Occupational asthma and IgE sensitization to grain dust.

PubMed Central

Park, H. S.; Nahm, D. H.; Suh, C. H.; Kwon, O. Y.; Kim, K. S.; Lee, S. W.; Chung, H. K.

1998-01-01

To evaluate type I hypersensitivity to grain dust (GD), its prevalence and relationship to respiratory dysfunction, we studied clinical and immunologic features, including skin prick tests (SPT), serum specific IgE, and bronchoprovocation tests of 43 employees working in the animal feed industry. To further characterize IgE-mediated reaction, SDS-PAGE and electroblot studies were performed. Our survey revealed that 15 (34.9%) subjects had work-related skin response (> or =2+ of A/H ratio) to GD, thirteen (30.2%) had high specific IgE antibody against GD. The specific IgE antibody was detected more frequently in symptomatic workers (40%) than in asymptomatic workers (11%). Significant association was found between specific IgE antibody and atopy or smoking (p<0.05). The ELISA inhibition test of GD revealed significant inhibitions by GD extract and minimal inhibitions by the house dust mite, storage mite and corn dust. Immunoblot analysis showed 8 IgE binding components within GD ranging from 13.5 to 142.5 kDa. Two bands (13.5, 33 kDa) were bound to the IgE from more than 50% of the 14 sera tested. In conclusion, these findings suggest that GD inhalation could induce IgE-mediated bronchoconstriction in exposed workers. PMID:9681805

Occupational asthma and IgE sensitization to grain dust.

PubMed

Park, H S; Nahm, D H; Suh, C H; Kwon, O Y; Kim, K S; Lee, S W; Chung, H K

1998-06-01

To evaluate type I hypersensitivity to grain dust (GD), its prevalence and relationship to respiratory dysfunction, we studied clinical and immunologic features, including skin prick tests (SPT), serum specific IgE, and bronchoprovocation tests of 43 employees working in the animal feed industry. To further characterize IgE-mediated reaction, SDS-PAGE and electroblot studies were performed. Our survey revealed that 15 (34.9%) subjects had work-related skin response (> or =2+ of A/H ratio) to GD, thirteen (30.2%) had high specific IgE antibody against GD. The specific IgE antibody was detected more frequently in symptomatic workers (40%) than in asymptomatic workers (11%). Significant association was found between specific IgE antibody and atopy or smoking (p<0.05). The ELISA inhibition test of GD revealed significant inhibitions by GD extract and minimal inhibitions by the house dust mite, storage mite and corn dust. Immunoblot analysis showed 8 IgE binding components within GD ranging from 13.5 to 142.5 kDa. Two bands (13.5, 33 kDa) were bound to the IgE from more than 50% of the 14 sera tested. In conclusion, these findings suggest that GD inhalation could induce IgE-mediated bronchoconstriction in exposed workers.

IgG1 memory B cells keep the memory of IgE responses.

PubMed

He, Jin-Shu; Subramaniam, Sharrada; Narang, Vipin; Srinivasan, Kandhadayar; Saunders, Sean P; Carbajo, Daniel; Wen-Shan, Tsao; Hidayah Hamadee, Nur; Lum, Josephine; Lee, Andrea; Chen, Jinmiao; Poidinger, Michael; Zolezzi, Francesca; Lafaille, Juan J; Curotto de Lafaille, Maria A

2017-09-21

The unique differentiation of IgE cells suggests unconventional mechanisms of IgE memory. IgE germinal centre cells are transient, most IgE cells are plasma cells, and high affinity IgE is produced by the switching of IgG1 cells to IgE. Here we investigate the function of subsets of IgG1 memory B cells in IgE production and find that two subsets of IgG1 memory B cells, CD80 + CD73 + and CD80 - CD73 - , contribute distinctively to the repertoires of high affinity pathogenic IgE and low affinity non-pathogenic IgE. Furthermore, repertoire analysis indicates that high affinity IgE and IgG1 plasma cells differentiate from rare CD80 + CD73 + high affinity memory clones without undergoing further mutagenesis. By identifying the cellular origin of high affinity IgE and the clonal selection of high affinity memory B cells into the plasma cell fate, our findings provide fundamental insights into the pathogenesis of allergies, and on the mechanisms of antibody production in memory B cell responses.IgE is an important mediator of protective immunity as well as allergic reaction, but how high affinity IgE antibodies are produced in memory responses is not clear. Here the authors show that IgE can be generated via class-switch recombination in IgG1 memory B cells without additional somatic hypermutation.

Impaired protection against Trichinella spiralis in mice with high levels of IgE.

PubMed

Watanabe, Naohiro

2014-04-01

Helminth infection induces production of a large amount of immunoglobulin E (IgE) to nonhelminth antigens. Although such "irrelevant" IgE is a major proportion of total IgE in the host, its biological significance remains unclear. Therefore, I examined protective activity against Trichinella spiralis in mice with high levels of IgE by repeated injections of anti-dansyl IgE monoclonal antibody or Nippostrongylus brasiliensis infection. Injected anti-dansyl IgE occupied IgE receptors on mast cells in naive mice. Protective activity against T. spiralis, determined with number of muscle larvae 5weeks after infection, was impaired in mice treated with anti-dansyl IgE. The impaired protection was found in mice treated with anti-dansy IgE 7 and 14days after infection, but not 21 and 28days after infection, indicating that IgE-dependent protection operates at an early stage after infection. In the next experiments, mice were infected with N. brasiliensis 4weeks before T. spiralis infection to obtain high levels of IgE. The protective activity against T. spiralis was decreased by N. brasiliensis infection. On the other hand, protection against T. spiralis was comparable in IgE-deficient SJA/9 mice and in anti-IgE-treated BALB/c mice with or without N. brasiliensis infection, suggesting that impairment of protection is dependent on IgE. These results indicate that the high levels of irrelevant IgE are beneficial for helminths and, alternatively, that anti-helminth IgE antibodies are protective for hosts. In addition, the impaired protection was found in IgE high-responder mice but not in low-responder mice, suggesting that protection against T. spiralis is controlled by IgE responsiveness in the host. Copyright © 2013 Elsevier B.V. All rights reserved.

IgE in lupus pathogenesis: Friends or foes?

PubMed

Augusto, Jean-François; Truchetet, Marie-Elise; Charles, Nicolas; Blanco, Patrick; Richez, Christophe

2018-04-01

Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving multiple immunological pathways. Recently, several studies have suggested an implication of Immunoglobulin E (IgE) in the pathophysiology of SLE. In the Lyn -/- and FcγIIB -/- .Yaa lupus mouse models, autoreactive IgE activate basophils, and promote a Th2 environment with, subsequently, production of autoantibodies by plasma cells. Autoreactive IgE has been also shown to play a role in the activation of human plasmacytoid dendritic cells (pDCs), in synergy with IgG, which results in an increase of interferon-alpha (IFN-α) production. In contrast, a protective effect of total non-autoreactive IgE has also been suggested, through a decreased ability of FcεRI-triggered pDCs to secrete IFN-α. This review summarizes in a comprehensive manner the emerging recent literature in the field, and propose new concepts to reconcile the observations. Copyright © 2018 Elsevier B.V. All rights reserved.

Serum IgE levels are associated with coronary artery disease severity.

PubMed

Guo, Xiaoxiao; Yuan, Su; Liu, Yongtai; Zeng, Yong; Xie, Hongzhi; Liu, Zhenyu; Zhang, Shuyang; Fang, Quan; Wang, Jing; Shen, Zhujun

2016-08-01

Immunoglobulin E (IgE), a key element of allergic reactions, was considered to be involved in the development of atherosclerosis and the pathogenesis of myocardial ischemia. This study was designed to test whether total serum IgE levels were associated with the atherosclerosis severity of coronary artery disease (CAD). Total serum IgE concentrations were measured in 708 consecutive patients who were presented to our center for coronary angiography. Atherosclerosis severity of CAD was assessed by the number of diseased vessels showing ≥50% diameter stenosis and quantified by Gensini score. Patients with CAD (N = 562) had higher serum IgE levels than those without CAD (N = 146) [55.90 (19.10-156.00) vs. 26.90 (11.80-62.10) KU/L, p = 0.003]. Furthermore, the serum IgE levels were significantly increased in patients with multivessel disease (MVD) compared to those with single-vessel disease [61.80 (23.20-159.00) vs. 32.45(14.15-94.38) KU/L, p = 0.003]. After adjustment for traditional cardiovascular risk factors, a high serum IgE level was an independent predictor for an increased risk of MVD (OR 1.003; 95% CI 1.001-1.004; p = 0.041). Receiver-operating characteristic curve analysis demonstrated that serum IgE levels improved the predictive capability of traditional risk factors for MVD (area under the curve with and without IgE: 0.734 and 0.713, respectively, p < 0.001). Meanwhile, there was a significant linear relationship between Gensini score and the serum IgE level quartiles (p for linear trend <0.001). Increased total serum IgE levels are associated with MVD and contribute to discriminating CAD severity independently of traditional cardiovascular risk factors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Maternal allergy is associated with surface-bound IgE on cord blood basophils.

PubMed

Matson, Adam P; Cloutier, Michelle M; Dhongade, Ashish; Puddington, Lynn; Rafti, Ektor

2013-09-01

The cell type(s) mediating the maternal influence on allergic disease in children remain unclear. We set out to define the relationship between maternal allergy and frequencies of cord blood (CB) basophils, and plasmacytoid dendritic cells (pDCs); to characterize surface-bound IgE and FcεRI expressions on these cells; and to investigate the association between maternal and CB serum IgE levels with surface-bound IgE and FcεRI expressions. One hundred and three mother/infant dyads were recruited prenatally, and maternal allergic history was recorded. Maternal blood was collected prior to delivery, and CB was collected after birth. Flow cytometry was used to identify CB basophils and pDCs and to determine surface-bound IgE and FcεRI expressions. Frequencies of CB basophils and pDCs were low and not related to maternal history of allergy. Percentages of CB basophils with surface-bound IgE were significantly higher in infants of allergic mothers compared with infants of non-allergic mothers (median, 59.60% vs. 19.70%, p = 0.01). IgE on CB basophils correlated with CB IgE levels (r = 0.72, p < 0.0001), but not with maternal IgE levels (r = 0.26, p = 0.06). IgE on CB pDCs was low and not significantly associated with maternal or CB IgE levels. Similarly, FcεRI expression by CB basophils and pDCs was not significantly associated with maternal or CB IgE levels. Frequencies of CB basophils and pDCs are not influenced by maternal allergy. CB basophils and pDCs have surface-bound IgE and express FcεRI; however, only IgE on CB basophils appears influenced by maternal allergy. © 2013 The Authors. Pediatric Allergy and Immunology published by John Wiley & Sons Ltd.

Approaches to target IgE antibodies in allergic diseases.

PubMed

Balbino, Bianca; Conde, Eva; Marichal, Thomas; Starkl, Philipp; Reber, Laurent L

2018-06-15

IgE is the antibody isotype found at the lowest concentration in the circulation. However IgE can undeniably play an important role in mediating allergic reactions; best exemplified by the clinical benefits of anti-IgE monoclonal antibody (omalizumab) therapy for some allergic diseases. This review will describe our current understanding of the interactions between IgE and its main receptors FcεRI and CD23 (FcεRII). We will review the known and potential functions of IgE in health and disease: in particular, its detrimental roles in allergic diseases and chronic spontaneous urticaria, and its protective functions in host defense against parasites and venoms. Finally, we will present an overview of the drugs that are in clinical development or have therapeutic potential for IgE-mediated allergic diseases. Copyright © 2018. Published by Elsevier Inc.

IGES, a key interface specification for CAD/CAM systems integration

NASA Technical Reports Server (NTRS)

Smith, B. M.; Wellington, J.

1984-01-01

The Initial Graphics Exchange Specification (IGES) program has focused the efforts of 52 companies on the development and documentation of a means of graphics data base exchange among present day CAD/CAM systems. The project's brief history has seen the evolution of the Specification into preliminary industrial usage marked by public demonstrations of vendor capability, mandatory requests in procurement actions, and a formalization into an American National Standard in September 1981. Recent events have demonstrated intersystem data exchange among seven vendor systems with a total of 30 vendors committing to offer IGES capability. A full range of documentation supports the IGES project and the recently approved IGES Version 2.0 of the Specification.

[Factors modifying cord blood IgE levels - a pilot study].

PubMed

Petrovičová, O; Bánovčin, P; Babušíková, E; Jeseňák, M

The complex influence of internal and external environmental factors on the individual and his/her immune system and the lack of suitable markers to assess and reduce the risk of the development of allergies during the lifetime can explain the continuous increase in the number of people affected by some form of allergy. According to the results of some studies, cord blood IgE level could be a useful early marker for assessing the risk of atopic diseases, but the studies showed controversial results. In addition, several authors discuss the origin of these antibodies (synthesis in utero, peripartum contamination from maternal blood or placental transfer). The aim of our pilot study was to investigate the possible influence of modifying factors on cord blood IgE level. Our group of patients consisted of 184 retrospectively selected neonates (98 boys, 53.3% and 86 girls, 46.7%) from whom cord blood was collected and cord blood IgE level was measured 25 years ago (PRIST method). The impact of selected modifying factors (sex, type of delivery or month of birth) on cord blood IgE level was assessed retrospectively. Higher cord blood IgE levels were found in boys than in girls, in neonates born by Caesarean section than in those born by natural delivery, and in those born in the winter months than in other seasons of the year. Our findings are in agreement with those of other authors. Based on our results and those of others, we assume that the selected factors affect the cord blood IgE levels to varying degrees. These facts should be taken into consideration while interpreting the cord blood IgE levels.

