Production Of Specific IgE Antibodies Research Articles

Dissecting Airborne Allergens.

Asthma is a heterogeneous and very complex group of diseases, and includes different clinical phenotypes depending on symptoms, progression, exacerbation patterns, or responses to treatment, among other characteristics. The allergic phenotype is the most frequent, especially in pediatric asthma. It is characterized by sensitization (the production of specific IgEs) to allergens and frequent comorbidity with rhinitis as well as atopic dermatitis. Given the complexity of allergic asthma, knowledge of it must be approached from different points of view: clinical, histological, physiological, epidemiological, biochemical, and immunological, among others. Since partial approaches do not allow for the understanding of this complexity, it is necessary to have multidimensional knowledge that helps in performing the optimal management of each case, avoiding a "blind men and elephant parable" approach. Allergens are antigens that trigger the production of specific IgE antibodies in susceptible individuals, who present symptoms that will depend on the type and intensity of the allergenic load as well as the tissue where the interaction occurs. Airborne allergens cause their effects in the respiratory tract and eyes, and can be indoor or outdoor, perennial, or seasonal. Although allergens such as mites, pollens, or animal dander are generally considered single particles, it is important to note that they contain different molecules which could trigger distinct specific IgE molecules in different patients. General practitioners, pediatricians, and other physicians typically diagnose and treat asthma based on clinical and pulmonary function data in their daily practice. This nonsystematic and nonexhaustive revision aims to update other topics, especially those focused on airborne allergens, helping the diagnostic and therapeutic processes of allergic asthma and rhinitis.

Yer Fıstığında Bulunan Alerjenler ve Alerjen Etkiyi Azaltma Yöntemleri

Peanut allergens adversely affect the health and quality of life of millions of consumers worldwide. The seeds of the peanut plant (Arachis hypogaea L.) contain a number of allergens that trigger the production of specific IgE antibodies in allergy-prone individuals. Currently, 18 proteins found in peanuts are accepted as allergens. These allergens are named from Ara h 1 to Ara h 18. Ara h 2, Ara h 6 and Ara h 7 are from albumin, Ara h 1 and Ara h 3 are from globülin. Ara h is the abbreviation of Arachis hypogaea, the Latin name for peanut. A peanut allergy is a reaction that occurs shortly after eating to peanuts or peanut products. It has various symptoms that can go up to swelling of the tongue, itching of the palate, itching and burning in the throat, itching in the eyes and nose, nausea, vomiting, abdominal pain, shortness of breath, wheezing, bruising, chest pain, hives, low blood pressure and shock. In this review, the properties of peanut allergens and the methods of reducing the allergen effect will be reviewed.

Sensitisation and allergic reactions to alpha-1,3-galactose in Podlasie, Poland, an area endemic for tick-borne infections

Purpose Ticks transmit several pathogens and seem implicated in the production of specific IgE antibodies to alpha-1,3-galactose (α-gal sIgE). They cause delayed and immediate allergy to mammalian meat and medication including antivenoms, vaccines and monoclonal antibodies. Methods We assessed the prevalence of α-gal sIgE in forest workers and healthy controls in the Podlasie voivodeship, north-eastern Poland; the relationship between α-gal sIgE and allergy to α-gal-containing products; the correlation between α-gal sIgE and anti-Borrelia burgdorferi and anti-tick-borne encephalitis virus (TBEV) antibodies; the relationship between α-gal sIgE and markers of infection with lesser-known pathogens transmitted by ticks such as Anaplasma phagocytophilum. Results Production of α-gal sIgE was closely related to tick bites. The odds ratio for detectable α-gal sIgE was 9.31 times higher among people with a history of tick bites (OR 9.3; p < .05). There was no correlation with the history of TBE, Lyme disease or human granulocytic anaplasmosis. However, serum α-gal sIgE correlated with anti-TBEV IgM antibodies in CSF. There was a strong correlation between α-gal sIgE and total IgE and sIgE to pork and beef. Conclusions Our data support the link between I.ricinus ticks and the production of α-gal sIgE and confirm that the pathogens carried by ticks we examined for do not seem implicated in this immune response.

