Development Of IgE Antibodies Research Articles

The Two-Sided Experimental Model of ImmunoCAP Inhibition Test as a Useful Tool for the Examination of Allergens Cross-Reactivity on the Example of α-Gal and Mammalian Meat Sensitization-A Preliminary Study.

Cross-reactivity of allergens is the cause of various, sometimes unexpected, clinical reactions. There are no standard methods to investigate cross-reactivity. We present an experimental model of a two-sided inhibition test (IT) on ImmunoCAP membranes (CAP). We constructed the described model based on the known cross-allergy syndrome to red meat developing in people bitten by ticks (α-Gal syndrome; AGS). Some individuals who are bitten by ticks develop IgE antibodies specific to the carbohydrate determinant, galactose-α-1,3-galactose (α-Gal), present in the tick's saliva. These antibodies can cross-react with α-Gal molecules expressed on mammalian meat proteins. The well-known property of anti-α-Gal IgE antibodies binding by various sources of this allergen was used by us in the proposed model of the two-sided inhibition test on ImmunoCAP membranes. We expected that anti-α-Gal IgE antibodies bind allergens from mammalian meat and blocking them abolishes this reactivity, and the two-sided inhibition test model we proposed on ImmunoCAP membranes allowed us to observe such a relationship. We conducted the experiment three times on biological material from people with different clinical manifestations of allergy to α-Gal, each time obtaining similar results. In conclusion, the model of bilateral inhibition on ImmunoCAP membranes proposed by us seems to be an attractive, simple tool for direct testing of allergic cross-reactivity.

IgE and mast cells in host defense against parasites and venoms.

IgE-dependent mast cell activation is a major effector mechanism underlying the pathology associated with allergic disorders. The most dramatic of these IgE-associated disorders is the fatal anaphylaxis which can occur in some people who have developed IgE antibodies to otherwise innocuous antigens, such as those contained in certain foods and medicines. Why would such a highly "maladaptive" immune response develop in evolution and be retained to the present day? Host defense against parasites has long been considered the only beneficial function that might be conferred by IgE and mast cells. However, recent studies have provided evidence that, in addition to participating in host resistance to certain parasites, mast cells and IgE are critical components of innate (mast cells) and adaptive (mast cells and IgE) immune responses that can enhance host defense against the toxicity of certain arthropod and animal venoms, including enhancing the survival of mice injected with such venoms. Yet, in some people, developing IgE antibodies to insect or snake venoms puts them at risk for having a potentially fatal anaphylactic reaction upon subsequent exposure to such venoms. Delineating the mechanisms underlying beneficial versus detrimental innate and adaptive immune responses associated with mast cell activation and IgE is likely to enhance our ability to identify potential therapeutic targets in such settings, not only for reducing the pathology associated with allergic disorders but perhaps also for enhancing immune protection against pathogens and animal venoms.

P-002 YI First Dose IgE-Mediated Allergy to Infliximab Due to Galactose-α-1,3-Galactose Allergy

Background:Mammalian meat allergy is an IgE antibody-mediated response to a mammalian oligosaccharide epitope galactose-α-1,3-galactose (alpha-gal). Anaphylaxis may occur after patients bitten by a lone star tick develop IgE antibodies to alpha-gal and are re-exposed to the same epitope following in

Anaphylactic Reaction After Beef Consumption Due to the Development of IgE Antibodies Against the Carbohydrate Galactose-Alpha-1,3-Galactos

Anaphylactic Reaction After Beef Consumption Due to the Development of IgE Antibodies Against the Carbohydrate Galactose-Alpha-1,3-Galactos