Individually Guided Education (IGE) Program. 1973-1974 Evaluation Report.

ERIC Educational Resources Information Center

Austin Independent School District, TX. Office of Research and Evaluation.

This report presents data gathered during the 1973-74 school year on the Austin Independent School District (Austin, Texas) implementation of the Individually Guided Education Program (IGE). Classroom observation indicates on the whole that the 11 schools identified as IGE exhibit greater degrees of implementation of characteristics associated…

[A VALIDATION STUDY OF THE IMPROVED PRODUCT FOR MEASURING JAPANESE CYPRESS POLLEN-SPECIFIC IgE (THERMO SCIENTIFIC™ ImmunoCAP™ ImmunoCAP JAPANESE CYPRESS POLLEN-SPECIFIC IgE)].

PubMed

Yonekura, Syuji; Okamoto, Yoshitaka; Nakayama, Satoshi

Japanese cypress pollen is a major causative allergen of seasonal allergic rhinitis in Japan. Although ImmunoCAP-specific immunoglobulin E (IgE) reagent Japanese cypress pollen has been widely used as a diagnostic aid, its sensitivity requires enhancement. This study evaluated an improved version of this reagent. Serum samples from 61 subjects who underwent Japanese cypress pollen exposure testing in an environmental challenge chamber in Chiba University were assessed using the conventional ImmunoCAPspecific IgE Japanese cypress pollen product and the improved product. In addition, specific IgE for Cha o 1 and Cha o 2, the primary allergen components of Japanese cypress pollen, was evaluated and their reactivity to specific IgE was compared between the conventional and improved products. The antibody titer of the improved product was approximately 1.8-fold that of the conventional product. In addition, higher correlations with Cha o 1 and Cha o 2 were observed for the improved product than for the conventional product. The clinical sensitivity (≥class 2) in 56 exposure test-positive subjects was better for the improved product (80.4%) than for the conventional product (71.4%). An improvement of the ImmunoCAP-specific IgE reagent Japanese cypress pollen resulted in enhanced Japanese cypress pollen-specific IgE sensitivity. The primary reason for this appeared to be an improved Cha o 1- and Cha o 2-specific IgE detectability.

Effect on IgE production of transplanted cultured thymic fragments.

PubMed Central

Nishikawa, M; Hong, R

1987-01-01

The effect of cultured thymic fragment (CTF) transplantation on the IgE response of nude mice was studied. Nude mice (BALB/c nu/nu) were immunized with a mixture of tetanus toxoid and aluminium gel intraperitoneally. Non-CTF transplanted nude mice could not regulate IgE production nor synthesize specific IgE antibody, and all died at 16 weeks of age. Nude mice that were transplanted with CTF from allogeneic low responder strains (C57BL/6, SJL), allogeneic high responder strain (ASW) and syngeneic high responder strain (BALB/c) could regulate IgE production, and these lived a normal life span. Additionally, the tetanus toxoid-specific IgE antibody response, which was estimated by PCA, paralleled that seen in the strain of the thymus donor, i.e. BALB/c and ASW thymus reconstitution produced the highest response, whereas SJL and C57BL/6 recipients' levels were significantly less (P less than 0.05). We postulate that the lesser responses were due to the determination of the phenotype response by the thymic microenvironment. The low responses were shown to be due to regulator T-cell imbalance. These data show that BALB/c T-cell precursors developing in non-BALB/c thymuses interact with BALB/c B cells to produce levels of IgE antibody that are more characteristic of the non-BALB/c differentiating microenvironment than of their own genetic background. PMID:3493208

IgE reactivity to hen egg white allergens in dogs with cutaneous adverse food reactions.

PubMed

Shimakura, Hidekatsu; Uchiyama, Jumpei; Saito, Taku; Miyaji, Kazuki; Fujimura, Masato; Masuda, Kenichi; Okamoto, Noriaki; DeBoer, Douglas J; Sakaguchi, Masahiro

2016-09-01

Dogs with cutaneous adverse food reactions (CAFR) often have specific IgE to food allergens. Egg white, which is majorly composed of ovomucoid, ovalbumin, ovotransferrin, and lysozyme, is a food allergen in dogs. Information of the IgE reactivity to purified egg white allergens supports accurate diagnosis and efficiency treatment in humans. However, to the best of our knowledge, there have been no studies on the IgE reactivity to purified egg white allergens in dogs. Here, we investigated the IgE reactivity to crude and purified allergens of hen egg white in dogs with CAFR. First, when we examined serum samples from 82 dogs with CAFR for specific IgE to crude egg white by ELISA, 9.8% (8/82) of the dogs with CAFR showed the IgE reactivity to crude egg white. We then used sera from the eight dogs with positive IgE reactivity to crude egg white to examine the IgE reactivity to four purified allergens, ovomucoid, ovalbumin, ovotransferrin, and lysozyme, by ELISA. We found that 75% (6/8) of the dogs showed IgE reactivity to both ovomucoid and ovalbumin, and that 37.5% (3/8) of the dogs showed IgE reactivity to ovotransferrin. None (0/8) showed IgE reactivity to lysozyme. Moreover, validating these results, the immunoblot analyses were performed using the sera of the three dogs showing the highest IgE reactivity to crude egg white. Both anti-ovomucoid and anti-ovalbumin IgE were detected in the sera of these dogs, while anti-ovotransferrin IgE was not detected. Considering these, ovomucoid and ovalbumin appears to be the major egg white allergens in dogs with CAFR. Copyright © 2016 Elsevier B.V. All rights reserved.

Microarray-based IgE detection in tears of patients with vernal keratoconjunctivitis.

PubMed

Leonardi, Andrea; Borghesan, Franco; Faggian, Diego; Plebani, Mario

2015-11-01

A specific allergen sensitization can be demonstrated in approximately half of the vernal keratoconjunctivitis (VKC) patients by conventional allergic tests. The measurement of specific IgE in tears using a multiplex allergen microarray may offer advantages to identify local sensitization to a specific allergen. In spring-summer 2011, serum and tears samples were collected from 10 active VKC patients (three females, seven males) and 10 age-matched normal subjects. Skin prick test, symptoms score and full ophthalmological examination were performed. Specific serum and tear IgE were assayed using ImmunoCAP ISAC, a microarray containing 103 components derived from 47 allergens. Normal subjects resulted negative for the presence of specific IgE both in serum and in tears. Of the 10 VKC patients, six resulted positive to specific IgE in serum and/or tears. In three of these six patients, specific IgE was found positive only in tears. Cross-reactivity between specific markers was found in three patients. Grass, tree, mites, animal but also food allergen-specific IgE were found in tears. Conjunctival provocation test performed out of season confirmed the specific local conjunctival reactivity. Multiple specific IgE measurements with single protein allergens using a microarray technique in tear samples are a useful, simple and non-invasive diagnostic tool. ImmunoCAP ISAC detects allergen sensitization at component level and adds important information by defining both cross- and co-sensitization to a large variety of allergen molecules. The presence of specific IgE only in tears of VKC patients reinforces the concept of possible local sensitization. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

IgE Immunoadsorption Knocks Down the Risk of Food-Related Anaphylaxis.

PubMed

Dahdah, Lamia; Ceccarelli, Stefano; Amendola, Silvia; Campagnano, Pietro; Cancrini, Caterina; Mazzina, Oscar; Fiocchi, Alessandro

2015-12-01

The effects of an immunoadsorption procedure, specifically designed to remove immunoglobulin E (IgE), on food-induced anaphylaxis have never been evaluated. We evaluate the effects of IgE removal on the allergic thresholds to foods. A 6-year-old boy with anaphylaxis to multiple foods and steroid-resistant unstable allergic asthma displayed serum IgE levels of 2800 to 3500 kU/L. To lower IgE serum concentrations, which could be overridden by a high dose of omalizumab, 1.5 plasma volumes were exchanged in 8 apheresis sessions. During the procedure, serum IgE levels fell to 309 kU/L. After the procedure, the threshold of reactivity to baked milk increased from 0.125 to 5 g of milk protein (full tolerance) after the first session, and the threshold of reactivity to hazelnut increased from 0.037 to 0.142 g of protein after the first session, 0.377 g after the eighth, and 1.067 g (full tolerance) after the first administration of omalizumab. Immediately after the sixth IgE immunoadsorption, we started omalizumab therapy. In the next 40 days, the threshold of reactivity to hazelnut increased to 7.730 (full tolerance). Asthma control was obtained, treatment with montelukast was stopped, and fluticasone was tapered from 500 to 175 μg/day. The boy became partially or fully tolerant to all the tested foods, and quality of life was improved. IgE immunoadsorption, used to establish the starting basis for omalizumab administration, is able to increase the tolerance threshold to foods. Copyright © 2015 by the American Academy of Pediatrics.

Early life IgE responses in children living in the tropics: a prospective analysis.

PubMed

Zakzuk, Josefina; Acevedo, Nathalie; Cifuentes, Liliana; Bornacelly, Adriana; Sánchez, Jorge; Ahumada, Velky; Ring, Johannes; Ollert, Markus; Caraballo, Luis

2013-12-01

There are few birth cohort studies analyzing IgE sensitization in the tropics. We aimed to describe the evolution of total IgE and specific IgE responses to house-dust mite (HDM) allergens and Ascaris in a birth cohort (Risk Factors for Asthma and Allergy in the Tropics, FRAAT), analyzing their relationships with wheezing. Total and specific IgE were measured by ImmunoCap in mothers and children at four different time points (S1-S4) between 0 and 42 months. Parasite infection was evaluated by stool examination. Maternal total IgE (aOR: 2.43, 95% CI: 1.09-5.43; p = 0.03) and socio-demographic factors were associated with high cord blood (CB) total IgE. High CB total IgE was positively associated with higher Blomia tropicalis and Ascaris-specific IgE values during lifetime, but protected from recurrent wheezing (aOR: 0.26, 95% CI: 0.08-0.88, p = 0.03). Prevalence rates of IgE sensitization were high; at around 3 yr old, they were 33.3, 18.6, and 26.5% for B. tropicalis, Dermatophagoides pteronyssinus, and Ascaris, respectively. Indicators of unhygienic conditions were risk factors for HDM and Ascaris sensitization in children. A weak statistical association between B. tropicalis-specific IgE and ever wheezing was found (aOR: 1.47 95% CI: 1.00-2.28, p = 0.05). In a socioeconomically deprived community from the tropics, sensitization to HDM allergens was very frequent at early life, especially to B. tropicalis. In contrast to expected according to the hygiene hypothesis, unhygienic/poverty conditions were risk factors for allergen sensitization. High CB total IgE levels were a risk factor for allergen sensitization but protected from recurrent wheezing. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

IgE antibody to fish gelatin (type I collagen) in patients with fish allergy.

PubMed

Sakaguchi, M; Toda, M; Ebihara, T; Irie, S; Hori, H; Imai, A; Yanagida, M; Miyazawa, H; Ohsuna, H; Ikezawa, Z; Inouye, S

2000-09-01

Most children with anaphylaxis to measles, mumps, and rubella vaccines had shown sensitivity to bovine gelatin that was included in the vaccines. Recently, it was found that bovine type I collagen, which is the main content in the gelatin, is a major allergen in bovine gelatin allergy. Fish meat and skin also contain type I collagen. The present study was designed to investigate IgE antibody to fish gelatin in children with fish allergy. Serum samples were taken from patients in 3 groups: (1) 10 patients with fish allergy and specific IgE to fish meat; (2) two patients with allergies to both fish meat and bovine gelatin and specific IgE to fish meat and bovine gelatin; and (3) 15 patients with atopic dermatitis and specific IgE to fish meat. Various fish gelatins (type I collagen) were prepared from fish skin. IgE antibody to fish gelatin was analyzed by using ELISA and immunoblotting. Of 10 patients with fish allergy, 3 had specific IgE to fish gelatin. Of two patients with fish allergy and bovine gelatin allergy, all had specific IgE to fish gelatin. Of 15 patients with atopic dermatitis and specific IgE to fish meat, 5 had specific IgE to fish gelatin. Furthermore, IgE from pooled serum of the patients reacted with both the alpha1 and alpha2 chains of fish type I collagen in immunoblots. There is cross-reactivity among gelatins from various fishes, but there is little cross-reactivity between fish and bovine gelatins. Some fish-sensitive patients possessed IgE antibody to fish gelatin. Fish gelatin (type I collagen) might be an allergen in subjects with fish allergy.

Kissing selectively decreases allergen-specific IgE production in atopic patients.

PubMed

Kimata, H

2006-05-01

Stress enhanced allergic skin wheal responses and allergen-specific IgE production. In contrast, mothers' kissing caused relaxation in infants, and kissing by lovers or spouses to atopic patients reduced allergic skin wheal responses. I studied the effect of kissing on production of allergen-specific IgE and cytokines in atopic patients. Twenty-four patients with mild atopic eczema and 24 patients with mild allergic rhinitis kissed with lovers or spouses freely for 30 min while listening to soft music. Just before and immediately after kissing, blood mononuclear cells were separated cultured for allergen, and production of allergen-specific immunoglobulin and cytokine was measured. Kissing selectively decreased allergen-specific IgE production with skewing cytokine pattern toward Th1 type. Kissing may alleviate allergic symptoms by decrease in allergen-specific IgE production.