Place of residence, gender, month of birth and age influence on the concentration of specific IgE antibodies in serum. The Epidemiology of Allergic Diseases in Poland (ECAP survey): part three.

IntroductionSpecific immunoglobulins E (sIgE) are important parameters to estimate the severity of allergic diseases.AimTo determine the influence of gender, age and place of residence on the concentration of specific IgE antibodies in serum.Material and methodsThe concentration of sIgE antibodies against allergens of Dermatophagoides pteronyssinus, cat dander, timothy grass, Alternaria alternata were determined in serum of 4077 respondents randomly selected from 8 regions (ECAP study). The positive results of sIgE (≥ 0.35 IU/ml) were correlated with answers to ECAP questionnaires.ResultsIgE antibodies are less frequently detected in respondents living in the country (p < 0.05 to p < 0.005); and they are less frequently detected in respondents living in cities of hardly industrialised regions than in respondents living in cities of industrialised regions (D. pteronyssinus p < 0.05, cat dander p < 0.01). IgE antibodies are more frequently detected in men (p < 0.005 to p < 0.001). IgE antibodies are more frequently detected in respondents born in May-July (timothy grass p < 0.005, Alternaria alternata p < 0.005) and less frequently detected in respondents born in August-October (timothy grass p < 0.005, Alternaria alternata p < 0.05).ConclusionsCharacteristics of the urban environment, non-specific factors and gender affect the concentration of specific IgE antibodies in serum. Influence of seasonal allergens within the first months of life and/or in the course of the foetal period alters the production of specific IgE antibodies.

Peanut allergens

Peanut allergens have the potential to negatively impact on the health and quality of life of millions of consumers worldwide. The seeds of the peanut plant Arachis hypogaea contain an array of allergens that are able to induce the production of specific IgE antibodies in predisposed individuals. A lot of effort has been focused on obtaining the sequences and structures of these allergens due to the high health risk they represent. At present, 16 proteins present in peanuts are officially recognized as allergens. Research has also focused on their in-depth immunological characterization as well as on the design of modified hypoallergenic derivatives for potential use in clinical studies and the formulation of strategies for immunotherapy. Detailed research protocols are available for the purification of natural allergens as well as their recombinant production in bacterial, yeast, insect, and algal cells. Purified allergen molecules are now routinely used in diagnostic multiplex protein arrays for the detection of the presence of allergen-specific IgE. This review gives an overview on the wealth of knowledge that is available on individual peanut allergens.

Detection of the mecA gene in Staphylococcus sp. isolated from dog skin with atopic dermatitis and recurrent pyoderma

Canine atopic dermatitis (CAD) is a multifactorial, allergic and inflammatory skin disorder with a genetic predisposition manifested by clinical signs, and it is generally associated with the production of specific IgE antibodies, mainly against environmental allergens. The objective of this study was to report the occurrence of mecA gene in an isolate of Staphylococcus sp. from a dog with canine atopic dermatitis and recurrent pyoderma. Clinical specimen was collected for culture and antimicrobial susceptibility analysis. The isolate of Staphylococcus was then submitted to PCR for the detection of the mecA gene. The isolation of Staphylococcus sp. from this patient’s skin is worrisome, since the presence of such multi-resistant bacterium in such circumstance is a potentially grave risk for public health.

The Role of Malassezia spp. in Atopic Dermatitis.

