Immediate Hypersensitivity Research Articles

Rhinovirus upregulates transient receptor potential channels in a human neuronal cell line: implications for respiratory virus-induced cough reflex sensitivity

BackgroundThe mechanism underlying respiratory virus-induced cough hypersensitivity is unknown. Upregulation of airway neuronal receptors responsible for sensing physical and chemical stimuli is one possibility, and the transient receptor potential (TRP)...

Occupational Exposure to Particulate Matter and Respiratory Symptoms in Portuguese Swine Barn Workers

Certain environmental conditions in animal and plant production have been associated with increased frequency in respiratory illnesses, including asthma, chronic bronchitis, and hypersensitivity pneumonitis, in farmers occupationally exposed in swine production. The aim of this study was to characterize particulate matter (PM) contamination in seven Portuguese swine farms and determine the existence of clinical symptoms associated with asthma and other allergy diseases, utilizing the European Community Respiratory Health Survey questionnaire. Environmental assessments were performed with portable direct-reading equipment, and PM contamination including five different sizes (PM0.5, PM1.0, PM2.5, PM5.0, PM10) was determined. The distribution of particle size showed the same trend in all swine farms, with high concentrations of particles with PM5 and PM10. Results from the questionnaire indicated a trend such that subjects with diagnosis of asthma were exposed to higher concentrations of PM with larger size (PM2.5, PM5, and PM10) while subjects with sneezing, runny nose, or stuffy nose without a cold or flu were exposed to higher concentrations of PM with smaller size (PM0.5 and PM1). Data indicate that inhalation of PM in swine farm workers is associated with increased frequency of respiratory illnesses.

Oral administration of chitin and chitosan prevents peanut-induced anaphylaxis in a murine food allergy model

Peanut allergy is IgE-mediated type-I hypersensitivity, and T helper 2 cytokines are central to those pathogenesis. We investigated the effects of the administration of chitin and chitosan on peanut-induced hypersensitivities in mouse food allergy models. Chitin and chitosan protected mice against peanut-induced anaphylaxis reactions, and the peanut-specific IgE production decreased by up to 47% with the administration of β-chitosan. The levels of IL-5, IL-13, and IL-10 were significantly suppressed in all groups (α-chitin≥β-chitin≥β-chitosan). These results suggested that the administration of chitin and chitosan from by-products of food processing are beneficial for the prevention of food allergies.

Biomarkers for non-human primate Type-I hypersensitivity: Antigen-specific immunoglobulin E assays

Immunoglobulin E (IgE) is the least abundant immunoglobulin in serum. However, development of an IgE immune response can induce IgE receptor-expressing cells to carry out potent effector functions. A reliable antigen-specific IgE biomarker method for use in non-human primate studies would facilitate (i) confirmation of Type-I hypersensitivity reactions during safety toxicology testing, and (ii) a better understanding of non-human primate models of allergic disease. We cloned and expressed a recombinant cynomolgus monkey IgE molecule in order to screen a panel of commercially available detection reagents raised against human IgE for cross-reactivity. The reagent most reactive to cynomolgus IgE was confirmed to be specific for IgE and did not bind recombinant cynomolgus monkey IgG1-4. A drug-specific IgE assay was developed on the MSD electrochemiluminescent (ECL) platform. The assay is capable of detecting 10ng/mL drug-specific IgE. Importantly, the assay is able to detect IgE in the presence of excess IgG, the scenario likely to be present in a safety toxicology study. Using our ECL assay, we were able to confirm that serum from cynomolgus monkeys that had experienced clinical symptoms consistent with hypersensitivity responses contained IgE specific for a candidate therapeutic antibody. In addition, a bioassay for mast cell activation was developed using CD34+-derived cynomolgus monkey mast cells. This assay confirmed that plasma from animals identified as positive in the drug-specific IgE immunoassay contained biologically active IgE (i.e. could sensitize cultured mast cells), resulting in histamine release after exposure to the therapeutic antibody. These sensitive assays for Type-I hypersensitivity in the NHP can confirm that secondary events are downstream of immunogenicity.