Allergen-induced cytokine production, atopic disease, IgE, and wheeze in children.

PubMed

Contreras, J Paola; Ly, Ngoc P; Gold, Diane R; He, Hongzhen; Wand, Mathew; Weiss, Scott T; Perkins, David L; Platts-Mills, Thomas A E; Finn, Patricia W

2003-12-01

The early childhood allergen-induced immune responses associated with atopic disease and IgE production in early life are not well understood. We assessed the relationship of allergen-induced cytokine production by PBMCs to both atopic disease and to IgE increase in a cohort of children with a parental history of allergy or asthma (n = 112) at a median of 2 years of age. We examined cockroach (Bla g 1)-induced, house dust mite (Der f 1)-induced, and cat (Fel d 1)-induced cytokine secretion, including secretion of IFN-gamma, IL-13, IL-10, and TNF-alpha. We investigated whether distinct cytokine patterns associated with atopic disease can be detected in immune responses of children. PBMCs were isolated, and allergen-induced cytokine secretion was analyzed by means of ELISA. Atopic disease was defined as physician- or nurse-diagnosed eczema or hay fever. Increased IgE was defined as an IgE level of greater than 35 U/mL to dust mite, cockroach, cat, and egg white or a total IgE level of 60 U/mL or greater. Compared with children without atopic disease, children with atopic disease had lower Der f 1 (P =.005) and Bla g 2 (P =.03) allergen-induced IFN-gamma levels. Compared with children without increased IgE (n = 95), those with increased IgE (n = 16) had higher Der f 1-induced (P =.006) and Fel d 1-induced (P =.005) IL-13 levels and lower Bla g 2-induced (P =.03) IFN-gamma levels. Compared with children with neither atopic disease nor repeated wheeze, children with both atopic disease and repeated wheeze had lower levels of allergen-induced IFN-gamma (P =.01 for Der f 1 and P =.02 for Bla g 2) cytokine secretion. In young children at risk for asthma or allergy, decreased allergen-induced IFN-gamma secretion is associated with atopic disease and, in some cases, with increased IgE levels. Increased allergen-induced IL-13 secretion is most strongly associated with early life increase of IgE.

An automated multiplex specific IgE assay system using a photoimmobilized microarray.

PubMed

Ito, Yoshihiro; Moritsugu, Nozomi; Matsue, Takahisa; Mitsukoshi, Kiyomi; Ayame, Hirohito; Okochi, Norihiko; Hattori, Hideshi; Tashiro, Hideo; Sato, Sakura; Ebisawa, Motohiro

2012-11-15

An automated microarray diagnostic system for specific IgE using photoimmobilized allergen has been developed. Photoimmobilization is useful for preparing microarrays, where various types of biological components are covalently immobilized on a plate. Because the immobilization is based on a photo-induced radical cross-linking reaction, it does not require specific functional groups on the immobilized components. Here, an aqueous solution of a photoreactive poly(ethylene glycol)-based polymer was spin-coated on a plate, and an aqueous solution of each allergen was microspotted on the coated plate and allowed to dry in air. Finally, the plate was irradiated with an ultraviolet lamp for covalent immobilization. An automated machine using these plates was developed for the assay of antigen-specific IgE. Initially, the patient serum was added to the microarray plate, and after reaction of the microspotted allergen with IgE, the adsorbed IgE was detected by a peroxidase-conjugated anti-IgE-antibody. The chemical luminescence intensity of the substrate decomposed by the peroxidase was automatically detected using a sensitive charge-coupled device camera. All the allergens were immobilized stably using this method, which was used to screen for allergen-specific IgE. The results were comparable with those using conventional specific IgE. Using this system, six different allergen-specific IgE were assayed using 10 μL of serum within a period of 20 min. Copyright © 2012 Elsevier B.V. All rights reserved.

The 28-entity IGES test file results using ComputerVision CADDS 4X

NASA Technical Reports Server (NTRS)

Kuan, Anchyi; Shah, Saurin; Smith, Kevin

1987-01-01

The investigation was based on the following steps: (1) Read the 28 Entity IGES (Initial Graphics Exchange Specification) Test File into the CAD data base with the IGES post-processor; (2) Make the modifications to the displayed geometries, which should produce the normalized front view and the drawing entity defined display; (3) Produce the drawing entity defined display of the file as it appears in the CAD system after modification to the geometry; (4) Translate the file back to IGES format using IGES pre-processor; (5) Read the IGES file produced by the pre-processor back into the CAD data base; (6) Produce another drawing entity defined display of the CAD display; and (7) Compare the plots resulting from steps 3 and 6 - they should be identical to each other.

Aeroallergen and food IgE sensitization and local and systemic inflammation in asthma.

PubMed

Patelis, A; Janson, C; Borres, M P; Nordvall, L; Alving, K; Malinovschi, A

2014-03-01

We recently reported an independent association between IgE sensitization to food allergens and increased airway inflammation, assessed by fraction of exhaled nitric oxide (FeNO), in a population-based study (J Allergy Clin Immunol, 130, 2012, 397). Similar studies have not been performed in populations with asthma. The aim of the present study was to investigate the allergic sensitization profile in asthmatics and examine FeNO, airway responsiveness and blood eosinophilia in relation to type and degree of IgE sensitization. FeNO, airway responsiveness, blood eosinophil count (B-Eos) and IgE sensitization to food allergens and aeroallergens were determined in 408 subjects with asthma, aged 10-34 years. Asthmatics had higher prevalence of IgE sensitization against all allergens than controls (P < 0.001). Mite, pollen, furry animal, mould and food sensitizations were each associated with increased FeNO, airway responsiveness and B-Eos in asthmatics. IgE sensitization to mould, furry animals and food allergens was independently related to FeNO (all P < 0.05) after adjustment for age, sex, height, smoking history and medication. IgE sensitization to mould (P < 0.001) and furry animals (P = 0.02) was related to airway responsiveness in a similar model. Finally, IgE sensitization to mould (P = 0.001), furry animals (P < 0.001) and food allergens (P < 0.001) was independently related to B-Eos. Independent effects of IgE sensitization to aeroallergens (furry animals and mould) and food allergens were found on both local and systemic markers of inflammation in asthma. The finding regarding food IgE sensitization is novel, and a clinical implication might be that even food sensitization must be assessed to fully understand inflammation patterns in asthma. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Multiple independent IgE epitopes on the highly allergenic grass pollen allergen Phl p 5.

PubMed

Levin, M; Rotthus, S; Wendel, S; Najafi, N; Källström, E; Focke-Tejkl, M; Valenta, R; Flicker, S; Ohlin, M

2014-11-01

Group 5 allergens are small proteins that consist of two domains. They belong to the most potent respiratory allergens. To determine the binding sites and to study allergic patients' IgE recognition of the group 5 allergen (Phl p 5) from timothy grass pollen using human monoclonal IgE antibodies that have been isolated from grass pollen allergic patients. Using recombinant isoallergens, fragments, mutants and synthetic peptides of Phl p 5, as well as peptide-specific antibodies, the interaction of recombinant human monoclonal IgE and Phl p 5 was studied using direct binding and blocking assays. Cross-reactivity of monoclonal IgE with group 5 allergens in several grasses was studied and inhibition experiments with patients' polyclonal IgE were performed. Monoclonal human IgE showed extensive cross-reactivity with group 5 allergens in several grasses. Despite its small size of 29 kDa, four independent epitope clusters on isoallergen Phl p 5.0101, two in each domain, were recognized by human IgE. Isoallergen Phl p 5.0201 carried two of these epitopes. Inhibition studies with allergic patients' polyclonal IgE suggest the presence of additional IgE epitopes on Phl p 5. Our results reveal the presence of a large number of independent IgE epitopes on the Phl p 5 allergen explaining the high allergenic activity of this protein and its ability to induce severe allergic symptoms. High-density IgE recognition may be a general feature of many potent allergens and form a basis for the development of improved diagnostic and therapeutic procedures in allergic disease. © 2014 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

Multiple independent IgE epitopes on the highly allergenic grass pollen allergen Phl p 5

PubMed Central

Levin, M; Rotthus, S; Wendel, S; Najafi, N; Källström, E; Focke-Tejkl, M; Valenta, R; Flicker, S; Ohlin, M

2014-01-01

Background Group 5 allergens are small proteins that consist of two domains. They belong to the most potent respiratory allergens. Objective To determine the binding sites and to study allergic patients' IgE recognition of the group 5 allergen (Phl p 5) from timothy grass pollen using human monoclonal IgE antibodies that have been isolated from grass pollen allergic patients. Methods Using recombinant isoallergens, fragments, mutants and synthetic peptides of Phl p 5, as well as peptide-specific antibodies, the interaction of recombinant human monoclonal IgE and Phl p 5 was studied using direct binding and blocking assays. Cross-reactivity of monoclonal IgE with group 5 allergens in several grasses was studied and inhibition experiments with patients' polyclonal IgE were performed. Results Monoclonal human IgE showed extensive cross-reactivity with group 5 allergens in several grasses. Despite its small size of 29 kDa, four independent epitope clusters on isoallergen Phl p 5.0101, two in each domain, were recognized by human IgE. Isoallergen Phl p 5.0201 carried two of these epitopes. Inhibition studies with allergic patients' polyclonal IgE suggest the presence of additional IgE epitopes on Phl p 5. Conclusions & Clinical Relevance Our results reveal the presence of a large number of independent IgE epitopes on the Phl p 5 allergen explaining the high allergenic activity of this protein and its ability to induce severe allergic symptoms. High-density IgE recognition may be a general feature of many potent allergens and form a basis for the development of improved diagnostic and therapeutic procedures in allergic disease. PMID:25262820

Effect of urbanisation on the relationship between total serum IgE and asthma.

PubMed

Checkley, William; Robinson, Colin L; Baumann, Lauren M; Romero, Karina; Combe, Juan M; Gilman, Robert H; Wise, Robert A; Hamilton, Robert G; Gonzalvez, Guillermo; Cama, Vitaliano; Hansel, Nadia N

2013-05-01

It is unclear if the relationship of total serum IgE with asthma varies with degree of urbanisation. We hypothesised that the relationship of total serum IgE to asthma is more pronounced in an urban versus a rural environment. We enrolled 1441 children aged 13-15 years in a peri-urban shanty town in Lima, Peru (n=725) and 23 villages in rural Tumbes, Peru (n=716). We asked participants about asthma and allergy symptoms, environmental exposures and sociodemographics; and performed spirometry, and exhaled nitric oxide and allergy skin testing. We obtained blood for total serum IgE in 1143 (79%) participants. Geometric means for total serum IgE were higher in Lima versus Tumbes (262 versus 192 kU·L(-1); p<0.001). The odds of asthma increased by factors of 1.6 (95% CI 1.3-2.0) versus 1.4 (95% CI 0.9-2.1) per log unit increase in total serum IgE in Lima versus Tumbes, respectively. Atopy was an effect modifier of the relationship of total serum IgE on asthma. Among atopics and non-atopics, the odds of asthma increased by a factor of 2.0 (95% CI 1.5-2.7) and 1.0 (95% CI 0.7-1.4) per log unit increase in total serum IgE, respectively. Total serum IgE was associated with atopic asthma but not with non-atopic asthma. Urbanisation did not appear to be an effect modifier of this relationship.

Autoimmune response of IgE antibodies to cellular self-antigens in systemic Lupus Erythematosus.

PubMed

Atta, Ajax Mercês; Santiago, Mittermayer Barreto; Guerra, Fernanda Garcia; Pereira, Mariana Menezes; Sousa Atta, Maria Luiza B

2010-01-01

Systemic lupus erythematosus (SLE) patients may exhibit high total IgE and antinuclear IgE antibodies (ANA-IgE). Here, we investigated the specificity of ANA-IgE in SLE patients and the involvement of cytokines in this immune response. Sera from 92 SLE patients and 68 healthy controls were evaluated for the presence of antinuclear IgE antibodies by immunoperoxidase with HEp-2,000(R) cells and immunoblotting with IgG-depleted sera. Total IgE, IgE specific to allergens, and serum cytokine levels were determined by ELISA. Antinuclear IgE antibodies were detected only in SLE patients (29/92, 31.5%). High total IgE was associated with ANA-IgE (p < 0.0001), but was not associated with IgE antibodies to allergens. In the immunoblotting, ANA-IgE reacted with nucleosomes (23/29, 79.3%), dsDNA (14/29, 48.3%), SS-A/Ro (14/29, 48.3%), SS-B/La (2/29, 18.7%), Sm (14/29, 48.3%) and RNP (18/29, 62.1%). Patients with ANA-IgE had very low serum IL-4, less IL-5 than controls (p < 0.05), more IL-10 than seronegative patients (p < 0.05), and unaltered IFN-gamma levels. The IL-5/IL-10 ratio was lower in ANA-IgE seropositive patients in comparison with either seronegative patients (p < 0.05) or healthy controls (p = 0.001). Controls displayed higher IL-5/IFN-gamma ratios than either SLE patients with ANA-IgE (p < 0.05) or patients without these immunoglobulins (p < 0.01). We conclude that IgE antibodies against cell autoantigens involved in protein expression, cellular proliferation, and cell death are present in patients with SLE. Interleukin-10 seems to down-regulate this IgE autoimmune response in SLE. Copyright 2010 S. Karger AG, Basel.