Malassezia spp. is a genus of lipophilic yeasts and comprises the most common fungi on healthy human skin. Despite its role as a commensal on healthy human skin, Malassezia spp. is attributed a pathogenic role in atopic dermatitis. The mechanisms by which Malassezia spp. may contribute to the pathogenesis of atopic dermatitis are not fully understood. Here, we review the latest findings on the pathogenetic role of Malassezia spp. in atopic dermatitis (AD). For example, Malassezia spp. produces a variety of immunogenic proteins that elicit the production of specific IgE antibodies and may induce the release of pro-inflammatory cytokines. In addition, Malassezia spp. induces auto-reactive T cells that cross-react between fungal proteins and their human counterparts. These mechanisms contribute to skin inflammation in atopic dermatitis and therefore influence the course of this disorder. Finally, we discuss the possible benefit of an anti-Malassezia spp. treatment in patients with atopic dermatitis.

Local IgE in non-allergic rhinitis.

Local allergic rhinitis (LAR) is characterized by the presence of a nasal Th2 inflammatory response with local production of specific IgE antibodies and a positive response to a nasal allergen provocation test (NAPT) without evidence of systemic atopy. The prevalence has been shown to be up to 25% in subjects affected with rhinitis with persistence, comorbidity and evolution similar to allergic rhinitis. LAR is a consistent entity that does not evolve to allergic rhinitis with systemic atopy over time although patients have significant impairment in quality of life and increase in the severity of nasal symptoms over time. Lower airways can be also involved. The diagnosis of LAR is based mostly on demonstration of positive response to NAPT and/or local synthesis of specific IgE. Allergens involved include seasonal or perennial such as house dusts mites, pollens, animal epithelia, moulds (alternaria) and others. Basophils from peripheral blood may be activated by the involved allergens suggesting the spill over of locally synthesized specific IgE to the circulation. LAR patients will benefit from the same treatment as allergic patients using antihistamines, inhaled corticosteroids and IgE antagonists. Studies on immunotherapy are ongoing and will determine its efficacy in LAR in terms of symptoms improvement and evolution of the natural course of the disease.

Skin‐testing protocol in diagnosing of the IgE‐mediated peanut allergy

Background In the event that a food-allergen was presumed as a likely accused of signs/symptoms, after that, the substantiation of major associations and finally, identifying the incriminated food(s) need to be warranted. As for verifying of an IgE-mediated food allergy, different specific mensurations should be accomplished in order to include/exclude the suspected food(s). One protocol for meticulous interpretation −concerning the production of specific IgE-antibodies− is the accepted/endorsed prickpuncture skin-testing. Of note, Skin-Prick-Tests (SPTs) are referred to as authentic predicting-value in cases where they become negative (over 95 %).

Cutaneous or Respiratory Exposures to Peanut Allergens in Mice and Their Impacts on Subsequent Oral Exposure

Background: Recent data suggested that non-gastrointestinal exposure can lead to sensitisation to food allergens. We thus assessed the immune impact of respiratory or cutaneous exposure to peanut proteins on non-altered epithelium and investigated the effect of such pre-exposure on subsequent oral administration of peanut. Methods: BALB/cJ mice were exposed to purified Ara h 1 or to a non-defatted roasted peanut extract (PE) by simple deposit of allergens solutions on non-altered skin or in the nostrils. Exposures were performed 6 times at weekly intervals. Pre-exposed mice then received intra-gastric administrations of PE alone or in the presence of the Th2 mucosal adjuvant cholera toxin (CT). The specific humoral and cellular immune response was assessed throughout the protocol. Results: Both cutaneous and respiratory exposures led to the production of specific IgG1. Local and systemic IL-5 and IL-13 production were also evidenced, demonstrating activation of specific Th2 cells. This effect was dose-dependent and most efficient via the respiratory route. Moreover, these pre-exposures led to the production of specific IgE antibodies after gavage with PE, whatever the presence of CT. Conclusions: Cutaneous or respiratory exposures to peanut induce Th2 priming in mice. Moreover, pre-exposures promote further sensitisation via the oral route without the use of CT; this proposes a new adjuvant-free experimental model of sensitisation to food that may reflect a realistic exposure pattern in infants. These results also suggest that non-gastrointestinal peanut exposure should be minimised in high-risk infants, even those with non-altered skin, to potentially reduce allergic sensitisation to this major food allergen.

