Allergic Hypersensitivity Research Articles

TPC Functions in the Immune System.

Two-pore channels (TPCs) are novel intracellular cation channels, which play a key role in numerous (patho-)physiological and immunological processes. In this chapter, we focus on their function in immune cells and immune reactions. Therefore, we first give an overview of the cellular immune response and the partaking immune cells. Second, we concentrate on ion channels which in the past have been shown to play an important role in the regulation of immune cells. The main focus is then directed to TPCs, which are primarily located in the membranes of acidic organelles, such as lysosomes or endolysosomes but also certain other vesicles. They regulate Ca2+ homeostasis and thus Ca2+ signaling in immune cells. Due to this important functional role, TPCs are enjoying increasing attention within the field of immunology in the last few decades but are also becoming more pertinent as pharmacological targets for the treatment of pro-inflammatory diseases such as allergic hypersensitivity. However, to uncover the precise molecular mechanism of TPCs in immune cell responses, further molecular, genetic, and ultrastructural investigations on TPCs are necessary, which then may pave the way to develop novel therapeutic strategies to treat diseases such as anaphylaxis more specifically.

Ethical Considerations Surrounding Employment Mandated Coronavirus Disease 2019 Vaccination and Allergy Skin Testing for the Coronavirus Disease 2019 Vaccine.

Ethical Considerations Surrounding Employment Mandated Coronavirus Disease 2019 Vaccination and Allergy Skin Testing for the Coronavirus Disease 2019 Vaccine.

Simultaneous microdetermination of different penicillin antibiotics residues for cross-contamination study in non-penicillin dosage forms

Cross-contamination of non-penicillin products with penicillin drugs can initiate life-threatening allergic hypersensitivity reactions, thus, all non-penicillin products should be tested for contamination before sale. This work describes a fast simple HPLC-DAD method for the simultaneous microdetermination of nine penicillin drugs for studying cross contamination of non-penicillin pharmaceutical dosage forms. Separation was done on C18 column with elution using 0.02 M phosphate buffer and methanol delivered in gradient mode and detection at 220 nm using DAD. Separation of all penicillins from non-penicillin drugs and their co-formulated excipients (methyl paraben, propyl paraben, sorbitol and sodium benzoate) with acceptable suitability parameters was obtained. The linearity ranges were within the range of 0.5–100 µg·mL−1 with good accuracy (Er% between −0.24 and 0.21 %) and precision (RSD% between 0.47 and 0.71 %). Good sensitivity was indicated by the obtained low limits of detection (0.1–1 µg·mL−1) for all the studied compounds. Successful application of the developed method in studying cross contamination of different non-penicillin products including salbutamol syrup and respiratory solution, miconazole cream, biperiden tablet, formoterol inhaler capsule and omeprazole capsule with residues of 9 penicillin drugs was performed without interference from all adjuvants. Henceforth, the proposed method can be recommended for the routine quality control to study and determine cross contamination of the non-penicillin facility with trace amounts of any of the studied penicillins with high accuracy and precision.

Efficacy of epinephrine rinse in allergen immunotherapy with aeroallergen and venom

Introduction In a suburban allergy outpatient office, the practice of epinephrine rinse of subcutaneous allergen immunotherapy (SCIT) syringes prior to injection has been employed for over 30 years with documented favorable clinical outcomes. A retrospective study was conducted to explore the effectiveness of epinephrine rinsing of SCIT syringes in managing local site reactions (LSR) in patients with allergen hypersensitivity. Methods Chart review of patients currently receiving SCITs was conducted using the clinical database at the outpatient office. 549 SCITs were reviewed, and 140 cases were traced to employ the use of epinephrine rinse to improve LSRs. The data was separated into allergic rhinitis and venom immunotherapy groups and was recorded for both build-up and maintenance phases. Results Out of 140 total patients requiring epinephrine rinse, 88.6% were in the allergic rhinitis group and 11.4% were in the venom group. In the allergic rhinitis group, 69.3% of patients and 87.5% in the venom group required epinephrine rinse during the build-up phase. In the allergic rhinitis group, 65.7% patients receiving SCIT at maintenance dose and 69.8% patients at build-up dose had resolution of LSR post-epinephrine rinse. In the venom group, 64.2% patients receiving SCITs at build-up dose improved LSR after epinephrine rinse. Conclusion Epinephrine rinse technique prior to injection showed favorable outcomes in over 60% of patients currently receiving treatment for allergen hypersensitivity. Epinephrine rinse is beneficial during the build-up phase of SCIT to manage LSR to effectively increase allergen dose.