A chimeric IgE that mimics IgE from patients allergic to acid-hydrolyzed wheat proteins is a novel tool for in vitro allergenicity assessment of functionalized glutens

PubMed Central

Gaudin, Jean-Charles; Patil, Sarita; Steinbrecher, Johanna; Matsunaga, Kayoko; Teshima, Reiko; Sakai, Shinobu; Larré, Colette; Denery-Papini, Sandra

2017-01-01

Background Acid-hydrolyzed wheat proteins (acid-HWPs) have been shown to provoke severe allergic reactions in Europe and Japan that are distinct from classical wheat allergies. Acid-HWPs were shown to contain neo-epitopes induced by the deamidation of gluten proteins. However, products with variable rates of deamidation can be found. Objectives In this work, we studied the effect of the extent of wheat proteins deamidation on its allergenicity. A recombinant chimeric IgE was produced and compared to patients’ IgE for its capacity to assess the IgE-mediated triggering potential of acid-HWPs. Methods Sera from acid-HWP allergic patients were analyzed via ELISA and a functional basophil assay for their IgE reactivity to wheat proteins with different deamidation levels. A chimeric mouse/human IgE (chIgE-DG1) specific for the main neo-epitope, QPEEPFPE, involved in allergy to acid-HWPs was characterized with respect to its functionality and its reactivity compared to that of patients’ IgE. Results Acid-HWPs with medium (30%) and high (50–60%) deamidation levels displayed a markedly stronger IgE binding and capacity to activate basophils than those of samples with weak (15%) deamidation levels. The monoclonal chIgE-DG1 allowed basophil degranulation in the presence of deamidated wheat proteins. ChIgE-DG1 was found to mimic patients’ IgE reactivity and displayed the same ability to rank acid-HWP products in a degranulation assay. Conclusion Increasing the deamidation level of products from 15% to 60% resulted in an approximately 2-fold increase in their antigenicity and a 100-fold increase in their eliciting potential. The chimeric ChIgE-DG1 may be a useful tool to evaluate functionalized glutens for their allergenic potential. By mimicking patient sera reactivity, chIgE-DG1 also provided data on the patients' IgE repertoire and on the functionality of certain repeated epitopes in gluten proteins. PMID:29117222

A chimeric IgE that mimics IgE from patients allergic to acid-hydrolyzed wheat proteins is a novel tool for in vitro allergenicity assessment of functionalized glutens.

PubMed

Tranquet, Olivier; Gaudin, Jean-Charles; Patil, Sarita; Steinbrecher, Johanna; Matsunaga, Kayoko; Teshima, Reiko; Sakai, Shinobu; Larré, Colette; Denery-Papini, Sandra

2017-01-01

Acid-hydrolyzed wheat proteins (acid-HWPs) have been shown to provoke severe allergic reactions in Europe and Japan that are distinct from classical wheat allergies. Acid-HWPs were shown to contain neo-epitopes induced by the deamidation of gluten proteins. However, products with variable rates of deamidation can be found. In this work, we studied the effect of the extent of wheat proteins deamidation on its allergenicity. A recombinant chimeric IgE was produced and compared to patients' IgE for its capacity to assess the IgE-mediated triggering potential of acid-HWPs. Sera from acid-HWP allergic patients were analyzed via ELISA and a functional basophil assay for their IgE reactivity to wheat proteins with different deamidation levels. A chimeric mouse/human IgE (chIgE-DG1) specific for the main neo-epitope, QPEEPFPE, involved in allergy to acid-HWPs was characterized with respect to its functionality and its reactivity compared to that of patients' IgE. Acid-HWPs with medium (30%) and high (50-60%) deamidation levels displayed a markedly stronger IgE binding and capacity to activate basophils than those of samples with weak (15%) deamidation levels. The monoclonal chIgE-DG1 allowed basophil degranulation in the presence of deamidated wheat proteins. ChIgE-DG1 was found to mimic patients' IgE reactivity and displayed the same ability to rank acid-HWP products in a degranulation assay. Increasing the deamidation level of products from 15% to 60% resulted in an approximately 2-fold increase in their antigenicity and a 100-fold increase in their eliciting potential. The chimeric ChIgE-DG1 may be a useful tool to evaluate functionalized glutens for their allergenic potential. By mimicking patient sera reactivity, chIgE-DG1 also provided data on the patients' IgE repertoire and on the functionality of certain repeated epitopes in gluten proteins.

Epigenome-wide DNA methylation study of IgE concentration in relation to self-reported allergies.

PubMed

Ek, Weronica E; Ahsan, Muhammad; Rask-Andersen, Mathias; Liang, Liming; Moffatt, Miriam F; Gyllensten, Ulf; Johansson, Åsa

2017-04-01

Epigenetic mechanisms are critical for normal immune development and epigenetic alterations might therefore be possible contributors to immune diseases. To investigate if DNA methylation in whole blood is associated with total and allergen-specific IgE levels. We performed an epigenome-wide association study to investigate the association between DNA methylation and IgE level, allergen-specific IgE and self-reported immune diseases and allergies in 728 individuals. We identified and replicated 15 CpG sites associated with IgE, mapping to biologically relevant genes, including ACOT7, ILR5A, KCNH2, PRG2 and EPX. A total of 331 loci were associated with allergen-specific IgE, but none of these CpG sites were associated with self-reported allergies and immune diseases. This study shows that IgE levels are associated with DNA methylation levels at numerous CpG sites, which might provide new leads for investigating the links between IgE and allergic inflammation.

Glove-derived foreign proteins induce allergen-specific IgE in a mouse model.

PubMed

Busch, Marion; Schröder, Claudia; Baron, Jens-Malte; Ott, Hagen; Bruckner, Thomas; Diepgen, Thomas L; Mahler, Vera

2008-04-01

Currently, most medical gloves are produced with a low content of natural rubber latex (NRL) protein. However, they may be substituted by proteins of foreign origin to maintain specific properties of the material. The aim of this study was to investigate the allergenicity and immunogenicity of unexpected proteins (i.e., soy and casein) compared with NRL proteins in a murine model in BALB/c mice. All respective allergen sources (extracts from three brands of NRL gloves, soy, and casein) were able to induce significant allergen-specific IgE and IgG(1) responses. On average, the highest IgE induction occurred after immunization with NRL, followed by soy and casein. Certain individuals from each treatment group exhibited levels of specific IgE as high as due to NRL. To analyze further specific IgE responses on a single allergen level, we established a microarray based on recombinant allergens for allergen-specific murine IgE detection. Besides specific IgE against rHev b 3, -6, -7, -8, and -11, specific IgE against kappa-casein could be detected in mice immunized with NRL glove extract, indicating a sensitization potential of the contained foreign protein. The substitution of genuine latex proteins by proteins of foreign origin may lead to a shift and de novo increase in sensitization to the finished products.

The who, where, and when of IgE in allergic airway disease.

PubMed

Dullaers, Melissa; De Bruyne, Ruth; Ramadani, Faruk; Gould, Hannah J; Gevaert, Philippe; Lambrecht, Bart N

2012-03-01

Allergic asthma and allergic rhinitis/conjunctivitis are characterized by a T(H)2-dominated immune response associated with increased serum IgE levels in response to inhaled allergens. Because IgE is a key player in the induction and maintenance of allergic inflammation, it represents a prime target for therapeutic intervention. However, our understanding of IgE biology remains fragmentary. This article puts together our current knowledge on IgE in allergic airway diseases with a special focus on the identity of IgE-secreting cells ("who"), their location ("where"), and the circumstances in which they are induced ("when"). We further consider the therapeutic implications of the insights gained. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

NASA geometry data exchange specification for computational fluid dynamics (NASA IGES)

NASA Technical Reports Server (NTRS)

Blake, Matthew W.; Kerr, Patricia A.; Thorp, Scott A.; Jou, Jin J.

1994-01-01

This document specifies a subset of an existing product data exchange specification that is widely used in industry and government. The existing document is called the Initial Graphics Exchange Specification. This document, a subset of IGES, is intended for engineers analyzing product performance using tools such as computational fluid dynamics (CFD) software. This document specifies how to define mathematically and exchange the geometric model of an object. The geometry is represented utilizing nonuniform rational B-splines (NURBS) curves and surfaces. Only surface models are represented; no solid model representation is included. This specification does not include most of the other types of product information available in IGES (e.g., no material properties or surface finish properties) and does not provide all the specific file format details of IGES. The data exchange protocol specified in this document is fully conforming to the American National Standard (ANSI) IGES 5.2.

Immunoglobulin E (IgE) and IgE-containing cells in human gastrointestinal fluids and tissues.

PubMed Central

Brown, W R; Borthistle, B K; Chen, S T

1975-01-01

Human gastric, small intestinal, colonic and rectal mucosae were examined for IgE-containing cells by single- and double-antibody immunofluorescence techniques, and IgE in intesinal fluids was measured by a double-antibody radioimmunoassay. IgE-containing cells were identified in all tissue specimens and comprised about 2% of all immunoglobulin-containing cells. Although less numerous than cells containing IgA, IgM or IgG, they were remarkably numerous in relation to the concentration of IgE in serum (about 0-001% of total immunoglobulin). IgE immunocytes were significantly more numerous in stomach and proximal small bowel than in colon and rectum, and were very numerous at bases of gastric and duodenal peptic ulcers. Measurable IgE was found in seventy-eight of eighty-five (92%) intestinal fluids. Sucrose gradient ultracentrifugation analysis of four of the fluids revealed that the immunologically reactive IgE was largely in fractions corresponding to molecules of lower molecular weight than that of albumin, which suggests that IgE in gut contents is degraded by proteolytic enzymes. The presence of IgE-forming cells in gastrointestinal tissues, and IgE or a fragment of IgE in intestinal fluids, suggests that IgE antibodies are available for participation in local reaginic-type reactions in the gut. Images FIG. 1 PMID:813925

IgE and IgG antibodies in skin allergy of the horse.

PubMed

Wagner, Bettina; Miller, William H; Morgan, Erin E; Hillegas, Julia M; Erb, Hollis N; Leibold, Wolfgang; Antczak, Douglas F

2006-01-01

In horses, allergies have been characterized by clinical signs and/or intradermal (i.d.) allergen testing. Our aim was to find the first direct evidence that immunoglobulin E (IgE) mediates equine allergy. In addition, we tested the hypothesis that immediate skin reactions in horses can also be mediated by IgG. Anti-IgE affinity columns were used to purify IgE from serum of one healthy horse and three horses affected with summer eczema, an allergic dermatitis which is believed to be induced by Culicoides midges. A modified Prausnitz-Küstner experiment was performed in four clinical healthy horses by i.d. injection of the purified serum IgE antibodies. The following day, Culicoides allergen was injected at the same sites. Skin reactions were not observed in response to allergen alone, and in two horses after stimulation at any previous IgE injection site. However, the other two horses showed an immediate skin reaction at the previous injection sites of IgE obtained from allergic horses. In addition, purified monoclonal antibodies to various equine immunoglobulin isotypes were injected i.d. into six healthy horses. Immediate skin reactions were observed in response to anti-IgE (6/6 horses) and anti-IgG(T) injections (5/6 horses). The specificities of both antibodies for IgE and IgG(T), respectively, were confirmed by enzyme linked immunosorbent assays. The results provide the first direct evidence that IgE mediates classical Type-I allergy in horses and plays a major role in the pathogenesis of summer eczema. The data also suggest that IgG(T) can bind to skin mast cells and might contribute to clinical allergy.

Total and Toxocara canis larval excretory/secretory antigen- and allergen-specific IgE in atopic and non-atopic dogs.

PubMed

Zwickl, Lena L M N; Joekel, Deborah E; Fischer, Nina M; Rostaher, Ana; Thamsborg, Kristian; Deplazes, Peter; Favrot, Claude

2018-06-01

Total IgE concentrations are higher in dogs than in humans. Persistent Toxocara canis larval infection is prevalent in dogs and is associated with substantial specific antibody reactions. A correlation, however, between total IgE and T. canis-specific antibody levels in dogs has not been evaluated. To determine the relationship between total IgE, T. canis-specific IgG and IgE, and allergen-specific IgE levels in atopic and non-atopic dogs, and to evaluate possible confounding factors. Sera of 30 atopic and 30 non-atopic client-owned dogs. Total IgE, T. canis-specific antibody and allergen-specific IgE levels were evaluated by ELISA. Total IgE, T. canis-specific antibody and allergen-specific IgE levels were significantly higher in non-atopic compared to atopic dogs. A positive correlation was demonstrated between T. canis-specific IgG and T. canis-specific IgE; T. canis-specific IgG and total IgE; T. canis-specific IgE and total IgE; and allergen-specific IgE and total IgE. No differences were detected on the basis of age, gender, vaccination status; deworming or season between atopic and non-atopic dogs. Previous immunomodulatory treatment and cause of atopy did not influence antibody levels of atopic dogs. Toxocara canis-specific IgE appears to be a major component of total IgE in dogs. Total and T. canis-specific IgE levels are higher in non-atopic compared to atopic dogs. It is speculated that T. canis infection may have a protective effect against the development of canine atopic dermatitis and/or that elevations in total serum IgE level are often not associated with atopic dermatitis. © 2018 ESVD and ACVD.

Determinants of venom-specific IgE antibody concentration during long-term wasp venom immunotherapy.