Atopy and Development of Cancer: A Population-Based Prospective Study

Atopy is the familial or personal propensity to develop IgE antibodies against environmental allergens. Atopy, theoretically, could both prevent and promote the development of cancer. However, evidence from epidemiologic studies has been inconclusive. We investigated the longitudinal association between atopy and the incidence of total and specific types of cancers of 5 Danish population-based studies. Atopy was defined as serum specific IgE positivity against inhalant allergens. A total of 14,849 persons were followed up prospectively by linkage to the Danish Cancer Registry. We used Cox regression analysis, and risk was expressed as hazard ratios (HR) (95% CIs) for persons with atopy versus those without atopy. There were 1919 incident cancers (median follow-up, 11.8 years). There were no statistically significant associations between atopy and risk of any cancer (HR 1.00 [95% CI, 0.89-1.12]), any cancer excluding nonmelanoma skin cancer (HR 0.93 [95% CI, 0.82-1.07]), head and neck cancer (HR 1.74 [95% CI, 0.98-3.09]), colorectal cancer (HR 0.92 [95% CI, 0.64-1.32]), cancer of the bronchus and lung (HR 0.78 [95% CI, 0.54-1.13]), breast cancer (HR 1.00 [95% CI, 0.73-1.37]), cancer of the uterus (HR 0.90 [95% CI, 0.43- 1.88]), prostate cancer (HR 0.79 [95% CI, 0.53-1.18]), urinary cancer (HR 1.08 [95% CI, 0.60-1.96]), malignant melanoma (HR 0.95 [95% CI, 0.54-1.66]), and nonmelanoma skin cancer (HR 1.20 [95% CI, 0.98-1.47]). Our data did not support the hypothesis that atopy is associated with an altered risk of total cancer development, although effects of atopy on specific types of cancer cannot be excluded.

IL-1 Family Cytokines Drive Th2 and Th17 Cells to Innocuous Airborne Antigens

Allergic asthma is commonly thought to result from dysregulated airway inflammatory responses to ubiquitous environmental antigens mediated by CD4(+) T cells polarized to a Th2 or Th17 cell. However, the mechanisms involved in the development of these T-cell responses remain unknown. This study examines the effects of IL-1 family cytokines, such as IL-33 and IL-1β, on the development of antigen-specific Th2 and Th17 cells in the airway. We administered IL-1 family cytokines and model antigens, such as ovalbumin, into the airways of naive BALB/c mice, and examined the cellular and humoral immune responses. To investigate the immunologic mechanisms, we used IL-4 green fluorescent protein reporter mice and mice deficient in the Il4 gene. Innocuous antigens, such as endotoxin-free ovalbumin and short ragweed extract, did not sensitize naive mice when administered through the airways. However, when mice were exposed to the same antigens with IL-1β or IL-33, they developed IgE antibodies. In particular, IL-33 induced robust and long-lasting Th2 cells that produced a large quantity of IL-5 and IL-13 and asthma-like airway pathology. IL-1β induced Th17 cells. In naive, nonsensitized animals, IL-33 stimulated endogenous IL-4 expression by CD4(+) T cells, which was critical for the polarization of CD4(+) T cells to the Th2 type. In the absence of IL-4, mice developed Th17 cells and neutrophilic airway inflammation. In conclusion, IL-1 family cytokines possess a potent adjuvant activity to promote both Th2 and Th17 cells to innocuous airborne antigens, and they may play fundamental roles in the immunopathology of asthma.

A Peculiar Cause of Anaphylaxis: No More steak?

In recent years, a newly recognized allergic disease has been uncovered, and seemingly idiopathic causes of anaphylaxis now have an explanation. Individuals bitten by the lone star tick may develop IgE antibodies to the carbohydrate galactose-α-1,3-galactose (alpha-gal). Upon exposure of sensitized subjects to mammalian meat containing alpha-gal on glycoproteins or glycolipids, delayed anaphylaxis may ensue, often three to six hours after ingestion.1 Many of these individuals have negative allergy skin prick tests to meat, further obscuring the diagnosis. With the recent development of IgE alpha-gal tests, the clinical diagnosis can be confirmed in the laboratory.

Enzyme replacement therapy in a patient with Fabry disease and the development of IgE antibodies against agalsidase beta but not agalsidase alpha

Fabry disease is an X-linked inherited lysosomal storage disorder caused by an inborn deficiency of the enzyme α-galactosidase A. Enzyme replacement therapy (ERT) with agalsidase alpha or beta isozymes is an effective treatment. Cross-reactivity of immunoglobulin G (IgG) antibodies with agalsidase alpha and beta has been reported, but no such reaction has been recorded for IgE antibodies. We present the case of a patient with Fabry disease who developed antiagalsidase beta IgE antibodies without cross-reactivity to agalsidase alpha. A 17-year-old boy with Fabry disease had suffered from severe atopic dermatitis since infancy, and he complained for several years of peripheral pain during the summer months and when exercising. Fabry disease was confirmed by family history and a positive enzyme test, and ERT was commenced. Following infusion of agalsidase beta (1.0 mg/kg), the patient complained of a high temperature in his hands and feet, and purulent eczema developed. The infusion dose was reduced to 0.2 mg/kg, but the hyperthermia did not change, although its duration decreased. After three infusions, eosinophilia developed (9.4%; 573 cells/μl blood) and remained unresolved after four infusions with agalsidase beta. Treatment with this enzyme was discontinued, and agalsidase alpha (0.2 mg/kg) started. This produced immediate resolution of the eosinophilia, which has been maintained during follow-up. In conclusion, this patient developed IgE antibodies against agalsidase beta, which demonstrated no cross-reactivity to agalsidase alpha. These findings emphasize the importance of analyzing IgE antibodies against both enzymes when patients exhibit severe infusion-related events.