Effects of propofol on airway hyperresponsiveness and airway inflammation of asthmatic mice

Objective To investigate the immunoregulatory effects of propofol on airway hyperresponsiveness,airway inflammation and Thl/Th2 ratio in the asthmatic mice.Methods One hundred female BALB/c mice,aged 6-8 weeks,weighing 18-20 g,were randomly divided into 5 groups (n =20,each):control group (normal saline i.p.,group C),asthma group (group A),low-dose propofol (50 mg/kg i.p.,group LP),medium-dose propofol (100 mg/kg i.p.,group MP) and high-dose propofol (150 mg/kg i.p.,group HP).Mice of groups A,LP,MP and HP were sensitized with ovalbumin (OVA),mice of group C were sensitized with normal saline.24 h after the last challenge,animals were sacrificed by lethal dose of pentobarbital sodium.Blood and bronchoalveolar lavage fluid (BALF) were collected for determination of serum OVA-specific IgE and the levels of cytokines (IL-4,IL-5 and IFN-γ) in the BALF.Airway responsiveness was measured by the forced-oscillation technique and histological inflammation scores were measured by staining with hematoxylin and eosin.Results Propofol (group LP and group MP) attenuated airway hyperresposiveness to the muscarinic agonist methacholine in OVA-induced asthma.Different doses of propofol (group LP,group MP and group HP) decreased eosinoplils influx in lungs.In addition,propofol treatment reduced expression of IL-4,IL-5 and serum OVA-specific IgE and increased the ratio of IFN-γ/IL-4.Conclusion The study demonstrates a potential protective value of propofol in alleviating airway inflammation,up-regulating Th1/Th2 ratio and attenuating airway hyperresposiveness in the asthmatic mice. Key words: Asthma; Propofol ; Respiratory hypersensitivity ; Inflammation

Immediate hypersensitivity to platelet concentrate: allergic or not?

Immediate hypersensitivity to platelet concentrate: allergic or not?

Characterization of aspirin allergies in patients with coronary artery disease

BackgroundAspirin prevents coronary thrombosis and is used extensively in cardiovascular prophylaxis. However, patients with a prior history of an aspirin “reaction” are routinely denied this medication. ObjectiveTo characterize the clinical presentation of a cohort of patients with coronary artery disease (CAD) and aspirin reactions. MethodsBetween 2009 and 2012, using a retrospective computer analysis, information was collected on all patients within a county-wide health care system presenting with CAD and a prior history of aspirin reactions. ResultsOf 9,565 patients with CAD, a prior history of aspirin reactions was recorded in 142 patients. Of these 142 patients, 30 (21%) had histories compatible with cutaneous and/or respiratory reactions. The other patients described adverse effects to aspirin, mostly gastrointestinal intolerance and bleeding. Aspirin-induced anaphylaxis was recorded in patients but may have been misdiagnosed, describing instead respiratory hypersensitivity reactions. Of the 142 patients, only 34 (24%) were receiving daily cardiovascular prophylaxis with aspirin. Of 108 patients not receiving aspirin, 25 (17.6%) were prescribed clopidogrel. ConclusionHistories of aspirin reactions in patients with CAD are uncommon, occurring in only 1.5% of our study population. The 21% of patients with histories compatible with aspirin hypersensitivities can be challenged and, if the results are positive, successfully desensitized. Moreover, almost all patients with gastric intolerance to aspirin can be treated with aspirin and a proton pump inhibitor. However, both approaches, which result in restoration of cardiovascular prophylaxis, were seriously underused in our study population.