PubMed

Pravettoni, Valerio; Piantanida, Marta; Primavesi, Laura; Forti, Stella; Pastorello, Elide A

2015-01-01

Venom immunotherapy (VIT) is an effective treatment for subjects with systemic allergic reactions (SR) to Hymenoptera stings, however there are few studies concerning the relevance of the venom specific IgE changes to decide about VIT cessation. We assessed IgE changes during a 5-year VIT, in patients stung and protected within the first 3 years (SP 0-3) or in the last 2 years (SP 3-5), and in patients not stung (NoS), to evaluate possible correlations between IgE changes and clinical protection. Yellow jacket venom (YJV)-allergic patients who completed 5 years of VIT were retrospectively evaluated. Baseline IgE levels and after the 3rd and the 5th year of VIT were determined; all patients were asked about field stings and SRs. A total of 232 YJV-allergic patients were included and divided into the following groups: 84 NoS, 72 SP 0-3 and 76 SP 3-5. IgE levels decreased during VIT compared to baseline values (χ(2) = 346.029, p < 0.001). Recent vespid stings accounted for significantly higher IgE levels despite clinical protection. IgE levels after 5 years of VIT correlated significantly with Mueller grade (F = 2.778, p = 0.012) and age (F = 6.672, p = 0.002). During follow-up from 1 to 10 years after VIT discontinuation, 35.2 % of the contacted patients reported at least one field sting without SR. The yellow jacket-VIT temporal stopping criterion of 5 years duration did not result in undetectable IgE levels, despite a long-lasting protection. A mean IgE decrease from 58 to 70 % was observed, and it was less marked in elderly patients or in subjects with higher Mueller grade SR.

IgE and mast cells in host defense against parasites and venoms

PubMed Central

Mukai, Kaori; Tsai, Mindy; Galli, Stephen J.

2016-01-01

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. PMID:27225312

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

PubMed

Mukai, Kaori; Tsai, Mindy; Starkl, Philipp; Marichal, Thomas; Galli, Stephen J

2016-09-01

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.

Effect of urbanisation on the relationship between total serum IgE and asthma

PubMed Central

Checkley, William; Robinson, Colin L.; Baumann, Lauren M.; Romero, Karina; Combe, Juan M.; Gilman, Robert H.; Wise, Robert A.; Hamilton, Robert G.; Gonzalvez, Guillermo; Cama, Vitaliano; Hansel, Nadia N.

2017-01-01

It is unclear if the relationship of total serum IgE with asthma varies with degree of urbanisation. We hypothesised that the relationship of total serum IgE to asthma is more pronounced in an urban versus a rural environment. We enrolled 1441 children aged 13–15 years in a peri-urban shanty town in Lima, Peru (n=725) and 23 villages in rural Tumbes, Peru (n=716). We asked participants about asthma and allergy symptoms, environmental exposures and sociodemographics; and performed spirometry, and exhaled nitric oxide and allergy skin testing. We obtained blood for total serum IgE in 1143 (79%) participants. Geometric means for total serum IgE were higher in Lima versus Tumbes (262 versus 192 kU·L−1; p<0.001). The odds of asthma increased by factors of 1.6 (95% CI 1.3–2.0) versus 1.4 (95% CI 0.9–2.1) per log unit increase in total serum in Lima versus Tumbes, respectively. Atopy was an effect modifier of the relationship of total serum IgE on asthma. Among atopics and non-atopics, the odds of asthma increased by a factor of 2.0 (95% CI 1.5–2.7) and 1.0 (95% CI 0.7–1.4) per log unit increase in total serum IgE, respectively. Total serum IgE was associated with atopic asthma but not with non-atopic asthma. Urbanisation did not appear to be an effect modifier of this relationship. PMID:22835619

Two Loci on Chromosome 5 Are Associated with Serum IgE Levels in Labrador Retrievers

PubMed Central

Owczarek-Lipska, Marta; Lauber, Béatrice; Molitor, Vivianne; Meury, Sabrina; Kierczak, Marcin; Tengvall, Katarina; Webster, Matthew T.; Jagannathan, Vidhya; Schlotter, Yvette; Willemse, Ton; Hendricks, Anke; Bergvall, Kerstin; Hedhammar, Åke; Andersson, Göran; Lindblad-Toh, Kerstin; Favrot, Claude; Roosje, Petra; Marti, Eliane; Leeb, Tosso

2012-01-01

Crosslinking of immunoglobulin E antibodies (IgE) bound at the surface of mast cells and subsequent mediator release is considered the most important trigger for allergic reactions. Therefore, the genetic control of IgE levels is studied in the context of allergic diseases, such as asthma, atopic rhinitis, or atopic dermatitis (AD). We performed genome-wide association studies in 161 Labrador Retrievers with regard to total and allergen-specific immunoglobulin E (IgE) levels. We identified a genome-wide significant association on CFA 5 with the antigen-specific IgE responsiveness to Acarus siro. We detected a second genome-wide significant association with respect to the antigen-specific IgE responsiveness to Tyrophagus putrescentiae at a different locus on chromosome 5. A. siro and T. putrescentiae both belong to the family Acaridae and represent so-called storage or forage mites. These forage mites are discussed as major allergen sources in canine AD. No obvious candidate gene for the regulation of IgE levels is located under the two association signals. Therefore our studies offer a chance of identifying a novel mechanism controlling the host's IgE response. PMID:22720065

Computationally predicted IgE epitopes of walnut allergens contribute to cross-reactivity with peanuts

PubMed Central

Maleki, Soheila J.; Teuber, Suzanne S.; Cheng, Hsiaopo; Chen, Deliang; Comstock, Sarah S.; Ruan, Sanbao; Schein, Catherine H.

2011-01-01

Background Cross reactivity between peanuts and tree nuts implies that similar IgE epitopes are present in their proteins. Objective To determine whether walnut sequences similar to known peanut IgE binding sequences, according to the property distance (PD) scale implemented in the Structural Database of Allergenic Proteins (SDAP), react with IgE from sera of patients with allergy to walnut and/or peanut. Methods Patient sera were characterized by Western blotting for IgE-binding to nut protein extracts, and to peptides from walnut and peanut allergens, similar to known peanut epitopes as defined by low PD values, synthesized on membranes. Competitive ELISA was used to show that peanut and predicted walnut epitope sequences compete with purified Ara h 2 for binding to IgE in serum from a cross-reactive patient. Results Sequences from the vicilin walnut allergen Jug r 2 which had low PD values to epitopes of the peanut allergen Ara h 2, a 2s-albumin, bound IgE in sera from five patients who reacted to either walnut, peanut or both. A walnut epitope recognized by 6 patients mapped to a surface-exposed region on a model of the N-terminal pro-region of Jug r 2. A predicted walnut epitope competed for IgE binding to Ara h 2 in serum as well as the known IgE epitope from Ara h 2. Conclusions Sequences with low PD value (<8.5) to known IgE epitopes could contribute to cross-reactivity between allergens. This further validates the PD scoring method for predicting cross-reactive epitopes in allergens. PMID:21883278

Diagnostic Utility of Total IgE in Foods, Inhalant, and Multiple Allergies in Saudi Arabia.

PubMed

Al-Mughales, Jamil A

2016-01-01

Objective. To assess the diagnostic significance of total IgE in foods, inhalant, and multiple allergies. Methods. Retrospective review of the laboratory records of patients who presented with clinical suspicion of food or inhalant allergy between January 2013 and December 2014. Total IgE level was defined as positive for a value >195 kU/L; and diagnosis was confirmed by the detection of specific IgE (golden standard) for at least one food or inhalant allergen and at least two allergens in multiple allergies. Results. A total of 1893 (male ratio = 0.68, mean age = 39.0 ± 19.2 years) patients were included. Total IgE had comparable sensitivity (55.8% versus 59.6%) and specificity (83.9% versus 84.4%) in food versus inhalant allergy, respectively, but a superior PPV in inhalant allergy (79.1% versus 54.4%). ROC curve analysis showed a better diagnostic value in inhalant allergies (AUC = 0.817 (95% CI = 0.796-0.837) versus 0.770 (95% CI = 0.707-0.833)). In multiple allergies, total IgE had a relatively good sensitivity (78.6%), while negative IgE testing (<195 kU/L) predicted the absence of multiple allergies with 91.5% certitude. Conclusion. Total IgE assay is not efficient as a diagnostic test for foods, inhalant, or multiple allergies. The best strategy should refer to specific IgE testing guided by a comprehensive atopic history.

Diagnostic Utility of Total IgE in Foods, Inhalant, and Multiple Allergies in Saudi Arabia

PubMed Central

Al-Mughales, Jamil A.

2016-01-01

Objective. To assess the diagnostic significance of total IgE in foods, inhalant, and multiple allergies. Methods. Retrospective review of the laboratory records of patients who presented with clinical suspicion of food or inhalant allergy between January 2013 and December 2014. Total IgE level was defined as positive for a value >195 kU/L; and diagnosis was confirmed by the detection of specific IgE (golden standard) for at least one food or inhalant allergen and at least two allergens in multiple allergies. Results. A total of 1893 (male ratio = 0.68, mean age = 39.0 ± 19.2 years) patients were included. Total IgE had comparable sensitivity (55.8% versus 59.6%) and specificity (83.9% versus 84.4%) in food versus inhalant allergy, respectively, but a superior PPV in inhalant allergy (79.1% versus 54.4%). ROC curve analysis showed a better diagnostic value in inhalant allergies (AUC = 0.817 (95% CI = 0.796–0.837) versus 0.770 (95% CI = 0.707–0.833)). In multiple allergies, total IgE had a relatively good sensitivity (78.6%), while negative IgE testing (<195 kU/L) predicted the absence of multiple allergies with 91.5% certitude. Conclusion. Total IgE assay is not efficient as a diagnostic test for foods, inhalant, or multiple allergies. The best strategy should refer to specific IgE testing guided by a comprehensive atopic history. PMID:27314052

Ferulic acid enhances IgE binding to peanut allergens in western blots.

USDA-ARS?s Scientific Manuscript database

Because phenolic compounds can precipitate or complex with proteins, we postulated that interactions of phenolics with IgE antibodies help enhance IgE binding to peanut allergens in Western blots. Three different phenolics, such as, ferulic, caffeic and chlorogenic acids were examined. Each was mixe...

IgE low affinity receptor (CD23) expression, Plasmodium falciparum specific IgE and tumor necrosis factor-alpha production in Thai uncomplicated and severe falciparum malaria patients.

PubMed

Kumsiri, Ratchanok; Troye-Blomberg, Marita; Pattanapanyasat, Kovit; Krudsood, Srivicha; Maneerat, Yaowapa

2016-02-01

Previous studies have suggested that Plasmodium falciparum (P. falciparum) specific IgE in the form of immune complexes crosslinking the low-affinity receptor (CD23) on monocyte results in tumor necrosis factor (TNF)-α and nitric oxide (NO) production. However, the roles of these parameters in severity and immune protection are still unclear. This study aimed to determine the association between CD23 expression on monocytes, plasma soluble CD23 (sCD23), total IgE, malaria-specific IgE and IgG, and TNF-α levels in P. falciparum infected patients. We evaluated 64 uncomplicated (UC) and 25 severe patients (S), admitted at the Hospital for Tropical Diseases, Mahidol University, and 34 healthy controls (C) enrolled in 2001. Flow cytometry and enzyme linked immunosorbent assays (ELISA) demonstrated that trends of the CD23 expression, levels of sCD23 and specific IgE were higher in the S group as compared to those in the UC and C groups. Plasma levels of P. falciparum specific IgE in the UC (p=0.011) and S groups (p=0.025) were significantly higher than those in C group. In contrast the TNF-α levels tended to be higher in the UC than those in the S (p=0.343) and significantly higher than those in C (p=0.004) groups. The specific IgG levels in UC were significantly higher than those in S and C (p<0.001) groups. At admission, a strong significant negative correlation was found between specific IgG and sCD23 (r=-0.762, p=0.028), and TNF-α and IgE-IgG complexes (r=-0.715, p=0.002). Significant positive correlations between levels of specific IgE and TNF-α (r=0.575, p=0.010); and sCD23 (r=0.597, p=0.000) were also observed. In conclusion, our data suggest that CD23 expression and malaria-specific IgE levels may be involved in the severity of the disease while TNF-α and the malaria-specific IgG may correlate with protection against falciparum malaria. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Correlation of serum IgE levels and clinical manifestations in patients with actinic prurigo*

PubMed Central

Cuevas-Gonzalez, Juan Carlos; Lievanos-Estrada, Zahide; Vega-Memije, Maria Elisa; Hojyo-Tomoka, Maria Teresa; Dominguez-Soto, Luciano

2016-01-01

BACKGROUND: Actinic prurigo is an idiopathic photodermatosis, the pathophysiology of which has been hypothesized to involve subtype IV type b (Th2) hypersensitive response, whereby IL4, IL5, and IL13 are secreted and mediate the production of B cells, IgE, and IgG4. OBJECTIVES: To examine the association of serum IgE levels and the clinical severity of injuries. METHODS: This case-control study comprised patients with a clinical and histopathological diagnosis of actinic prurigo, as well as clinically healthy subjects, from whom 3cc of peripheral blood was taken for immunoassay. Cases were classified by lesion severity as mild, moderate, and severe. Descriptive statistics were analyzed, and chi-square test was performed. RESULTS: We included 21 actinic prurigo patients and 21 subjects without disease; 11 patients with actinic prurigo had elevated serum IgE levels, and 10 had low serum levels. Six actinic prurigo (AP) patients with elevated serum levels of IgE had moderate injuries, 4 had severe injuries, and 1 had minor injuries. Eight out of 10 patients with normal IgE levels presented with minor injuries in the clinical evaluation. The 21 controls did not have increased serum IgE levels. CONCLUSIONS: Elevated IgE levels are associated with moderate to severe clinical lesions, suggesting that actinic prurigo entails a type IV subtype b hypersensitivity response in which Th2 cells predominate. PMID:26982774

Reactivity change of IgE to buckwheat protein treated with high-pressure and enzymatic hydrolysis.