Do products containing menthol exacerbate allergic rhinitis? A narrative review.

The aim of this paper is to review whether products containing menthol exacerbate allergic rhinitis. A literature survey was performed on PubMed, Google and Google Scholar concerning allergic rhinitis (AR). Allergic rhinitis is an inflammatory condition of the nasal mucosa characterized by wheeze, congestion, nasal pruritus and discharge, or any combination thereof. Menthol is a naturally occurring phytochemical, with the formula C10H20O. The L-isomeric form creates the typical odor of peppermints and causes a sensation of coolness when applied to the skin or mucosae. Inhaling menthol vapor is known to affect the respiratory system in a number of different ways. The cooling agent, menthol, is also recognized as a trigger for asthma, AR and urticaria. The menthol molecule stimulates the TRPM8 receptor and may stimulate histamine release in a dose-dependent manner from RBL-2H3 cell cultures. The addition of menthol to products produces symptomatic relief in some patients by providing an impression of freer nasal air flow. It does this by stimulating cold receptors on branches of the fifth cranial nerve. Menthol is capable of provoking allergic hypersensitivity reactions and disorders, including asthma, AR and urticaria. It may also trigger an anaphylactic response. The use of menthol-containing products is best avoided in cases where an allergic disorder exists.

Classification and management of hypersensitivity reactions

An inappropriate or excessive immune response to an antigen that has unfavourable effects is referred as a hypersensitivity reaction. People who have experienced at least one prior exposure to the antigen are more likely to have the symptoms. Nearly 60 years ago, Gell and Coombs first classified hypersensitivity reactions into four broad categories. Many forms of hypersensitivity reactions frequently occur at the same time, especially in allergic disorders. The purpose of this research is to review the available information about the classification and management of hypersensitivity reactions. Allergen-specific immunoglobulin E, which is associated with the high-affinity receptors of basophils and mast cells mediates type 1 hypersensitivity reactions. These receptors are cross-linked by allergens, which release mediators that elicit urticaria, angioedema, and anaphylaxis. Immunoglobulin G and immunoglobulin M attach to self-antigens on cell surfaces in type II reactions, which can lead to phagocytosis, and cytotoxicity that is complement-directed and antibody-dependent all of which can lead to tissue damage. Immune complexes of immunoglobulin G and immunoglobulin M with antigens, which deposit in tissues and directly harm organs, mediate type III reactions. T cells mediate type IV reactions which are delayed responses. In every case of allergic hypersensitivity, the trigger must be stopped right away. Antihistamines, glucocorticoids, and epinephrine are used to treat acute responses Some potential management techniques include drug allergy testing, graded challenges, desensitization, and/or choosing an alternative, non-cross-reactive substance. Further clinical research is however needed for the elaborated study of hypersensitive reactions and development of preventive strategies.