Innovation in immunotherapy

Innovation in immunotherapy

Successful reinstitution of agalsidase beta therapy in Fabry disease patients with previous IgE-antibody or skin-test reactivity to the recombinant enzyme

PurposeTo determine if enzyme replacement therapy, involving intravenous infusions of recombinant human α-galactosidase A (agalsidase beta; Fabrazyme®), could be safely continued in patients with Fabry disease who had been withdrawn from a previous clinical trial as a precautionary, protocol-specified measure due to detection of serum IgE antibodies or skin-test reactivity to agalsidase beta. MethodsThe rechallenge infusion protocol specified strict patient monitoring conditions and graded dosing and infusion-rate schemes that were adjusted according to each patient's tolerance to the infusion. Six males (age: 26–66 years) were enrolled. ResultsDuring rechallenge, five patients received between 4 and 27 infusions; one patient voluntarily withdrew after one infusion because of recurrence of infusion-associated reactions. No anaphylactic reactions occurred. All adverse events, including four serious adverse events, were mild or moderate in intensity. Most treatment-related adverse events occurred during infusions (most commonly urticaria, vomiting, nausea, chills, pruritus, hypertension) and were resolved by infusion rate reductions and/or medication. After participation in the study, all patients, including the one who withdrew after one infusion, transitioned to commercial drug. ConclusionsAgalsidase beta therapy can be successfully reinstated in patients with Fabry disease who have developed IgE antibodies or skin test reactivity to the recombinant enzyme.

Affinity of IgE and IgG against cross-reactive carbohydrate determinants on plant and insect glycoproteins

Cross-reactive carbohydrate determinants (CCDs) are probably the most widely occurring IgE epitopes. Approximately one fifth of patients with allergy develop IgE antibodies against such glycans. However, they appear to be of low clinical significance. We wanted to elucidate the reasons for this lack of clinical symptoms on contact with CCD allergens by determination of the binding affinities of patients' IgE and IgG antibodies. IgE and IgG against CCDs were affinity-purified from sera of selected patients. The binding affinity to defined glyco-epitopes was measured by surface plasmon resonance. From a pool of CCD-positive sera, we isolated 0.1 and 25 microg CCD-specific IgE and IgG, respectively. The binding affinity of purified IgE antibodies to core alpha1,3-fucosylated glycans was in the 10(-10) mol/L range. The affinity was highest when both fucose and xylose were present, whereas xylosylation alone did not cause IgE binding. CCD-specific IgG exhibited a dissociation constant of approximately 10(-8) mol/L. IgG(4) amounted to only 20% of the CCD-specific IgG (as well as total IgG). Low binding affinity of anti-CCD IgE cannot be the reason for the observed clinical insignificance of IgE against plant/insect glycan epitopes. Notably, the affinity of IgG to CCDs is higher than that to protein allergens, and it may therefore function as blocking antibody.

Specificity of IgE antibodies to sequential epitopes of hen's egg ovomucoid as a marker for persistence of egg allergy

Approximately two-thirds of egg-allergic infants become tolerant within the first 5 years of life. We sought (1) to compare the recognition of sequential (linear) and conformational binding sites of ovomucoid, ovalbumin and ovotransferrin, by IgE antibodies of children with persistent and transient egg allergy, (2) to identify immunodominant IgE-and IgG-binding epitopes of ovomucoid, and (3) to compare epitope-specificity of IgE antibodies between patients with differing natural histories of egg allergy. Using immunodot-blots or ImmunoCAPs, IgE-antibodies against conformational (native) and sequential (reduced and alkylated) egg proteins were determined at the time of clinical reactivity in patients who retained their allergy and in those who developed clinical tolerance. IgE- and IgG-binding epitopes were mapped for ovomucoid using overlapping decapeptides on SPOTs membranes. Recognition of the major IgE-binding epitopes were compared between patients with differing natural histories of egg allergy. The patients with long-lasting egg allergy had a higher concentrations of IgE antibodies against sequential and native ovomucoid and ovalbumin than the children who subsequently gained tolerance (P < 0.01). Four major IgE-binding epitopes were identified in ovomucoid at amino acid 1-10, 9-20, 47-56, and 113-124. IgE antibodies of all seven patients with persistent egg allergy recognized these epitopes whereas none of the 11 children who outgrew their egg allergy did so. Patients with persistent egg allergy develop IgE antibodies against more sequential and conformational epitopes of ovomucoid and ovalbumin. The presence of serum IgE antibodies to specific sequential epitopes of ovomucoid may be used as a screening instrument for persistent egg allergy.