PubMed

Lee, Chaeyoon; In, Sooyeon; Han, Youngshin; Oh, Sangsuk

2016-04-01

Buckwheat is a popular food material in eastern Asian countries that can cause allergenic response. This study was conducted to evaluate the effects of hydrolysis with papain and high-pressure (HP) treatment of buckwheat protein (BWP) on reactivity of immunoglobulin E (IgE) and its secondary structure. Reactivity of IgE was examined by enzyme-linked immunosorbent assay (ELISA) with serum samples from 16 patients allergic to buckwheat. Reactivity of IgE to hydrolysate of BWP with papain showed a maximum decrease of 79.8%. After HP treatment at 600 MPa for 1 min, reactivity of IgE to BWP decreased by up to 55.1%. When extracted, BWP was hydrolyzed with papain overnight following HP treatment at 600 MPa which the reactivity of IgE decreased significantly by up to 87.1%. Significant changes in secondary structure of BWP were observed by circular dichroism (CD) analysis after hydrolysis with papain following HP treatment. Reduction of reactivity of IgE showed a correlation with changes in secondary structure of BWP, which may cause changes in conformational epitopes. This suggests the possibility of decreasing the reactivity of IgE to BWP using combined physical and enzymatic treatments. © 2015 Society of Chemical Industry.

[The expression and significance of IgE in anaphylactic shock guinea-pigs].

PubMed

Gong, Zhi-qiang; Xiao, Feng; Feng, Qiong; Xu, Xiao-ming; Zheng, Jian

2006-02-01

To seek the pathomorphological targets for forensic expertise in anaphylactic shock. The expression of IgE in hearts, lungs, livers, spleens, kidneys, gastrics, intestinals, tracheas and tonsils of anaphylactic shock guinea-pigs was observed at 0, 6, 12 h and 24 h respectively by tissue chip S-P immuno-histochemical method. Positive expression of IgE presented in lungs and tracheas in the test group with the peak at 0 hour and it declined as time advanced, and also there were significant differences at different times (P<0.05). The immuno-histochemical method of detecting the expression of IgE in lungs, tracheas and spleens can be supposed to be the pathomorphological targets for forensic expertise in anaphylactic shock. The weakening of the positive expression of IgE in lungs and tracheas as the time advanced suggested that in this kind of case the autopsy should be arried out as early as possible.

Immunosafety of recombinant human C1-inhibitor in hereditary angioedema: evaluation of ige antibodies.

PubMed

Hack, C Erik; Relan, Anurag; Baboeram, Aartie; Oortwijn, Beatrijs; Versteeg, Serge; van Ree, Ronald; Pijpstra, Rienk

2013-04-01

Recombinant human C1-inhibitor (rhC1INH) purified from milk of transgenic rabbits is used for the treatment of acute attacks in patients with hereditary angioedema (HAE) due to C1-inhibitor (C1INH) deficiency. The objective was to investigate the risk of rhC1INH inducing IgE antibodies or eliciting anaphylactic reactions. In subjects treated with rhC1INH, we retrospectively analysed the frequency and clinical relevance of pre-exposure and potentially newly induced IgE antibodies against rabbit and other animal allergens including cow's milk by the ImmunoCAP(®) Specific IgE blood test system. 130 HAE patients and 14 healthy subjects received 300 administrations of rhC1INH, 65 subjects (47.4 %) on one occasion; 72 (52.6 %) on at least two occasions (range 2-12; median 2). Five subjects had pre-existing anti-rabbit epithelium IgE; the subject with the highest levels and a previously undisclosed rabbit allergy developed an anaphylactic reaction upon first exposure to rhC1INH, whereas the other four subjects with lower pre-existing IgE levels (Class 1-3), did not. No other anaphylactic reactions were identified in any of the subjects exposed to rhC1INH. Analysis of post-exposure samples revealed that the risk of inducing new or boosting existing IgE responses to rabbit or cow's milk allergens was negligible. The propensity of rhC1INH to induce IgE antibodies following repeated administration of rhC1INH is low. Subjects with substantially elevated anti-rabbit epithelium IgE antibodies and/or clinical allergy to rabbits may have an increased risk for an allergic reaction. No other risk factors for allergic reactions to rhC1INH have been identified.

Occupational IgE sensitisation to phytase, a phosphatase derived from Aspergillus niger.

PubMed

Doekes, G; Kamminga, N; Helwegen, L; Heederik, D

1999-07-01

Phytase is a phosphatase derived from Aspergillus niger that enhances phosphate bioavailability in the gut, and therefore has been increasingly used as an animal feed additive since the early 1990s. The aim of this study was to assess whether work related respiratory symptoms among workers in a so called premix factory producing animal feed additives, could be due to type I (mediated by immunoglobulin E (IgE) allergic sensitisation to phytase. Preparations of specific IgE against phytase as used in the factory were assessed by enzyme immunoassay (EIA) in serum samples of 11 exposed workers who regularly handled the enzyme, in 11 office and laboratory workers of the same plant (non-exposed internal controls), and in 19 laboratory animal workers as external controls. The factory workers also completed a questionnaire on common and work related respiratory symptoms. Depending on the cut off level in the EIA for IgE, and the preparation used as coated allergen, antiphytase sensitisation was found in one to four of the 19 external controls, in one to five of the 11 internal controls, and in four to 10 of the 11 exposed workers. Strongest IgE reactions were found in four exposed workers who reported work related respiratory symptoms, particularly wheezing, and in one internal control who possibly had become sensitised because the structure of the factory building did not preclude airborne exposure in the offices and corridors of the plant. Experiments with inhibition EIA for IgE showed that (a) phytase of another commercial source was only partially cross reactive with phytase as used in the premix factory, and (b) phytase used as an animal feed additive did not cross react with common mould extracts, except for extracts from the species of origin, Aspergillus niger. The amount of IgE binding phytase in Aspergillus niger was estimated to be between 0.1% and 1% of the extractable mould proteins. Phytase is a potentially important new occupational allergen causing specific

Defining thresholds of specific IgE levels to grass pollen and birch pollen allergens improves clinical interpretation.

PubMed

Van Hoeyveld, Erna; Nickmans, Silvie; Ceuppens, Jan L; Bossuyt, Xavier

2015-10-23

Cut-off values and predictive values are used for the clinical interpretation of specific IgE antibody results. However, cut-off levels are not well defined, and predictive values are dependent on the prevalence of disease. The objective of this study was to document clinically relevant diagnostic accuracy of specific IgE for inhalant allergens (grass pollen and birch pollen) based on test result interval-specific likelihood ratios. Likelihood ratios are independent of the prevalence and allow to provide diagnostic accuracy information for test result intervals. In a prospective study we included consecutive adult patients presenting at an allergy clinic with complaints of rhinitis or rhinoconjunctivitis. The standard for diagnosis was a suggestive clinical history of grass or birch pollen allergy and a positive skin test. Specific IgE was determined with the ImmunoCAP Fluorescence Enzyme Immuno-Assay. We established specific IgE test result interval related likelihood ratios for clinical allergy to inhalant allergens (grass pollen, rPhl p 1,5, birch pollen, rBet v 1). The likelihood ratios for allergy increased with increasing specific IgE antibody levels. The likelihood ratio was <0.03 for specific IgE <0.1 kU/L, between 0.1 and 1.4 for specific IgE between 0.1 kU/L and 0.35 kU/L, between 1.4 and 4.2 for specific IgE between 0.35 kU/L and 3.5 kU/L, >6.3 for specific IgE>0.7, and very high (∞) for specific IgE >3.5 kU/L. Test result interval specific likelihood ratios provide a useful tool for the interpretation of specific IgE test results for inhalant allergens. Copyright © 2015 Elsevier B.V. All rights reserved.

IgE binding to peanut allergens is inhibited by combined D-aspartic and D-glutamic acids.

PubMed

Chung, Si-Yin; Reed, Shawndrika

2015-01-01

The objective of this study was to determine if D-amino acids (D-aas) bind and inhibit immunoglobulin E (IgE) binding to peanut allergens. D-aas such as D-Asp (aspartic acid), D-Glu (glutamic acid), combined D-[Asp/Glu] and others were each prepared in a cocktail of 9 other D-aas, along with L-amino acids (L-aas) and controls. Each sample was mixed with a pooled plasma from peanut-allergic donors, and tested by ELISA (enzyme-linked immunosorbent assay) and Western blots for IgE binding to peanut allergens. Results showed that D-[Asp/Glu] (4 mg/ml) inhibited IgE binding (75%) while D-Glu, D-Asp and other D-aas had no inhibitory effect. A higher inhibition was seen with D-[Asp/Glu] than with L-[Asp/Glu]. We concluded that IgE was specific for D-[Asp/Glu], not D-Asp or D-Glu, and that D-[Asp/Glu] was more reactive than was L-[Asp/Glu] in IgE inhibition. The finding indicates that D-[Asp/Glu] may have the potential for removing IgE or reducing IgE binding to peanut allergens in vitro. Published by Elsevier Ltd.

High-resolution crystal structure and IgE recognition of the major grass pollen allergen Phl p 3.

PubMed

Devanaboyina, S C; Cornelius, C; Lupinek, C; Fauland, K; Dall'Antonia, F; Nandy, A; Hagen, S; Flicker, S; Valenta, R; Keller, W

2014-12-01

Group 2 and 3 grass pollen allergens are major allergens with high allergenic activity and exhibit structural similarity with the C-terminal portion of major group 1 allergens. In this study, we aimed to determine the crystal structure of timothy grass pollen allergen, Phl p 3, and to study its IgE recognition and cross-reactivity with group 2 and group 1 allergens. The three-dimensional structure of Phl p 3 was solved by X-ray crystallography and compared with the structures of group 1 and 2 grass pollen allergens. Cross-reactivity was studied using a human monoclonal antibody which inhibits allergic patients' IgE binding and by IgE inhibition experiments with patients' sera. Conformational Phl p 3 IgE epitopes were predicted with the algorithm SPADE, and Phl p 3 variants containing single point mutations in the predicted IgE binding sites were produced to analyze allergic patients' IgE binding. Phl p 3 is a globular β-sandwich protein showing structural similarity to Phl p 2 and the Phl p 1-C-terminal domain. Phl p 3 showed IgE cross-reactivity with group 2 allergens but not with group 1 allergens. SPADE identified two conformational IgE epitope-containing areas, of which one overlaps with the epitope defined by the monoclonal antibody. The mutation of arginine 68 to alanine completely abolished binding of the blocking antibody. This mutation and a mutation of D13 in the predicted second IgE epitope area also reduced allergic patients' IgE binding. Group 3 and group 2 grass pollen allergens are cross-reactive allergens containing conformational IgE epitopes. They lack relevant IgE cross-reactivity with group 1 allergens and therefore need to be included in diagnostic tests and allergen-specific treatments in addition to group 1 allergens. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The property distance index PD predicts peptides that cross-react with IgE antibodies

PubMed Central

Ivanciuc, Ovidiu; Midoro-Horiuti, Terumi; Schein, Catherine H.; Xie, Liping; Hillman, Gilbert R.; Goldblum, Randall M.; Braun, Werner

2009-01-01

Similarities in the sequence and structure of allergens can explain clinically observed cross-reactivities. Distinguishing sequences that bind IgE in patient sera can be used to identify potentially allergenic protein sequences and aid in the design of hypo-allergenic proteins. The property distance index PD, incorporated in our Structural Database of Allergenic Proteins (SDAP, http://fermi.utmb.edu/SDAP/), may identify potentially cross-reactive segments of proteins, based on their similarity to known IgE epitopes. We sought to obtain experimental validation of the PD index as a quantitative predictor of IgE cross-reactivity, by designing peptide variants with predetermined PD scores relative to three linear IgE epitopes of Jun a 1, the dominant allergen from mountain cedar pollen. For each of the three epitopes, 60 peptides were designed with increasing PD values (decreasing physicochemical similarity) to the starting sequence. The peptides synthesized on a derivatized cellulose membrane were probed with sera from patients who were allergic to Jun a 1, and the experimental data were interpreted with a PD classification method. Peptides with low PD values relative to a given epitope were more likely to bind IgE from the sera than were those with PD values larger than 6. Control sequences, with PD values between 18 and 20 to all the three epitopes, did not bind patient IgE, thus validating our procedure for identifying negative control peptides. The PD index is a statistically validated method to detect discrete regions of proteins that have a high probability of cross-reacting with IgE from allergic patients. PMID:18950868

Fournier gangrene associated with hyper IgE syndrome (Job syndrome).

PubMed

Hori, Junichi; Yamaguchi, Satoshi; Watanabe, Masaki; Osanai, Hiroaki; Hori, Masako

2008-04-01

We report a case of a 32-year-old man with hyper IgE syndrome (Job syndrome) who developed Fournier gangrene due to infectious multiple atheromas of the scrotal skin that progressed to the right groin and thigh. The patient required surgical debridement and subsequent skin grafting. This is a rare case of Fournier gangrene associated with hyper IgE syndrome (Job syndrome). When a patient without diabetes mellitus has repeated infections and atopic-like dermatitis, Job syndrome should be considered.