Tick bite as a risk factor for alpha-gal–specific immunoglobulin E antibodies and development of alpha-gal syndrome

BackgroundThe disaccharide galactose-α-1,3-galactose (alpha-gal) is expressed in mammals other than humans, apes, and old-world monkeys. In humans, elevated immunoglobulin E (IgE) antibodies specific for alpha-gal can result in allergic hypersensitivity known as alpha-gal syndrome (AGS). Case reports and series suggest that tick bites can induce alpha-gal–specific IgE (sIgE) antibodies. ObjectiveTo evaluate tick exposure as a risk factor for AGS and elevated alpha-gal sIgE level. MethodsWe conducted a case-control study comparing patients with AGS from a North Carolina allergy clinic with controls who were patients at a nearby internal medicine clinic. Cases and controls were administered a questionnaire to obtain information about demographics, home environment, outdoor activities, and recollection of tick bite. Serum samples taken at the time of enrollment were tested for total IgE, alpha-gal sIgE, and antibodies to other tick-borne pathogens. ResultsThe patients with AGS were more likely to recall finding a tick on themselves (odds ratio [OR], 11.20; 95% confidence interval [CI], 4.97-25.15), live near wooded forest (OR, 2.27; 95% CI, 0.92-5.55), and spend 17 or more hours per week outdoors in wooded areas (OR, 5.58; 95% CI, 2.56-12.19). The patients with AGS were also more likely to report 4 or more tick bites (OR, 33.05; 95% CI, 9.92-155.12) and reactions at the site of tick bites (OR, 7.93; 95% CI, 3.74-16.80). Furthermore, elevated alpha-gal sIgE level was observed in 33% of the controls and was associated with tick exposure in the controls (OR, 4.25; 95% CI, 2.21-8.18). ConclusionThe results define tick bite as a risk factor for AGS and elevated alpha-gal sIgE level.

Hypersensitivity reactions to small molecule drugs.

Drug hypersensitivity reactions induced by small molecule drugs encompass a broad spectrum of adverse drug reactions with heterogeneous clinical presentations and mechanisms. These reactions are classified into allergic drug hypersensitivity reactions and non-allergic drug hypersensitivity reactions. At present, the hapten theory, pharmacological interaction with immune receptors (p-i) concept, altered peptide repertoire model, and altered T-cell receptor (TCR) repertoire model have been proposed to explain how small molecule drugs or their metabolites induce allergic drug hypersensitivity reactions. Meanwhile, direct activation of mast cells, provoking the complement system, stimulating or inhibiting inflammatory reaction-related enzymes, accumulating bradykinin, and/or triggering vascular hyperpermeability are considered as the main factors causing non-allergic drug hypersensitivity reactions. To date, many investigations have been performed to explore the underlying mechanisms involved in drug hypersensitivity reactions and to search for predictive and preventive methods in both clinical and non-clinical trials. However, validated methods for predicting and diagnosing hypersensitivity reactions to small molecule drugs and deeper insight into the relevant underlying mechanisms are still limited.

AT9283, 1-Cyclopropyl-3-(3-(5-(Morpholinomethyl)-1H-Benzo[d]Imidazole-2-yl)-1H-Pyrazol-4-yl) Urea, Inhibits Syk to Suppress Mast Cell-Mediated Allergic Response.

Mast cells are an effector cell that plays a pivotal role in type I hypersensitive immune responses. Mast cells exist in connective tissues, such as skin and mucosal tissue, and contain granules which contain bioactive substances such as histamine and heparin in cells. The granules of mast cells are secreted by antigen stimulation to cause the type I allergic hypersensitivity. In addition, stimulated by antigen, mast cells synthesize and secrete various eicosanoids and cytokines. While AT9283 is known to have anticancer effects, the therapeutic effect of AT9283 on allergic disorders is completely unknown. In this study, it was found that AT9283 reversibly inhibited antigen-IgE binding-induced degranulation in mast cells (IC50, approx. 0.58 μM) and suppressed the secretion of the inflammatory cytokines IL-4 (IC50, approx. 0.09 μM) and TNF-α (IC50, approx. 0.19 μM). For a mechanism of mast cell inhibition, while not inhibiting Syk phosphorylation, AT9283 suppressed the activation of LAT, a downstream substrate protein of Syk, in a dose-dependent manner. As expected, AT9283 also inhibited the activation of PLCγ1 and Akt, downstream signaling molecules of Syk/LAT, and MAP kinases such as JNK, Erk1/2, and P38. In an in vitro protein tyrosine kinase assay, AT9283 directly inhibited Syk activity. Next, AT9283 dose-dependently inhibited passive cutaneous anaphylaxis (PCA), an IgE-mediated allergic acute response, in mice (ED50, approx. 34 mg/kg, p.o.). These findings suggest that AT9283 has potential to use as a new drug for alleviating the symptoms of IgE-mediated allergic disorders.

