of regulatory T cells. (c) Exosomes could promote TH1-like responses towards an allergen. (d) Exosomes could modulate IgE-facilitated antigen presentation.

Drug hypersensitivity is defined as an untoward response to medication which is noxious and unintended, and which occurs at doses normally used in human either for the prophylaxis, diagnosis, or therapy of disease or for the modif ication of physiological function. Drug hypersensitivity is common and may cause emergency condition until death. The incidence of drug hypersensitivity-related hospitalizations has usually been assessed within hospitals. The aim of this study is to determine the profile of drug hypersensitivity patients hospitalized at Dr. Soetomo Hospital in 6 months period from January to June 2016. This study was a descriptive retrospective study on medical records of drug hypersensitivity patients hospitalized in Dr. Soetomo Hospital in 6 months period. The patient's demographic data, the type of hypersensitivity reaction, and the final outcome of the hospitalization were collected. Within the 6 months period, there were 16 drug hypersensitivity patients hospitalized in Dr. Soetomo Hospital. Most of them are female (56.25%), and aged between 46-55 years (25%). There were 4 patients (25%) with type I hypersensitivity: urticaria, angioedema and anaphylaxis; while type IV hypersensitivity occured in 12 patients (75%): Stevens-Johnson syndrome, Stevens- Johnson syndrome-Toxic Epidermal Necrolysis overlap, erythroderma, maculopapular drug eruptions, and DRESS. Most of the patients (87.5%) had favorable outcome after hospitalization. There were 16 patients with drug hypersensitivity reaction hospitalized in Dr. Soetomo Hospital, Surabaya in 6 months period. Most of them were female and had type IV hypersensitivity reactions. [ABSTRACT FROM AUTHOR]

Competing Interests: None disclosed.

Background The efficacy of omalizumab (anti-IgE) and increased IgE levels in patients with chronic spontaneous urticaria (CSU) suggest autoallergic mechanisms. Objective We sought to identify autoallergic targets of IgE in patients with CSU. Methods Serum samples of patients with CSU together with those of patients with idiopathic anaphylaxis and healthy control subjects (7 of each) were screened for IgE autoantibodies by using an array of more than 9000 proteins. Sera of 1062 patients with CSU and 482 healthy control subjects were used in an IgE-anti–IL-24–specific ELISA to investigate the association of IgE-anti-IL-24 and CSU. Results By using array analyses, more than 200 IgE autoantigens were found in patients with CSU that were not found in control subjects. Of the 31 IgE autoantigens detected in more than 70% of patients, 8 were soluble or membrane bound and expressed in the skin. Of these, only IgE autoantibodies to IL-24 were found in all patients with CSU. In vitro studies showed IL-24 to release histamine from human mast cells sensitized with purified IgE of patients with CSU but not control subjects. By using ELISA, mean ± SD levels of IgE-anti–IL-24 were 0.52 ± 0.24 IU/mL in patients with CSU and 0.27 ± 0.08 IU/mL in control subjects, with 80% of patients with CSU but only 20% of control subjects having levels greater than 0.33 IU/mL ( P < .0001). IgE-anti–IL-24 showed acceptable predictive properties for CSU, with a likelihood ratio of 3.9. Clinically, IgE-anti–IL-24 levels showed an association with disease activity, as assessed by the urticaria activity score and with reduced basophil counts. Conclusion Our findings show that patients with CSU frequently exhibit IgE autoantibodies against many autoantigens and that IL-24 is a common, specific, and functional autoantigen of IgE antibodies in patients with CSU. [ABSTRACT FROM AUTHOR]