Measurement of anti-Ascaris IgE antibody levels in tropical allergic patients, using modified ELISA.

PubMed

Lynch, N R; Pérez, M; López, R I; Turner, K J

1987-01-01

The two most common situations in which the determination of serum immunoglobulin E (IgE) levels is of interest are allergic disease and helminthic infection. This is of particular importance in the tropical environment, as helminthiasis possibly influences the expression of allergic reactivity. Because of the low absolute serum levels of IgE, solid-phase radioimmunoassay (RIA) is conventionally used for its measurement. The radioactive and toxic volatile reagents required restricted application of such assays in the tropical situation. We evaluated a nitrocellulose-based, avidin biotin-amplified enzyme-linked immunosorbent assay (ELISA) for IgE, in which monoclonal anti-IgE antibodies were employed. Excellent correlations were obtained between ELISA and RIA for both total and allergen-specific IgE measurement. The ELISA was then applied to determine the levels of anti-Ascaris antibodies in selected allergic patients, in whom no cutaneous immediate hypersensitivity reactions were demonstrated against common environmental allergens such as house dust, but who had positive skin reactions to Ascaris extract. When compared with non-allergic subjects who had equivalent cutaneous reactivity, no significant differences were found in total IgE levels, house-dust specific IgE levels or non-reaginic anti-Ascaris antibody levels. However, higher levels of IgE antibody against the parasite were detected in the allergic subjects. This observation raises the question of the possible role of Ascaris infection in the stimulation of allergic reactions in such patients. We describe an immunoenzymatic assay for total and specific IgE antibody that is better adapted to the tropical situation than the commonly used radioimmunoassays.(ABSTRACT TRUNCATED AT 250 WORDS)

Ana o 3-specific IgE is a good predictor for clinically relevant cashew allergy in children.

PubMed

Lange, L; Lasota, L; Finger, A; Vlajnic, D; Büsing, S; Meister, J; Broekaert, I; Pfannenstiel, C; Friedrichs, F; Price, M; Trendelenburg, V; Niggemann, B; Beyer, K

2017-04-01

Component-resolved diagnostics using specific IgE to 2 S albumins has shown to be a valuable new option in diagnostic procedure. Ana o 3 is a 2 S albumin from cashew. The aim of this study was to investigate the role of Ana o 3-specific serum IgE in the diagnosis of cashew allergy and to identify cut-off levels to replace oral food challenges. Moreover, the value of additional determination of total IgE has been investigated. In a multicentre study, we analysed specific IgE to cashew extract and Ana o 3 as well as total IgE in children with suspected cashew allergy using the ImmunoCAP-FEIA and a standardized diagnostic procedure including oral challenges where indicated. A total of 61 patients were included in the study. Forty-two were allergic to cashew, and 19 were tolerant. In receiver operating curves, Ana o 3 discriminates between allergic and tolerant children better than cashew-specific IgE with an area under the curve of 0.94 vs 0.78. The ratio of Ana o 3-specific IgE to total IgE did not further improve the diagnostic procedure. Probability curves for Ana o 3-specific IgE have been calculated, and a 95% probability could be estimated at 2.0 kU/l. Specific IgE to Ana o 3 is a valuable tool for the diagnosis of cashew allergy. Considering its positive predictive value, it might allow to make a considerable number of oral challenges superfluous. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

IGE AND IGGA ANTIBODY-MEDIATED RELEASE OF HISTAMINE FROM RAT PERITONEAL CELLS

PubMed Central

Bach, Michael K.; Bloch, Kurt J.; Austen, K. Frank

1971-01-01

IgGa, in contrast to IgE, antibodies mediated the antigen-induced release of histamine from rat peritoneal mast cells without a requirement for a latent period and without the capacity to bind firmly to the target cell. Nonetheless, IgGa anti-DNP antibody interfered with the capacity of rat anti-N. brasiliensis antiserum rich in IgE antibodies to prepare the target cells for histamine release by worm antigen. Further, interaction of IgE antibody-prepared cells with IgGa anti-DNP antibody and DNP-BSA at 0°C so as to achieve sterile activation, or at 30°C to permit histamine release, inactivated such cells as determined by the subsequent failure to release histamine upon challenge with worm antigen. Thus, although IgE and IgGa antibodies are immunochemically distinct homologous immunoglobulins and exhibit different functional characteristics, their interaction at the target cell involves a common receptor and at least one common point in the pathway to the release of pharmacologic agents from the cell. PMID:4101607

Serum IgE Concentration in Trisomy 21

ERIC Educational Resources Information Center

Lopez, Vicente

1974-01-01

Levels of serum IgE (an immunoglobulin carrying reaginic antibody activity) were investigated in 16 Down's syndrome adolescents (12-to 18-years old) and in an equal number of retardates matched for age and sex residing in the same institution. (CL)

Mast cells and IgE in defense against venoms: Possible "good side" of allergy?

PubMed

Galli, Stephen J; Starkl, Philipp; Marichal, Thomas; Tsai, Mindy

2016-01-01

Physicians think of mast cells and IgE primarily in the context of allergic disorders, including fatal anaphylaxis. This 'bad side' of mast cells and IgE is so well accepted that it can be difficult to think of them in other contexts, particularly those in which they may have beneficial functions. However, there is evidence that mast cells and IgE, as well as basophils (circulating granulocytes whose functions partially overlap with those of mast cells), can contribute to host defense as components of adaptive type 2 immune responses to helminths, ticks and certain other parasites. Accordingly, allergies often are conceptualized as "misdirected" type 2 immune responses, in which IgE antibodies are produced against any of a diverse group of apparently harmless antigens, as well as against components of animal venoms. Indeed, certain unfortunate patients who have become sensitized to venoms develop severe IgE-associated allergic reactions, including fatal anaphylaxis, upon subsequent venom exposure. In this review, we will describe evidence that mast cells can enhance innate resistance to reptile or arthropod venoms during a first exposure to such venoms. We also will discuss findings indicating that, in mice which survive an initial encounter with venom, acquired type 2 immune responses, IgE antibodies, the high affinity IgE receptor (FcɛRI), and mast cells can contribute to acquired resistance to the lethal effects of both honeybee venom and Russell's viper venom. These findings support the hypothesis that mast cells and IgE can help protect the host against venoms and perhaps other noxious substances. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Total serum IgE level influences oral food challenge tests for IgE-mediated food allergies.

PubMed

Horimukai, K; Hayashi, K; Tsumura, Y; Nomura, I; Narita, M; Ohya, Y; Saito, H; Matsumoto, K

2015-03-01

Probability curves predicting oral food challenge test (OFC) results based on specific IgE levels are widely used to prevent serious allergic reactions. Although several confounding factors are known to affect probability curves, the main factors that affect OFC outcomes are currently unclear. We hypothesized that an increased total IgE level would reduce allergic reactivity. Medical records of 337 and 266 patients who underwent OFCs for 3.5 g boiled hen's egg white and 3.1 ml raw cow's milk, respectively, were examined retrospectively. We subdivided the patients into three groups based on total IgE levels and age by percentile (<25th, 25-75th, and >75th percentiles), and logistic regression analyses were performed on each group. Patients with higher total IgE levels were significantly less responsive. In addition, age did not significantly affect the OFC results. Therefore, total IgE levels should be taken into account when predicting OFC results based on food-specific IgE levels. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Total IgE and eotaxin (CCL11) contents in tears of patients suffering from seasonal allergic conjunctivitis.

PubMed

Eperon, Simone; Berguiga, Marouen; Ballabeni, Pierluigi; Guex-Crosier, Catherine; Guex-Crosier, Yan

2014-09-01

To prospectively investigate patients with seasonal allergic conjunctivitis (SAC) during the pollen season and test associations between tears total IgE, eotaxin concentrations, and SAC severity. Enrolled patients presented ocular symptoms and clinical signs of SAC at the time of presentation. Ocular itching, hyperaemia, chemosis, eyelid swelling, and tearing were scored, and the sum of these scores was defined as the clinical score. Conjunctival papillae were separately graded. We measured eotaxin concentration in tears by an enzyme-linked immunosorbent assay (ELISA) and total tear IgE by Lacrytest strip. Among thirty patients (30 eyes), 11 showed neither tear IgE nor tear eotaxin, while 15 out of 19 patients with positive IgE values presented a positive amount of eotaxin in their tears (Fisher's test: p < 0.001). The mean eotaxin concentration was 641 ± 154 (SEM) pg/ml. In patients with no amount of tear IgE, we observed a lower conjunctival papilla grade than in patients whose tears contained some amount of IgE (trend test: p = 0.032). In the 15 patients whose tear eotaxin concentration was null, tear IgE concentration was 5.3 ± 3.5 arbitrary units; in the other 15 patients whose eotaxin was positive, IgE reached 21 ± 4.3 arbitrary U (Mann-Whitney: p < 0.001). We measured 127 ± 47 pg/ml eotaxin in patients with no history of SAC but newly diagnosed as suffering from SAC, and 852 ± 218 pg/ml eotaxin in patients with a known SAC (p = 0.008). In contrast, tear IgE concentrations of both groups did not differ statistically significantly (p = 0.947). If IgE and eotaxin secreted in tears are major contributors in SAC pathogenesis, they however act at different steps of the process.

An immunologically relevant rodent model demonstrates safety of therapy using a tumour-specific IgE.

PubMed

Josephs, Debra H; Nakamura, Mano; Bax, Heather J; Dodev, Tihomir S; Muirhead, Gareth; Saul, Louise; Karagiannis, Panagiotis; Ilieva, Kristina M; Crescioli, Silvia; Gazinska, Patrycja; Woodman, Natalie; Lomardelli, Cristina; Kareemaghay, Sedigeh; Selkirk, Christopher; Lentfer, Heike; Barton, Claire; Canevari, Silvana; Figini, Mariangela; Downes, Noel; Dombrowicz, David; Corrigan, Christopher J; Nestle, Frank O; Jones, Paul S; Gould, Hannah J; Blower, Philip J; Tsoka, Sophia; Spicer, James F; Karagiannis, Sophia N

2018-04-13

Designing biologically informative models for assessing the safety of novel agents, especially for cancer immunotherapy, carries substantial challenges. The choice of an in vivo system for studies on IgE antibodies represents a major impediment to their clinical translation, especially with respect to class-specific immunological functions and safety. Fcε receptor expression and structure are different in humans and mice, so that the murine system is not informative when studying human IgE biology. By contrast, FcεRI expression and cellular distribution in rats mirrors that of humans. We are developing MOv18 IgE, a human chimeric antibody recognizing the tumour-associated antigen folate receptor alpha. We created an immunologically congruent surrogate rat model likely to recapitulate human IgE-FcεR interactions, and engineered a surrogate rat IgE equivalent to MOv18. Employing this model, we examined in vivo safety and efficacy of anti-tumour IgE antibodies. In immunocompetent rats, rodent IgE restricted growth of syngeneic tumours in the absence of clinical, histopathological or metabolic signs associated with obvious toxicity. No physiological or immunological evidence of a 'cytokine-storm' or allergic response was seen, even at 50 mg/kg weekly doses. IgE treatment was associated with elevated serum concentrations of TNFα, a mediator previously linked with IgE-mediated anti-tumour and anti-parasitic functions, alongside evidence of substantially elevated tumoural immune cell infiltration and immunological pathway activation in tumour-bearing lungs. Our findings indicate safety of MOv18 IgE, in conjunction with efficacy and immune activation, supporting the translation of this therapeutic approach to the clinical arena. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Intrauterine sensitization of allergen-specific IgE analyzed by a highly sensitive new allergen microarray.

PubMed

Kamemura, Norio; Tada, Hitomi; Shimojo, Naoki; Morita, Yoshinori; Kohno, Yoichi; Ichioka, Takao; Suzuki, Koichi; Kubota, Kenji; Hiyoshi, Mineyoshi; Kido, Hiroshi

2012-07-01

To design a rational allergy prevention program, it is important to determine whether allergic sensitization starts in utero under the maternal immune system. To investigate the origin of allergen-specific IgE antibodies in cord blood (CB) and maternofetal transfer of immunoglobulins. The levels of food and inhalant allergen-specific IgE, IgA, IgG, and IgG(4) antibodies in CB and maternal blood (MB) from 92 paired neonates and mothers were measured by using a novel allergen microarray of diamond-like-carbon-coated chip, with high-sensitivity detection of allergen-specific antibodies and allergen profiles. The levels of allergen-specific IgE antibodies against food and inhalant allergens and allergen profiles were identical in CB and newborn blood, but the levels and profiles, specifically against inhalant allergens, were different from those in MB. The level of allergen-specific IgA antibodies was below the detection levels in CB despite clear detection in MB. Therefore, contamination with MB in CB was excluded on the basis of extremely low levels of IgA antibodies in CB and the obvious mismatch of the allergen-specific IgE and IgA profiles between CB and MB. However, the levels of allergen-specific IgG and IgG(4) antibodies and their allergen profiles were almost identical in both MB and CB. Allergen-specific levels of IgE and IgA antibodies and their allergen profiles analyzed by the diamond-like-carbon allergen chip indicate that IgE antibodies in CB are of fetal origin. Food-allergen specific IgE antibodies were detected more often than inhalant-allergen specific IgE antibodies in CB, the reason of which remains unclarified. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Detection of epsilon class switching and IgE synthesis in human B cells.