Case Report on Cutaneous Hypersensitivity Reactions to Orthopaedic Metallic Implant

Orthopaedic implants are made up of metal alloys which even though are inert may cause allergic hypersensitivity reactions which may systemic or cutaneous. We discuss a case of hypersensitivity reaction to orthopaedic forearm plating which was manifested locally thought out the body surface. Dermatologist and orthopaedic surgeon worked collaboratively to manage this scenario successfully. However, further research needs to be carried out for detection and prevention.

IKKβ increases neuropilin-2 and promotes the inhibitory function of CD9+ Bregs to control allergic diseases

Regulatory B cells (Bregs) potently suppress immune disorders, including allergic contact hypersensitivity (CHS). IKKβ overactivation is prominent in various inflammatory diseases. However, its effect on Bregs has not been defined. This study is to investigate the new regulator and inhibitory mechanism of Bregs. IkkβC46A transgenic mice with a Cys46 mutation, resulting in increased IKKβ activation, were employed for analysis. IL-10-competent CD9+ Bregs were expanded in IkkβC46A mice and B cell specific-IkkβC46A mutation mice. IkkβC46A mutant CD9+ Bregs had stronger suppressive effects on CD4+ and CD8+ T cells in vitro and CHS responses in vivo. The inhibitory CD9+ Bregs from IkkβC46A mice were characterized by upregulated Neuropilin 2 (Nrp2) and IL-10 in comparison with that of Ikkβwt mice. Interestingly, increased expression of Nrp2 was observed in CD9+ Bregs compared with that of CD9- B cells in wild-type mice. The suppressive activity of wild-type CD9+ Bregs in vitro was attenuated by inhibition of Nrp2 on Bregs or silencing its ligand Sema3f on CD4+ T cells. Our findings delineate a distinct role of IKKβ activation in enhancing Bregs to disturb the immune balance. It identifies Nrp2 as a novel regulatory molecule of Bregs that partly contributes to B cell-mediated immune tolerance.

Pharmacological modulation of TPC1 regulates inter-organellar Ca2+ homeostasis in immune cells and plays an important role in allergic hypersensitivity

Pharmacological modulation of TPC1 regulates inter-organellar Ca2+ homeostasis in immune cells and plays an important role in allergic hypersensitivity

Agreement of a clinical scoring system with allergic anaphylaxis in suspected perioperative hypersensitivity reactions: prospective validation of a new tool

BackgroundA clinical scoring system to estimate the likelihood that a reaction represents a perioperative immediate hypersensitivity reaction has been devised using a Delphi consensus process. Agreement of this clinical scoring system with the outcome of allergological assessment would allow the use of this tool in post-resuscitation and subsequent management of suspected perioperative immediate hypersensitivity reaction and potentially as a new standard reference for clinical investigations. MethodsWe prospectively scored 301 cases of suspected perioperative immediate hypersensitivity reaction according to the Hypersensitivity Clinical Scoring Scheme. Classification of cases was by allergological workup based on immediate and delayed investigations. The discrimination and calibration of the Hypersensitivity Clinical Scoring Scheme was compared with results from an expert panel of allergologists, skin testing, mast cell tryptase ratios, and specific IgE assays, as was agreement by Cohen's kappa coefficient. ResultsThe Hypersensitivity Clinical Scoring Scheme predicted cases of allergic perioperative immediate hypersensitivity reaction with comparable discrimination to an expert panel, mast cell tryptase formula, and specific IgE assays in anaphylaxis to neuromuscular blocking drugs. Using a score threshold of 15 or greater to indicate allergic perioperative immediate hypersensitivity reaction, the sensitivity was 88.9%, with a specificity of 79.4%. Prospectively, the Hypersensitivity Clinical Scoring Scheme correctly classified a greater number of subjects than the expert panel and the optimal post hoc binary logistic regression model (86% vs 85% vs 84%), however it was inferior to skin testing. ConclusionThe Hypersensitivity Clinical Scoring Scheme predicts allergic perioperative immediate hypersensitivity using features of the acute syndrome. This approach could guide algorithms for the post-resuscitative management of suspected perioperative immediate hypersensitivity, and identify patients requiring drug provocation challenge.