Kiwifruit as a food allergen source

Since its first appearance on the market kiwifruit has become very popular in the human diet due to its pleasant taste, low caloric value and high content of vitamin C. However, kiwifruit allergy has become a frequent cause of type I hypersensitivity in the western society. Molecular basis for kiwifruit allergy has been ascribed to up-to-now 11 identified IgE reactive molecules. They are proteins and glycoproteins with a molecular mass between 50 and 10 kDa. The major kiwifruit allergen is a cysteine protease denoted as Act d 1, which represents 50% of the soluble protein extract. Due to a difference in the abundance of protein components and biological activity, the quality of kiwifruit extracts intended for allergy diagnosis can vary in content and amount of IgE reactive molecules. In addition, the quality of allergen extracts for allergy diagnosis depends on the fruit ripening stage and storage conditions. In terms of clinical reactivity it has become evident that kiwifruit allergy is not a homogeneous disorder. Different patterns of IgE reactivity accompany several clinical subgroups that have been identified in different geographical regions. In the last decade an enormous progress has been made in isolation and characterization of kiwifruit allergens. This paper will give an overview of the structural features of kiwifruit allergens.

Zotarolimus-eluting stent-induced hypersensitivity pneumonitis

Zotarolimus-eluting stent-induced hypersensitivity pneumonitis

Establishment of a method to quantify the specific IgE against sweat antigen in sera of patients with atopic dermatitis

Background: Sweat is a major aggravating factor of atopic dermatitis (AD) and approximately 80% of patients with AD reveal type I-hypersensitivity against sweat and semi-purified sweat antigen (QRX). To diagnose the sweat allergy, we routinely perform the basophil histamine release test (HRT). However, HRT needs fresh blood cells of patients and its results are qualitative rather than quantitative. In this study, to overcome the disadvantages of HRT, we established the enzyme-linked immunosorbent assay (ELISA) to measure specific IgE against sweat antigen by using sera of patients with AD.

Latex allergy in health care.

The increasing use of natural rubber latex medical gloves in the last three decades has caused an increase in latex allergy. The majority of risk groups for allergy development include health care workers, workers in the rubber industry, atopic individuals and children with congenital malformations. Three types of pathological reactions can occur in people using latex medical gloves: irritant contact dermatitis, allergic contact dermatitis and immediate hypersensitivity. The latex allergy is caused by constituent components of latex gloves and added powders; there are also numerous latex allergens involved in cross-reactivity between latex and fruits and vegetables, the so-called latex-fruit syndrome. The diagnosis is based on an accurate history of exposure, clinical presentation and confirmatory in vivo and in vitro tests. Prevention is the easiest, most effective and least expensive way to avoid latex allergy. Powder-free latex gloves with reduced levels of proteins and chemicals, and synthetic gloves for allergic workers must be provided in the work environment. There are already many health care institutions around the world where all latex products have been replaced by synthetic material products.

CɛmX peptide-carrying HBcAg virus-like particles induced antibodies that down-regulate mIgE-B lymphocytes

Type-I hypersensitivity reactions play a critical role in the pathogenesis of various allergic diseases. The successful development of the anti-IgE antibody, omalizumab, has validated IgE as an effective therapeutic target for the treatment of various IgE-mediated allergic diseases. Two research groups have reported that mAbs specific for certain parts of CɛmX, a domain of 52 aa residues in human membrane-bound IgE (mIgE), can cause the lysis of mIgE-B cells by apoptosis and antibody-dependent cellular cytotoxicity (ADCC). Herein, we explore virus-like particles formed by hepatitis B virus core antigen (HBcAg) that harbors the entire CɛmX peptide or its fragments as immunogens for inducing anti-CɛmX antibodies. The results showed that mice immunized subcutaneously with these immunogens produced antibodies that bind to recombinant CɛmX-containing human IgE.Fc in ELISA and Western blot analyses, and to genetically engineered human mIgE-expressing Ramos B cell line in fluorescence flow cytometric assays. The IgG antibodies purified from the sera of immunized mice were able to cause the apoptosis of mIgE-expressing Ramos cells through a BCR-dependent caspase pathway. Furthermore, the IgG could mediate ADCC in human mIgE-expressing A20 murine B-cell lymphoma. These studies suggest that HBcAg-CɛmX peptide immunogens warrant further investigation as a therapeutic modality for modulating IgE in patients with IgE-mediated allergic diseases.