A prospective study of allergy development in 158 children and 128 adults with new extensive exposure to furred animals

There is still controversy over whether exposure to furred animals increases or decreases the risk of developing sensitization and allergic symptoms to such animals, and there is a need for further knowledge on this subject. The aim of this study was to follow allergy development in relation to new extensive exposure to furred animals in adults and children. A total of 286 individuals, 128 parents and 158 children, were recruited from 68 families who intended to buy a dog or a cat, or where one child of the family intended to start riding a horse. Subjects were examined before the new allergen exposure and once a year thereafter for 5 years, in all at six occasions, and they also completed questionnaires covering allergy symptoms. Serum IgE antibodies to cat, dog and horse were determined each year, and fur allergens from beds and living rooms were analysed. Two-hundred and fifty-six study subjects remained for evaluation, 37 of whom showed signs of allergic sensitization at the start of the study. Four children (11%) in this pre-sensitized group developed IgE antibodies to their new animal and six (16%) to another animal. Among the 219 participants who were not sensitized when entering the study, one male adult (0.4%) developed a sensitization to his new animal, and nobody developed sensitization to other animals. Pre-sensitized individuals had significantly more allergic symptoms at the study start, but the symptom scores did not change over time. When the first year of a human's life has passed, we have no strong evidence to recommend avoidance of a domestic animal in order to prevent new allergy development, even if there are known allergies in the family or if the individual is sensitized and has allergic symptoms to another allergen. Five years exposure to new fur allergens does not seem to influence sensitization to these animals in either sensitized or non-sensitized children and adults.

Hypersensitivity to airborne spitting cobra snake venom

Although the cytolytic, neurotoxic, and hemolytic actions of snake venoms are well known, the ability of airborne inhaled snake venom of the spitting cobra to induce asthma in snake handlers has not been reported. To report the allergenicity of inhaled snake venom in a snake handler who developed increasing hypersensitivity to airborne venom, produced by spitting cobras during public demonstrations. Serum samples were obtained from 2 handlers (our study patient and another snake handler who reported developing wheezing when handling spitting cobras), and desiccated venom was obtained from 9 species to which the handlers were exposed. Serum from an asymptomatic and nonatopic snake handler exposed to the same snake species was used as a control. Phosphate-buffered saline extracts were prepared from the desiccated venom, proteins in the venom extracts were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunoblotting was performed. Inhibition enzyme-linked immunosorbent assays (ELISAs) were performed to demonstrate cross-reactivity. The study patient had never been previously bitten by a cobra. Wheezing occurred rapidly on inhalational exposure and was reversed by inhalation of salbutamol. The patient had developed IgE antibodies to 9 different snake venoms on Western immunoblots, with major IgE binding proteins of 59 to 63 kDa and 8 to 15 kDa. The cross-reactive nature of the IgE epitopes in the venoms in the different species was also confirmed by 50% inhibition of IgE binding in an ELISA by preincubation with unrelated species. Life-threatening sensitivity of the patient was sustained after a long period of avoidance. We propose that aerosolized snake venom be considered a new potential source of allergens that may result in anaphylaxis on subsequent exposure. Further studies of the development of specific IgE sensitization following snakebites and the risks of such sensitization should be conducted on snake handlers, particularly those who demonstrate the spitting species.

108 Exposure to enzymes in detergents does not lead to the development of IgE antibody among consumers

108 Exposure to enzymes in detergents does not lead to the development of IgE antibody among consumers

109 Development of IgE antibody to enzymes in personal care products

109 Development of IgE antibody to enzymes in personal care products

The genetics of atopy and atopic eczema.