Anesthetic management of allergic hypersensitivity during a surgical procedure: A case report and literature review

Introduction: Perioperative anaphylaxis is a rare but serious, life-threatening condition that presents challenges in diagnosis and management. The incidence of severe perioperative reactions is estimated to be approximately 1:7,000–10,000. Case report: A 75-year-old patient underwent a surgical procedure due to adhesions of previous surgeries. She had a serious anaphylactic reaction in the intraoperative period, which was quickly addressed with fluid and adrenaline administration. Discussion: Proper management involves both immediate stabilization of the patient and identification of the causing agent. This identification is essential to avoid the recurrence of the event in other surgeries. A previous history of perioperative hypersensitivity reaction is the main risk factor for anaphylaxis.

Further Understanding of Neuro-Immune Interactions in Allergy: Implications in Pathophysiology and Role in Disease Progression.

The complicated interaction between the central and the autonomic (sympathetic, parasympathetic, and enteric) nervous systems on the one hand and the immune system and its components, on the other hand, seems to substantially contribute to allergy pathophysiology, uncovering an under-recognized association that could have diagnostic and therapeutic potentials. Neurons connect directly with and regulate the function of many immune cells, including mast cells, the cells that have a leading role in allergic disorders. Proinflammatory mediators such as cytokines, neurotrophins, chemokines, and neuropeptides are released by immune cells, which stimulate sensory neurons. The release of neurotransmitters and neuropeptides caused by the activation of these neurons directly impacts the functional activity of immune cells and vice versa, playing a decisive role in this communication. Successful application of Pavlovian conditioning in allergic disorders supports the existence of a psychoneuroimmunological interplay in classical allergic hypersensitivity reactions. Activation of neuronal homeostatic reflexes, like sneezing in allergic rhinitis, coughing in allergic asthma, and vomiting in food allergy, offers additional evidence of a neuroimmunological interaction that aims to maintain homeostasis. Dysregulation of this interaction may cause overstimulation of the immune system that will produce profound symptoms and exaggerated hemodynamic responses that will lead to severe allergic pathophysiological events, including anaphylaxis. In this article, we have systematically reviewed and discussed the evidence regarding the role of the neuro-immune interactions in common allergic clinical modalities like allergic rhinitis, chronic rhinosinusitis, allergic asthma, food allergy, atopic dermatitis, and urticaria. It is essential to understand unknown – to most of the immunology and allergy experts – neurological networks that not only physiologically cooperate with the immune system to regulate homeostasis but also pathogenetically interact with more or less known immunological pathways, contribute to what is known as neuroimmunological inflammation, and shift homeostasis to instability and disease clinical expression. This understanding will provide recognition of new allergic phenotypes/endotypes and directions to focus on specialized treatments, as the era of personalized patient-centered medicine, is hastening apace.