Résumé L’exposition aux enzymes microbiennes chez le personnel d’usines de fabrication de détergents peut conduire à une sensibilisation IgE dépendante et les exposer à des évènements allergiques graves. L’objectif de la surveillance par le médecin du travail est de repérer précocement une sensibilisation de ces salariés avant que des symptômes allergiques ne surviennent. L’industrie des détergents s’appuie sur une longue expérience et des recommandations strictes pour éviter l’apparition de symptômes chez ses salariés. L’Association internationale de la savonnerie, de la détergence et des produits d’entretien basée à Bruxelles propose des mesures de surveillance individuelle des salariés (questionnaires, analyse de la fonction pulmonaire…) ainsi que des mesures de prévention collectives strictes telles que le contrôle de la qualité de l’air. Des programmes de surveillance des salariés basés sur la réalisation de tests cutanés ont montré leur efficacité pour le dépistage précoce de cette sensibilisation. Entre 2006 et 2010, dans plus de 100 usines à travers le monde, il a été décrit un taux d’incidence annuelle de nouvelles sensibilisations inférieur à 1 % et d’allergies professionnelles inférieur à 0,1 %. Nous décrivons les caractéristiques originales de ce modèle appliqué à une usine sur le territoire français. Exposure to microbial enzymes among staff working in detergent manufacturing facilities can result in IgE-dependent sensitisation with risk of serious allergic events. The purpose of monitoring by an occupational health doctor is to enable early detection of sensitisation in employees before actual allergic symptoms occur. The detergents industry relies on extensive experience and strict recommendations to avoid the onset of symptoms in staff. The International Association for Soaps, Detergents and Maintenance Products based in Brussels proposes individual surveillance measures for staff members (e.g. questionnaires, pulmonary function testing) as well as strict preventive measures at the collective level such as air quality controls. Staff surveillance programs based on skin testing have proved effective in the early detection of such sensitisation. Between 2006 and 2010, in more than 100 factories worldwide, the annual incidence of new cases of sensitisation was less than 1% while that of occupational allergies was below 0.1%. Herein, we describe the novel characteristics of this model as applied to a factory on French territory. [ABSTRACT FROM AUTHOR]

• Severe appendicitis negatively correlated with serum IgE levels. • CRP, IgE, IL-6, and IL-13 were independent risk factors for CAA. • The combination of these serological markers could be used to diagnose CAA. In this study, the diagnostic value of C-reactive protein (CRP), interleukin-6 (IL)-6, and specific markers for type I hypersensitivity were evaluated in pediatric patients with severe acute appendicitis. A total of 140 pediatric patients with "acute appendicitis" who underwent surgery at the Department of General Surgery of the Anhui Provincial Pediatric Patients' Hospital between December 2022 and April 2023 were studied retrospectively. The data collected included the gender, age, onset time, white blood cell count (WBC), CRP, procalcitonin (PCT), serum IgE, serum IL-4, serum IL-5, serum IL-6, serum IL-9, and serum IL-13 levels. The pediatric patients were divided into two groups based on the intraoperative situation and postoperative pathology: the non-complicated acute appendicitis group (NCAA) and the complicated acute appendicitis group (CAA). We analyzed the data from both groups using univariate and multivariate logistic regression models and constructed an ROC curve. The CAA group outperformed the NCAA group in terms of onset time, WBC, CRP, PCT, IgE, IL-6, IL-9, and IL-13 levels (P < 0.05), but there was no statistically significant difference between the two groups in terms of gender, IL-4, or IL-5 levels (P > 0.05). Then, significant independent variables were incorporated into multivariate logistic regression. According to the results, CRP, IgE, IL-6, and IL-13 are all independent risk factors for CAA. The OR and 95% CI for each factor are as follows: CRP (OR = 1.073, 95%CI: 1.010–1.140, P = 0.022), IgE (OR = 0.975, 95%CI: 0.952–0.999, P = 0.038), IL-6 (OR = 1.494, 95%CI: 1.052–2.121, P = 0.025), and IL-13 (OR = 1.310, 95%CI: 1.036–1.657, P = 0.024). The receiving operator characteristics analysis yielded area under the curve (AUC) values of 0.8187, 0.9083, 0.8947, and 0.8394, respectively, for CRP, IgE, IL-6, and IL-13, confirming their significance in the diagnosis of CAA (P < 0.05). Risk factors for CAA include CRP, IgE, IL-6, and IL-13. The combination of these serological markers can be used to diagnose CAA. [ABSTRACT FROM AUTHOR]