Antibiotic-Associated Eosinophilic and Occlusive Arteritis in Calves Complicating Preclinical Studies of Left Ventricular Assist Devices

Repeated bolus intravenous (IV) administration of large doses of beta-lactams and aminoglycosides has previously been associated with the development of eosinophilic and occlusive arterial lesions limited to the lungs in calves. Reviewing 13 years worth of records from left ventricular assist device implantation studies, morphologically identical segmental arterial lesions were present in 32 of the 56 calves receiving IV antibiotics, affecting lungs (6/50), kidneys (12/56), or lungs and kidneys (14/50). In 16 of these calves, renal arterial lesions spatially colocalized with renal cortical infarctions. Lesions were noted in additional abdominal organs in 4 of the 50 calves and were exclusively present in the liver in a single calf. Similar arterial lesions were also noted in the lungs (3/4), kidneys (1/4), liver (1/4), and spleen (1/4) of unimplanted calves receiving similar IV antibiotic regimens for bacterial infections. Lesions were observed with therapeutic IV doses of cephalosporins with or without aminoglycosides over shorter intervals than previously implicated. Lesions were significantly associated with increased peripheral eosinophil counts and mildly elevated, not reduced, arterial pulse pressures. This report documents the features of an idiosyncratic drug reaction with features strongly suggestive of an acute type-I hypersensitivity in this species.

Mechanism of walnut induced anaphylaxis-like shock reaction in mice (175.1)

Abstract Walnut is a leading cause of life-threatening anaphylaxis in humans. Such reactions are largely thought to be mediated by the Type-I hypersensitivity mechanism. We have found that English walnut extract (EWE) upon oral or i.p., administration in naive mice without pre-sensitization results in anaphylaxis-like shock response as quantified by hypothermia. We have been studying the mechanism underlying this unusual reaction. The Fcg receptor knockout (KO) mice, IgE non-responder SJL mice and TLR4 mutant C3H/HeJ mice, all exhibited hypothermia response indicating that the reaction was antibody and LPS independent respectively. We then examined the role of complement system. The C3a receptor (C3aR) KO mice were protected from shock responses. Among the C5 deficient (DBA/1J) and C5 sufficient (DBA/2J) mice, both exhibited hypothermia responses with DBA1 being a slightly lower responder. Since the shock reaction was complement dependent, we reasoned and tested whether EWE causes hemagglutination (HA) of RBC. Using a standard HA assay protocol we evaluated the HA activity of EWE. We found that the EWE had a significant HA activity for RBC obtained from BALB/c, DBA/1J and DBA/2J mice (HA titre: 1/32; translates to ~35,555 HA units per gram of EWE protein). These data are consistent with the hypothesis that EWE causes HA in vivo leading to complement system activation with consequent C3aR dependent anaphylaxis-like shock reaction.

Complexity of case mix in a regional allergy service

BackgroundCurrently in the United Kingdom (UK), there is a mismatch between limited financial resources and the large proportion of patients with suspected allergies actually being referred to specialist allergy clinics. To better understand the case mix of patients being referred, we audited referrals to a regional allergy service over an 8 year period.The main source of data was consultant letters to General Practitioners (GP) summarising the diagnosis of patients, archived from January 2002 to September 2009. Letters were reviewed, extracting the clinic date, doctor seen, gender, date of birth, postcode, GP, and diagnoses. Diagnoses were classified into seven groups and illustrative cases for each group noted.FindingsData from 2,028 new referrals with suspected allergy were analysed. The largest group of patients (43%) were diagnosed with a type I hypersensitivity. The other diagnostic groups were chronic idiopathic (spontaneous) urticaria (35%), suspected type I hypersensitivity but no allergen identified (8%), idiopathic (spontaneous) angioedema (8%), physical urticaria (2.5%), non-allergic symptoms (1.6%), type IV hypersensitivity (0.8%) and ACE inhibitor sensitivity (0.5%). Two thirds of patients seen were female with a higher percentage of female patients in the non type-I hypersensitivity group (71%) than the type 1 hypersensitivity (66%) (χ2 = 5.1, 1df, p = 0.024). The type 1 hypersensitivity patients were younger than other patients (38 Vs 46 years, t = -10.8, p < 0.001)ConclusionsThis study highlights the complexity of specialist allergy practice and the large proportion of patients referred with non-type I hypersensitivities, chronic idiopathic (spontaneous) urticaria being by far the largest group. Such information is critical to inform commissioning decisions, define referral pathways and in primary care education.