Food allergy testing in atopic dermatitis

Food allergy and food-related worsening of dermatitis can occur in patients with atopic dermatitis (AD). We reviewed the relationship of AD with food allergen hypersensitivity and the risks and benefits of food allergen testing and avoidance in patients with AD. Skin prick testing and specific immunoglobulin E to aeroallergens may identify patients with immediate hypersensitivity. Atopy patch tests may detect non–immunoglobulin E–mediated reactions but are not standardized or routinely used. Younger children with more severe AD in whom the optimal management failed may have food-triggered AD. Egg, milk, and peanut account for most food allergens. Elimination of relevant food allergens should improve AD but must be guided by appropriate allergy testing and establishing clinical relevance. Serum immunoglobulin E panels for food allergens are discouraged in the primary care setting because of their difficulty of interpretation. Empiric avoidance of foods is entirely discouraged in AD because of their risk of causing nutritional issues, food allergy, and other problems.

Rare Heterogeneous Adverse Events Associated with mRNA-Based COVID-19 Vaccines: A Systematic Review.

Background: Since the successful development, approval, and administration of vaccines against SARS-CoV-2, the causative agent of COVID-19, there have been reports in the published literature, passive surveillance systems, and other pharmacovigilance platforms of a broad spectrum of adverse events following COVID-19 vaccination. A comprehensive review of the more serious adverse events associated with the Pfizer-BioNTech and Moderna mRNA vaccines is warranted, given the massive number of vaccine doses administered worldwide and the novel mechanism of action of these mRNA vaccines in the healthcare industry. Methods: A systematic review of the literature was conducted to identify relevant studies that have reported mRNA COVID-19 vaccine-related adverse events. Results: Serious and severe adverse events following mRNA COVID-19 vaccinations are rare. While a definitive causal relationship was not established in most cases, important adverse events associated with post-vaccination included rare and non-fatal myocarditis and pericarditis in younger vaccine recipients, thrombocytopenia, neurological effects such as seizures and orofacial events, skin reactions, and allergic hypersensitivities. Conclusions: As a relatively new set of vaccines already administered to billions of people, COVID-19 mRNA-based vaccines are generally safe and efficacious. Further studies on long-term adverse events and other unpredictable reactions in close proximity to mRNA vaccination are required.

Allergic Contact Cell-Mediated Hypersensitivity in Psoriasis: A Narrative Minireview.

The dysfunctionality of the protective skin barrier in psoriasis allows easier cutaneous penetration of various contact haptens; thus, such patients can develop allergic contact hypersensitivity as a comorbidity. Both skin conditions involve T-cell-mediated mechanisms. Dermatologists and allergists should consider assessing allergic contact cell-mediated hypersensitivity in selected psoriasis patients, especially those with palmoplantar psoriasis and who are refractory to topical treatments, and in patients with psoriasis, with or without arthritis, treated with biologics that present skin lesions clinically suggestive of contact dermatitis.

Title-Inflammatory Signaling Pathways in Allergic and Infection-Associated Lung Diseases

Lung inflammation can be caused by pathogen infection alone or by allergic disease, leading to pneumonitis. Most of the allergens (antigens) that cause allergic lung diseases, including asthma and hypersensitivity pneumonitis (HP), are derived from microorganisms, such as bacteria, viruses, and fungi, but some inorganic materials, such as mercury, can also cause pneumonitis. Certain allergens, including food and pollen, can also cause acute allergic reactions and lead to lung inflammation in individuals predisposed to such reactions. Pattern recognition-associated and damage-associated signaling by these allergens can be critical in determining the type of hypersensitization and allergic disease, as well as the potential for fibrosis and irreversible lung damage. This review discusses the signs, symptoms, and etiology of allergic asthma, and HP. Furthermore, we review the immune response and signaling pathways involved in pneumonitis due to both microbial infection and allergic processes. We also discuss current and potential therapeutic interventions for infection-associated and allergic lung inflammation.

Anaphylaxis and pathophysiology

Anaphylaxis is the most severe of the allergic hypersensitivity reactions. It is caused by the release of mediators from blood components such as mast cells and basophils into the bloodstream. Anaphylaxis is a common disease, its diagnosis is clinical and, given its pathophysiology, the treatment of choice is adrenaline.