Characterization of the allergenic potential of proteins: an assessment of the kiwifruit allergen actinidin

Assessment of the potential allergenicity (IgE-inducing properties) of novel proteins is an important challenge in the overall safety assessment of foods. Resistance to digestion with pepsin is commonly measured to characterize allergenicity, although the association is not absolute. We have previously shown that specific IgE antibody production induced by systemic [intraperitoneal (i.p.)] exposure of BALB/c strain mice to a range of proteins correlates with allergenic potential for known allergens. The purpose of the present study was to explore further the utility of these approaches using the food allergen, actinidin. Recently, kiwifruit has become an important allergenic foodstuff, coincident with its increased consumption, particularly as a weaning food. The ability of the kiwifruit allergen actinidin to stimulate antibody responses has been compared with the reference allergen ovalbumin, and with the non-allergen bovine haemoglobin. Haemoglobin was rapidly digested by pepsin whereas actinidin was resistant unless subjected to prior chemical reduction (reflecting intracellular digestion conditions). Haemoglobin stimulated detectable IgG antibody production at relatively high doses (10%), but failed to provoke detectable IgE. In contrast, actinidin was both immunogenic and allergenic at relatively low doses (0.25% to 1%). Vigorous IgG and IgG1 antibody and high titre IgE antibody responses were recorded, similar to those provoked by ovalbumin. Thus, actinidin displays a marked ability to provoke IgE, consistent with allergenic potential. These data provide further encouragement that in tandem with analysis of pepsin stability, the induction of IgE after systemic exposure of BALB/c strain mice provides a useful approach for the prospective identification of protein allergens.

Relation curares et pholcodine

Allergic reactions to neuromuscular blocking agents (NMBAs) are in most cases IgE-mediated. Ammonium-substituted ions have been identified as the allergenic epitope, NMBAs being bivalent for this epitope. A large number of allergic reactions occur in the absence of prior exposure to an NMBA, supporting the hypothesis of cross-sensitization resulting from prior exposure to environmental substances which have ammonium-substituted ions. Several recent clinical reports suggest a possible role for pholcodine, a cough-suppressing morphine derivative containing two different allergenic epitopes. Pholcodine could play a role either through direct sensitization or through a booster effect on the production of specific IgE antibodies. Its withdrawal from the market appears to have resulted in a significant decrease in the number of allergic reactions to NMBAs in Norway and Sweden. Nevertheless, a recent decision of the European Medicine Agency (EMA) concluded that the level of proof was insufficient to require that this drug be withdrawn from the European market. However, the EMA strongly recommended that additional clinical studies are urgently needed to allow further evaluation of the possible association between exposure to pholcodine and sensitization to NMBAs. Such studies appear to be essential.

Nasal allergen provocation test with multiple aeroallergens detects polysensitization in local allergic rhinitis

Patients previously given a diagnosis of nonallergic rhinitis (NAR) might have a new form of local allergic rhinitis (LAR) with local production of specific IgE antibodies and a positive response to a nasal allergen provocation test (NAPT). We evaluated an NAPT protocol using multiple aeroallergens (NAPT-M) for the detection of polysensitization to several aeroallergens in patients with LAR. NAPT-Ms with 2 different panels of aeroallergens for patients with perennial and seasonal rhinitis were performed in 25 patients with LAR and 25 patients with NAR whose disease was diagnosed by means of NAPTs 1 year earlier. The response to nasal challenge was evaluated based on subjective (nasal-ocular symptoms) and objective (acoustic rhinometry) parameters. Nasal levels of tryptase and eosinophil cationic protein were determined by means of immunoassay at baseline, 15 minutes, and 1, 2, and 24 hours after challenge. NAPT-Ms showed 100% concordance with the gold standard of NAPTs with a single aeroallergen. No false-positive or false-negative responses were detected. The use of NAPT-Ms achieved 75% reduction in the total number of visits required for final diagnosis in the NAR group (from 168 to 42 visits) and a 55% reduction in the LAR group (from 144 to 65 visits) compared with NAPTs with a single aeroallergen. These results demonstrate that clinically relevant polysensitization to aeroallergens in patients with LAR occurred and that the NAPT-M is a useful, specific, sensitive, reproducible, and less time-consuming invivo diagnostic test for the screening of patients with LAR.