Immunotherapy Monitoring Through Liposomes-An Altered Form of Bio-Sensing

Allergic reactions are caused by allergens belongs to the category of type-I hypersensitivity. The systemic release of histamine as a result of allergic reaction can be fatal anaphylaxis, creating a necessity to improve the efficiency of the treatment that is rendered to patients suffering from this hyper-sensitivity. The generally administered drugs include anti-histamine drugs, steroids and other oral medications but these drugs neutralizes the molecules released after the pseudo-infection, but not the misconception exercised by the immune system and only a temporary relief is achieved. An alternative is allergen immunotherapy, in which the patient is treated with a large dosage of the allergens leading to hyposensitization to the allergens. However anaphylaxis may happen. Hence, monitoring this treatment is vital. In this paper, the methodology of immunotherapy monitoring is given. The monitoring is carried out by liposomes that are made to carry address tags-monoclonal antibodies. The liposomes envelop the histamine molecules, which are emitted on reaching target site and designed in such a way that they emit fluorescence on enveloping histamine. Increased histamine secretion (higher amount of fluorescence) denotes the inefficacy of the treatment and suppressed levels denote otherwise, hence can be used as an online biosensor. This paper deals with subsequent monitoring of the same, thereby avoiding further complications.

Immediate allergic reaction to methylprednisolone with tolerance of other corticosteroids

In spite of the wide usage of corticosteroids for the treatment of a plethora of diseases, sometimes they can induce immediate hypersensitivity reactions, which are however uncommon. We report a case of immediate allergic reaction induced by intravenous methylprednisolone given before operation for surgical repair of an arm contracture as a sequel of burns, which the child had tolerated a month before. Six weeks later the patient repeated the anaphylactic reaction during skin testing to methylprednisolone. In addition, basophile activation test with methylprednisolone (BAT) was positive. This case report describes a patient who experienced intraoperative anaphylaxis and anaphylactic reaction induced by skin testing. This is the first report on induction of both anaphylactic reactions by methylprednisolone in the same child. Clinical findings, positive BAT and positive skin tests with methylprednisolone imply that the child developed type-I hypersensitivity. The lack of crossreactivity with other corticosteroids emphasizes that the reactions were caused by the steroid molecule.

Immunological Response to Parthenium hysterophorus in Indian Patients with Parthenium Sensitive Atopic Dermatitis

Parthenium hysterophorus is the leading cause of airborne contact dermatitis, a type IV hypersensitivity reaction in India. Though there are reports of it causing type-I hypersensitivity in atopic individuals in the form of allergic rhinitis and asthma, there is very little information on its role in pathogenesis of atopic dermatitis (AD), another predominately type I hypersensitivity. In the present study, we evaluated the presence of immediate hypersensitivity to P. hysterophorus in patients with AD and evaluated the in vitro immunological response of P. hysterophorus SPT positive AD patients to stimulation with P hysterophorus allergen. In 70 patients (age 15–45 years) with AD and 70 healthy controls, who were patch test negative to P. hysterophorus, immediate hypersensitivity to P hysterophorus was determined by skin prick test (SPT). In SPT positive patients with AD and SPT negative controls, the absolute eosinophil count (AEC), the total serum IgE and Parthenium specific IgE were determined and PBMC proliferation assay to Parthenium pollen using tritiated thymidine incorporation was done. The IL-4, IL-10, IL-2 and IFN-γ from stimulated PBMCs culture supernatant was also quantified using sandwich ELISA in both groups of patients. Twenty-five (35.7%) of 70 patients with AD had a positive SPT to Parthenium, compared to 3 (4.3%) of controls. The mean AEC, the mean total IgE and Parthenium specific IgE were significantly elevated in SPT positive AD patients vis-à-vis SPT negative controls. Similarly in the Parthenium specific PBMCs proliferation assay, the stimulation index as well as the Th2 cytokine (IL-4 and IL-10) profile were significantly elevated in SPT positive AD patients vis-à-vis SPT negative controls but there was no difference in the Th1 cytokine (IL-2 and IFN-γ) profile. Our study suggests that a third of patients with AD demonstrated a type I hypersensitivity to P. hysterophorus with a Th2 biased cytokine profile (IL-4 and IL-10) in culture supernatant of Parthenium stimulated PBMCs in these patients.