Epidemiological evidence indicates a significant relationship between exposure to diisononyl phthalate and allergic asthma. Despite this, the mechanism underlying this association remains unclear. Previous toxicological researches have suggested that the development of allergic asthma may involve the activation of endoplasmic reticulum stress (ERS) and the nuclear factor κ-B (NF-κB) pathways. Nevertheless, it is currently unknown whether these specific signaling pathways are implicated in diisononyl phthalate (DINP)-induced allergic asthma. The objective of this research was to understand how DINP exacerbates allergic asthma in Balb/c mice through ERS and NF-κB pathways. To systematically examine the aggravated effects of DINP in Balb/c mice, we measured airway hyperresponsiveness (AHR), lung tissue pathology, cytokines, and ERS and NF-κB pathway biomarkers. Additionally, we applied the ERS antagonist phenylbutyric acid (4-PBA) or the NF-κB antagonist pyrrolidine dithiocarbamate (PDTC) to verify the mediating effects of ERS and NF-κB on DINP-exacerbated allergic asthma. The results of our experiment show that oral DINP exposure may exacerbate airway hyperresponsiveness and airway remodeling. This deterioration is accompanied by an imbalance in immunoglobulin levels, Th17/Treg cells, ERS, and NF-κB biomarkers, leading to the activation of pro-inflammatory pathways. Furthermore, our study found that the blocking effect of 4-PBA or PDTC can inhibit the Th17/Treg imbalance and effectively alleviate symptoms resembling allergic asthma. In conclusion, ERS and NF-κB signaling pathways play an important role in regulating DINP-induced allergic asthma exacerbations. [Display omitted] • Exposure to diisononyl phthalate aggravates allergic asthma in Balb/c mice. • Endoplasmic reticulum stress and NF-κB pathway is involved in allergic asthma exacerbated by diisononyl phthalate. • Exposure to diisononyl phthalate triggers Th17/Treg immune imbalance in Balb/c mice. • 4-PBA or PDTC treatment can alleviate allergic asthma caused by combined exposure to ovalbumin and diisononyl phthalate. [ABSTRACT FROM AUTHOR]

A previous study revealed that fucoidan inhibited mast cell degranulation through the upregulation of galectin-9 in blood. The purpose of this study is to elucidate its mechanism using ovalbumin (OVA) induced anaphylaxis model mice (BALB/c, Female, 5-week-old) and mast cell line (RBL-2H3 cells). Oral administration of fucoidan after sensitization with OVA/Al(OH)3 inhibited reduction of rectal temperature induced by activation of mast cells. Fucoidan increased galectin-9 mRNA expression only in colonic epithelial cells. These results suggested that fucoidan could suppress the allergic symptoms in sensitized mice by inducing galectin-9 production from colonic epithelial cells. In addition, to check the influence of galectin 9 on the degranulation of mast cells, RBL-2H3 cell lines were treated directly with recombinant galectin-9. As expected, galectin-9 inhibited degranulation of RBL-2H3 cells pre-bound with IgE. Moreover, the residual amounts of IgE on RBL-2H3 cells were decreased by an addition of galectin-9. It was demonstrated that galectin-9 could remove IgE even if IgE was already bound to mast cells and suppress the mast cells degranulation induced by antigen. This study shows that fucoidan might become an effective therapeutic agent for patients already developed type I allergic diseases.

Azithromycin 1.5% ophthalmic solution (Azyter®, Thea Pharmaceuticals, Newcastle, UK) is an effective and well-tolerated option for the treatment of bacterial conjunctivitis and blepharitis, and has the advantage of a shorter treatment duration than other topical antibiotics. No acute allergic reaction has yet been reported in response to topical azithromycin eye drops. Here, we report two cases with unusual acute-type allergic reaction to topical azithromycin eye drops. A 63-year-old female patient and 67-year-old male patient treated for blepharitis with topical azithromycin 1.5% eye drops presented with epiphora, eyelid edema, chemosis, conjunctival injection, hyperemia, intensive papillary reaction, and rhinitis within 30 min of instillation. Upon cessation of the topical medication and administration of antiallergic therapy, both patients immediately showed dramatic improvement. Acute-type allergic reaction to topical azithromycin eye drops may be a rare side effect, but ophthalmologists should keep this possibility in mind and inform the patients about its potential occurrence. [ABSTRACT FROM AUTHOR]

Parthenium dermatitis is a distressing dermatitis caused by the air borne allergen of the Compositae weed Parthenium hysterophorus. Uncommon presentations, newer insights in pathogenesis and management of this "scourge" are discussed in this article.