Factors Influencing the Allergenicity and Adjuvanticity of Allergens

IgE-mediated allergic disorders affect up to 25% of the population in industrialized countries and result in a Th2-polarized immune response to innocuous environmental proteins, so-called allergens. Among a large number of proteins to which humans are exposed to, only a minute fraction are allergens. This observation suggests that allergens share special features of allergenicity (i.e., the capacity to induce the production of specific IgE antibodies in susceptible individuals). However, the question 'what makes a protein allergenic' still remains unanswered although some biochemical characteristics of allergens and their capacity to interact with the innate immune system could be associated with their allergenic potential. Allergen-specific immunotherapy aims at an alteration of the disease-eliciting immune response by repeated administration of allergens. Recently, approaches emerged to endow allergens with adjuvanticity, in particular aiming at an increase of their immunomodulatory capacity. This article summarizes factors of allergenicity and introduces recent concepts of adjuvanticity to improve allergen-specific immunotherapy.

Local allergic rhinitis: Allergen tolerance and immunologic changes after preseasonal immunotherapy with grass pollen

Local allergic rhinitis: Allergen tolerance and immunologic changes after preseasonal immunotherapy with grass pollen

Molecular allergology approach to allergic diseases in the paediatric age.

Identification, characterization, and purification of allergens are essential for the structural and immunologic studies needed to understand how these molecules induce specific IgE antibody production by the human immune system. Advances in molecular biology techniques have led to the production of recombinant allergens having constant properties, allowing detection of specific IgE directed against different molecular components of an allergenic source. Presence of homologous allergens in different sources is the reason for cross-reaction. Molecule-based diagnostic tools can lead to better interpretation of poly-sensitizations, observed by ST and in vitro tests using allergenic extracts as they were made before. Some examples IgE sensitization to major genuine allergens and panallergens will be presented.

Mouse Monoclonal Immunoglobulin E Antibodies Specific for the MicrosporidianEncephalitozoon cuniculiPolar Tube Protein 1

The microsporidian Encephalitozoon cuniculi is a spore-forming, obligate, intracellular parasitic pathogen with a unique organelle called a polar tube, the extrusion of which is essential for invading a host cell. The polar tube consists of three proteins: polar tube protein 1 (PTP1), PTP2, and PTP3. We established three mouse monoclonal antibodies (MAb1, MAb2, and MAb4) against E. cuniculi PTP1. An enzyme-linked immunosorbent assay (ELISA) indicated that all three MAbs reacted with the outer surface of extruded polar tubes and that they also strongly bound to an intracellular antigen in infected host cells. Two-dimensional (2-D) immunoblot analysis showed that MAb1 and MAb2 recognized PTP1 spots at 52 kDa and some spotty smears at molecular weights of less than 50 kDa, whereas MAb4 recognized only PTP1 spots at 52 kDa. Interestingly, all three MAbs were of the immunoglobulin (Ig) E class, suggesting that, in addition to the highly immunogenic or antigenic nature, the PTP1 antigen may have the potential to induce specific IgE antibody production in mice. These antibodies may be useful in the study of allergenic PTP1 as well in the purification and detection of the PTP1 antigen.