A study on the immunological basis of the dissociation between type I-hypersensitivity skin reactions to Blomia tropicalis antigens and serum anti-B. tropicalis IgE antibodies

BackgroundTwo conditions are used as markers of atopy: the presence of circulating anti-allergen IgE antibodies and the presence of positive skin prick test (SPT) reactions to allergenic extracts. The correlation between these conditions is not absolute. This study aimed at investigating immunological parameters that may mediate this lack of correlation. Individuals whose sera contained anti-B. tropicalis extract IgE antibodies (α-BtE IgE) were divided into two groups, according to the presence or absence of skin reactivity to B. tropicalis extract (BtE). The following parameters were investigated: total IgE levels; α-BtE IgE levels; an arbitrary α-BtE IgE/total IgE ratio; the proportion of carbohydrate-reactive α-BtE IgE; the proportion of α-BtE IgE that reacted with Ascaris lumbricoides extract (AlE); the production of IL-10 by BtE- and AlE-stimulated peripheral blood cells (PBMC).ResultsTotal IgE levels were similar in the two groups, but α-BtE IgE was significantly higher in the SPT-positive group (SPT+). A large overlap of α-BtE IgE levels was found in individuals of both groups, indicating that these levels alone cannot account for the differences in SPT outcome. Individuals of the two groups did not differ, statistically, in the proportion of α-BtE IgE that reacted with carbohydrate and in the production of IL-10 by BtE- and AlE-stimulated PBMC. Both groups had part of α-BtE IgE activity absorbed out by AlE, indicating the existence of cross-reactive IgE antibodies. However, the α-BtE IgE from the SPT-negative individuals (SPT-) was more absorbed with AlE than the α-BtE IgE from the SPT+ individuals. This finding may be ascribed to avidity differences of the α-BtE IgE that is present in the two groups of individuals, and could occur if at least part of the α-BtE IgE from the SPT- individuals were elicited by A. lumbricoides infection.ConclusionThe present results suggest that a low ratio of specific IgE to total IgE levels (in a minority of individuals), and differences in α-BtE IgE avidities (which would have high affinities for A. lumbricoides antigens in SPT- than in SPT+ individuals) may play a role in the down-modulation of type-I hypersensitivity reaction against aeroallergens described in helminth-infected individuals.

Do low testosterone levels contribute to the pathogenesis of asthma?

Asthma is a chronic inflammatory airway disorder that causes respiratory hypersensitivity and intermittent obstruction. Airway hyperresponsiveness to both specific and nonspecific stimuli is the hallmark of asthma. Although genetic susceptibility and airway inflammation are believed to play fundamental roles, etiology of asthma is unknown. In most cases, the treatment of asthma focuses on control of factors contributing to asthma severity and pharmacologic therapy including bronchodilator and anti-inflammatory agents. The prevalence of reported asthma is greater in prepubertal boys, with a change to a female predominance after puberty. Many epidemiological studies also suggest that women are at increased risk of developing adult-onset asthma and also suffer from more severe disease than men. This strongly suggests an important role for sex hormones in asthma. Previous articles provided us that, testosterone and/or its metabolites maintain the physiological balance of autoimmunity and protective immunity by preserving the number of regulatory cells. Testosterone is an immunosuppressant and is likely to be protective against immunological and inflammatory processes that trigger asthma. We hypothesized that the testosterone or selective androgen receptor modulators would have beneficial effects on asthma and could decrease the risk of asthmatic attacks.