A genetic predisposition to the development of certain allergic diseases has been recognized since the early 1900s. In 1916, Cooke and van der Veer 1 reported that almost 50% of patients with allergic rhinitis and asthma had a positive family history of similar illness. In 1923, Coca and Cooke 2 coined the term atopy to describe immediate hypersensitivity reactions that had an inherited tendency. Their classification scheme was later criticized because of the mistaken belief that atopic diseases were transmitted in an autosomal dominant fashion. Coca and Cooke believed that reaginic (allergic) antibodies played a central role in disease pathogenesis, although they failed to recognize that these reactions were dependent on antigen-antibody interactions. Nonetheless, the term atopy has persisted in the medical literature and is often used synonymously with the terms allergy and immediate hypersensitivity. Consensus regarding a precise definition for atopy is lacking, 3,4 Since the discovery of IgE and the elucidation of the mechanisms involved in immediate-type hypersensitivity reactions, most authors use the term to describe the inherited tendency to develop IgE antibodies to specific allergens. The inherited tendency to produce allergen-specific IgE predisposes individuals to the development of certain diseases, including asthma, allergic rhinitis, and atopic dermatitis.

The application of phage display in allergy research: characterization of IgE, identification of allergens and development of novel therapeutics.

The ability to display IgE antibody fragments, allergens and peptides upon filamentous phage has increasingly been used in allergy research. This technique offers the opportunity to isolate and produce IgE antibody fragments specific for allergens. These antibody fragments can then be used to address fundamental issues regarding the development of IgE antibodies in allergic patients, at both the molecular and structural level. Random peptide display has greatly facilitated the discovery of epitopes recognized by serum IgE antibodies from allergic patients, and it is a definitive tool for investigating the IgE-epitope interaction. Whole allergens can also be displayed on phage. Selecting IgE binding phage from diverse cDNA libraries of allergens has assisted in the identification of new allergens and provided a source of purified allergens for the diagnosis of allergic diseases. Finally, phage display of antibody fragments and random peptides is currently providing a means by which the IgE antibody can be targeted as a potential treatment for allergy. This review highlights several studies which have utilized phage display methodology in the area of allergy research, and it discusses how the therapeutic potential of this approach may be exploited.

Allergy to Plant Seed Proteins

ABSTRACT Allergenicity is defined as the ability of proteins and other agents to sensitize genetically predisposed individuals to develop IgE antibodies, which bind to mast cells and basophils through the Fc portion of the IgE antibody. Upon subsequent exposures to the same protein, the proteins (allergens) bind to and cross-link cell bound IgE stimulating the release of mediators (histamine) that lead to an allergic reaction (Immediate Hypersensitivity). Seed proteins represent one important class of proteins that can induce a variety of allergic syndromes. Aerosolized particles released during pollination, harvest, transport and storage of grains and seed crops can cause inhalant allergy in susceptible individuals. Increased use of cereal grains, legumes and nuts in the diet has been suggested to contribute to the rise in the prevalence of food allergies. Plant biotechnology affords unique opportunities to identify individual components of seeds or seed products that may cause allergies and to remove or...

Mechanism and epidemiology of laboratory animal allergy.

Laboratory animal allergy (LAA) is a form of occupational allergic disease. The development of laboratory animal allergy is due to the presence of IgE antibodies directed against animal proteins. The process of sensitization (development of IgE antibodies) is a complex process which involves interaction of antigen presenting cells and lymphocytes of the Th-2 cell type. These cells generate a host of cytokines and other factors which lead to immediate hypersensitivity reactions and other factors which lead to immediate hypersensitivity reactions and the generation of allergic inflammation. Typical symptoms of laboratory animal allergy include nasal symptoms, such as sneezing, watery discharge, and congestion. Skin rashes are also common. Asthma, which produces symptoms of cough, wheezing, and shortness of breath, may affect 20-38% of workers who are sensitized to laboratory animal allergens. Rarely a generalized, life-threatening allergic reaction (anaphylaxis) may occur. The estimated prevalence of laboratory animal allergy is variable depending on the method used for diagnosis, but nonetheless may affect up to 46% of exposed workers. The presence of pre-existing allergies to non-work place allergens (e.g., dust mite, pollens, molds), exposure to laboratory animal allergens, and possibly tobacco smoking are risk factors for the development of laboratory animal allergy. Progress in the understanding of the mechanism and epidemiology of laboratory animal allergy will lead to improved methods for its prevention.