The many faces of the hygiene hypothesis

About 15 years have gone by since Strachan first proposed the idea that infections and unhygienic contact might confer protection against the development of allergic illnesses. The so-called hygiene hypothesis has ever since undergone numerous more or less subtle modifications by various researchers in the fields of epidemiology, clinical science, and immunology. Three major tracts have developed exploring the role of overt viral and bacterial infections, the significance of environmental exposure to microbial compounds, and the effect of both on underlying responses of the innate and adaptive immunity. To date, a truly unifying concept has not yet emerged, but various pieces of a complex interplay between immune responses of the host, characteristics of the invading microorganism, the level and variety of the environmental exposure, and the interactions between a genetic background and a range of exposures becomes apparent. These influences are discussed as determinants for a number of complex allergic illnesses in this review, while we attempt to pay attention to the importance of different phenotypes, namely of the asthma syndrome. Even if today practical implications cannot directly be deduced from these findings, there is great potential for the development of novel preventive and therapeutic strategies in the future.

IgE Production after Four Routes of Injections of Japanese Cedar Pollen Allergen without Adjuvant: Crucial Role of Resident Cells at Intraperitoneal or Intranasal Injection Site in the Production of Specific IgE toward the Allergen

The production of specific IgE antibodies directed toward cedar pollen correlates well with the onset of allergic rhinitis; but the mechanisms of allergen recognition as nonself and Ig class switch to IgE by the immune system are still not fully understood. In the present study, we injected cedar pollen into mice through 4 different routes (intranasal (i.n.), intraperitoneal (i.p.), intravenous (i.v.), and subcutaneous (s.c.)) without adjuvant 1 to 3 times, and determined time-dependent changes in the total and specific serum IgE levels compared with those in the serum levels of other isotype Igs. After an i.p. or i.n. injection of allergen into the mice, they produced a 1.5-to 1.7-fold increase in total IgE, but none in IgG, IgM, or IgA antibodies in their serum, whereas an i.v. or s.c. injection of allergen was inactive as an inducer of total IgE antibodies. Upon a 2nd (s.c.) injection of the allergen into the i.p. or i.n. sensitized mice, a large amount of allergen-specific IgE antibodies was found in the serum. In the case of i.v. or s.c. sensitized mice, however, they produced total, but not specific, IgE antibodies; and a 3rd (s.c.) injection of the allergen resulted in a large amount of specific IgE antibodies in the serum. These results imply that resident cells at the i.p. or i.n. injection site may play a crucial role in the efficient production of total and specific IgE antibodies toward the allergen.

Specific serum IgE levels and FcɛRIβ genetic polymorphism in patients with penicillins allergy

Numerous studies have suggested that both genetic and environmental influences are involved in the pathogenesis of allergic disease and atopy. The objective of this investigation is to elucidate the underlying mechanism of penicillins allergy and improve the diagnostic methods. Radioallergosorbent test was used to examine eight kinds of specific IgE antibodies, which included four kinds of major and minor antigenic determinants, respectively, in the sera of 448 patients with penicillins allergy and 101 healthy subjects. A restriction endonuclease fragment length polymorphism of a polymerase chain reaction product was used for analysis of the FcepsilonRIbeta polymorphism. The positive rate of specific IgE in 448 patients was 58.26% (261), in which 37.28% (167) patients had positive IgE to major antigenic determinants and 47.09% (211) patients had positive IgE to minor antigenic determinants. Of the 179 patients with allergic history, 70.83% (17/24) patients had positive antibodies within 30 days, while 45.28% (24/53) had positive antibodies after 5 years. The positive reaction degree of skin test was absolutely correlated with specific IgE (P=0.047). Among patients with positive specific IgE, significant differences of E237G genotype were observed between patients with positive benzylpenicillanyl (BPA)-, phenoxomethylpenicilloyl (PVO)- or ampicilloyl (APO)-IgE and control group (P=0.015, 0.015, and 0.008, respectively). There were significant differences in E237G genotype between positive and negative BPA-, PVO- as well as APO-IgE patients (P = 0.014, 0.02, and 0.011, respectively). The patients with penicillins allergy have positive specific IgE not only to major antigenic determinants but also to minor antigenic determinants. The E237G variant of the FcepsilonRIbeta gene is involved in the development of penicillins allergy through the process for the production of specific IgE antibodies.