PubMed

Pène, Jérôme; Guilhot, Florence; Cognet, Isabelle; Guglielmi, Paul; Guay-Giroux, Angélique; Bonnefoy, Jean-Yves; Elson, Greg C; Yssel, Hans; Gauchat, Jean-François

2006-01-01

We observed that mast cells, as other cells expressing the CD40 ligand CD154, can trigger IgE synthesis in B cells in the presence of interleukin (IL)-4. Numerous complementary techniques can be used to follow the succession of molecular events leading to IgE synthesis. This chapter will illustrate how human B cells (naïve or memory) can be purified, stored, and cultivated in medium that is permissive for IgE synthesis and stimulated with IL-4 or IL-13 and CD40 activation, the latter being induced by soluble CD154, anti-CD40 antibodies, or CD154-expressing cells. All these molecules are expressed by mast cells. The quantification of the epsilon-sterile transcript synthesis by polymerase chain reaction or Northern blot, the epsilon excision circles produced during immunoglobulin heavy chain locus rearrangement by polymerase chain reaction, and the IgE production by enzyme-linked immunosorbent assay will be described.

Natural history of perceived food hypersensitivity and IgE sensitisation to food allergens in a cohort of adults.

PubMed

Patelis, Antonios; Gunnbjörnsdottir, Maria; Borres, Magnus P; Burney, Peter; Gislason, Thorarinn; Torén, Kjell; Forsberg, Bertil; Alving, Kjell; Malinovschi, Andrei; Janson, Christer

2014-01-01

No longitudinal studies exist on the natural history of food hypersensitivity and IgE sensitisation to food allergens in adults. To examine the natural history of food hypersensitivity, the natural history of IgE sensitisation to food allergens and to investigate the risk factors for new onset food hypersensitivity. Food hypersensitivity was questionnaire-assessed in 2307 individuals (aged 20-45 years) from Iceland and Sweden during the European Community Respiratory Health Survey both at baseline and follow-up 9 years later. IgE food and aeroallergen sensitisation were assessed in a subgroup of these individuals (n = 807). Values of 0.35 kU/L and above were regarded as positive sensitisation. Food hypersensitivity was reported by 21% of the subjects and this proportion remained unchanged at follow-up (p = 0.58). Fruits, nuts and vegetables were the three most common causes of food hypersensitivity, with a similar prevalence at baseline and follow-up. The prevalence IgE sensitisation to food allergens decreased in general by 56% (p<0.001) and IgE sensitisation to peanut decreased in particular by 67% (p = 0.003). The prevalence of timothy grass IgE sensitisation decreased by 15% (p = 0.003) while cat, mite and birch IgE sensitisation did not decrease significantly. Female sex, rhinitis, eczema and presence of IgE sensitisation to aeroallergens were independently associated with new onset food hypersensitivity. The prevalence of food hypersensitivity remained unchanged while the prevalence of IgE sensitisation to food allergens decreased in adults over a 9-year follow-up period. The decrease in prevalence of IgE sensitisation to food allergens was considerably larger than the change in prevalence of IgE sensitisation to aeroallergens.

Natural History of Perceived Food Hypersensitivity and IgE Sensitisation to Food Allergens in a Cohort of Adults

PubMed Central

Patelis, Antonios; Gunnbjörnsdottir, Maria; Borres, Magnus P.; Burney, Peter; Gislason, Thorarinn; Torén, Kjell; Forsberg, Bertil; Alving, Kjell

2014-01-01

Background No longitudinal studies exist on the natural history of food hypersensitivity and IgE sensitisation to food allergens in adults. Objective To examine the natural history of food hypersensitivity, the natural history of IgE sensitisation to food allergens and to investigate the risk factors for new onset food hypersensitivity. Methods Food hypersensitivity was questionnaire-assessed in 2307 individuals (aged 20–45 years) from Iceland and Sweden during the European Community Respiratory Health Survey both at baseline and follow-up 9 years later. IgE food and aeroallergen sensitisation were assessed in a subgroup of these individuals (n = 807). Values of 0.35 kU/L and above were regarded as positive sensitisation. Results Food hypersensitivity was reported by 21% of the subjects and this proportion remained unchanged at follow-up (p = 0.58). Fruits, nuts and vegetables were the three most common causes of food hypersensitivity, with a similar prevalence at baseline and follow-up. The prevalence IgE sensitisation to food allergens decreased in general by 56% (p<0.001) and IgE sensitisation to peanut decreased in particular by 67% (p = 0.003). The prevalence of timothy grass IgE sensitisation decreased by 15% (p = 0.003) while cat, mite and birch IgE sensitisation did not decrease significantly. Female sex, rhinitis, eczema and presence of IgE sensitisation to aeroallergens were independently associated with new onset food hypersensitivity. Conclusion The prevalence of food hypersensitivity remained unchanged while the prevalence of IgE sensitisation to food allergens decreased in adults over a 9-year follow-up period. The decrease in prevalence of IgE sensitisation to food allergens was considerably larger than the change in prevalence of IgE sensitisation to aeroallergens. PMID:24427301

An epigenome-wide association study of total serum IgE in Hispanic children.

PubMed

Chen, Wei; Wang, Ting; Pino-Yanes, Maria; Forno, Erick; Liang, Liming; Yan, Qi; Hu, Donglei; Weeks, Daniel E; Baccarelli, Andrea; Acosta-Perez, Edna; Eng, Celeste; Han, Yueh-Ying; Boutaoui, Nadia; Laprise, Catherine; Davies, Gwyneth A; Hopkin, Julian M; Moffatt, Miriam F; Cookson, William O C M; Canino, Glorisa; Burchard, Esteban G; Celedón, Juan C

2017-08-01

Total IgE is a therapeutic target in patients with allergic diseases. DNA methylation in white blood cells (WBCs) was associated with total IgE levels in an epigenome-wide association study of white subjects. Whether DNA methylation of eosinophils explains these findings is insufficiently understood. We tested for association between genome-wide DNA methylation in WBCs and total IgE levels in 2 studies of Hispanic children: the Puerto Rico Genetics of Asthma and Lifestyle Study (PR-GOAL; n = 306) and the Genes-environments and Admixture in Latino Americans (GALA II) study (n = 573). Whole-genome methylation of DNA from WBCs was measured by using the Illumina Infinium HumanMethylation450 BeadChip. Total IgE levels were measured by using the UniCAP 100 system. In PR-GOAL WBC types (ie, neutrophils, eosinophils, basophils, lymphocytes, and monocytes) in peripheral blood were measured by using Coulter Counter techniques. In the GALA II study WBC types were imputed. Multivariable linear regression was used for the analysis of DNA methylation and total IgE levels, which was first conducted separately for each cohort, and then results from the 2 cohorts were combined in a meta-analysis. CpG sites in multiple genes, including novel findings and results previously reported in white subjects, were significantly associated with total IgE levels. However, adjustment for WBC types resulted in markedly fewer significant sites. Top findings from this adjusted meta-analysis were in the genes ZFPM1 (P = 1.5 × 10 -12 ), ACOT7 (P = 2.5 × 10 -11 ), and MND1 (P = 1.4 × 10 -9 ). In an epigenome-wide association study adjusted for WBC types (including eosinophils), methylation changes in genes enriched in pathways relevant to asthma and immune responses were associated with total IgE levels among Hispanic children. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

High-Density IgE Recognition of the Major Grass Pollen Allergen Phl p 1 Revealed with Single-Chain IgE Antibody Fragments Obtained by Combinatorial Cloning

PubMed Central

Madritsch, Christoph; Gadermaier, Elisabeth; Roder, Uwe W.; Lupinek, Christian; Valenta, Rudolf; Flicker, Sabine

2015-01-01

The timothy grass pollen allergen Phl p 1 belongs to the group 1 of highly cross-reactive grass pollen allergens with a molecular mass of ~25–30 kDa. Group 1 allergens are recognized by >95% of grass pollen allergic patients. We investigated the IgE recognition of Phl p 1 using allergen-specific IgE-derived single-chain variable Ab fragments (IgE-ScFvs) isolated from a combinatorial library constructed from PBMCs of a grass pollen–allergic patient. IgE-ScFvs reacted with recombinant Phl p 1 and natural group 1 grass pollen allergens. Using synthetic Phl p 1–derived peptides, the binding sites of two ScFvs were mapped to the N terminus of the allergen. In surface plasmon resonance experiments they showed comparable high-affinity binding to Phl p 1 as a complete human IgE-derived Ab recognizing the allergens’ C terminus. In a set of surface plasmon resonance experiments simultaneous allergen recognition of all three binders was demonstrated. Even in the presence of the three binders, allergic patients’ polyclonal IgE reacted with Phl p 1, indicating high-density IgE recognition of the Phl p 1 allergen. Our results show that multiple IgE Abs can bind with high density to Phl p 1, which may explain the high allergenic activity and sensitizing capacity of this allergen. PMID:25637023

Serum Malassezia-specific IgE in dogs with recurrent Malassezia otitis externa without concurrent skin disease.

PubMed

Layne, Elizabeth A; DeBoer, Douglas J

2016-08-01

Immediate-type hypersensitivity (ITH), mediated by IgE, to Malassezia pachydermatis is recognized in atopic dogs with recurrent yeast dermatitis and otitis externa (OE). Malassezia-associated OE commonly occurs in dogs without other signs of atopic dermatitis (AD). The aim of this study was to detect Malassezia-specific IgE in the sera of dogs with recurrent Malassezia OE without concurrent skin disease. Sera from healthy dogs were used for comparison. An FcεRIα-based ELISA was used to measure Malassezia-specific IgE. There was no significant difference between number of positive affected dogs (6/21, 29%) and number of positive unaffected dogs (15/86, 17%) (P=0.36). There was also no significant difference in the concentrations of Malassezia-specific IgE between the two groups (P=0.97). Malassezia-specific IgE did not distinguish between patient groups so, as with other canine allergens, serum IgE reactivity for Malassezia could not be used to differentiate between diseased and healthy patients. The presence of Malassezia-specific IgE in some of the affected dogs might indicate ITH to Malassezia in those dogs. Evaluation of ITH via intradermal test reactivity and response to allergen-specific immunotherapy might clarify the role of Malassezia-associated ITH in similarly affected dogs. Copyright © 2016 Elsevier B.V. All rights reserved.

Inhibition of CD23-mediated IgE transcytosis suppresses the initiation and development of airway allergic inflammation

USDA-ARS?s Scientific Manuscript database

The epithelium lining the airway tract and allergen-specific IgE are considered essential controllers of inflammatory responses to allergens. The human IgE receptor, CD23 (Fc'RII), is capable of transporting IgE or IgE-allergen complexes across the polarized human airway epithelial cell (AEC) monola...

Persistence and evolution of allergen-specific IgE repertoires during subcutaneous specific immunotherapy

PubMed Central

Levin, Mattias; King, Jasmine J.; Glanville, Jacob; Jackson, Katherine J. L.; Looney, Timothy J.; Hoh, Ramona A.; Mari, Adriano; Andersson, Morgan; Greiff, Lennart; Fire, Andrew Z.; Boyd, Scott D.; Ohlin, Mats

2016-01-01

Background Specific immunotherapy (SIT) is the only treatment with proven long-term curative potential in allergic disease. Allergen-specific IgE is the causative agent of allergic disease, and antibodies contribute to SIT, but the effects of SIT on aeroallergen-specific B cell repertoires are not well understood. Objective To characterize the IgE sequences expressed by allergen-specific B cells, and track the fate of these B cell clones during SIT. Methods We have used high-throughput antibody gene sequencing and identification of allergen-specific IgE using combinatorial antibody fragment library technology to analyze immunoglobulin repertoires of blood and nasal mucosa of aeroallergen-sensitized individuals before and during the first year of subcutaneous SIT. Results Of 52 distinct allergen-specific IgE heavy chains from eight allergic donors, 37 were also detected by high-throughput antibody gene sequencing of blood, nasal mucosa, or both sample types. The allergen-specific clones had increased persistence, higher likelihood of belonging to clones expressing other switched isotypes, and possibly larger clone size than the rest of the IgE repertoire. Clone members in nasal tissue showed close mutational relationships. Conclusion Combining functional binding studies, deep antibody repertoire sequencing, and information on clinical outcomes in larger studies may in the future aid assessment of SIT mechanisms and efficacy. PMID:26559321

Combined effect of smoking habits and occupational exposure to hard metal on total IgE antibodies.

PubMed

Shirakawa, T; Kusaka, Y; Morimoto, K

1992-06-01

A survey was made within a population of workers (n = 706) exposed to hard metal dust (an alloy including cobalt), an agent known to cause occupational allergy. Twenty-seven (4 percent) of 733 workers were eliminated from consideration in this study because of atopic status identified prior to starting work in the plant. Using a Phadebas PRIST, the subjects' total IgE levels were determined and related to their smoking and exposure status. Nonexposed male smokers (n = 135) had a higher geometric mean IgE level (39.7 IU/ml) than did nonexposed subjects who had never smoked (33.1 IU/ml; n = 99); those with a higher Brinkman index (greater than 300), a smoking index obtained by multiplying the number of cigarettes per day by the duration of smoking in years, had significantly (p less than 0.05) decreased IgE levels. Although ex-smokers (n = 72) had a higher geometric mean IgE level (73.3 IU/ml) than did those who had never smoked, their serum IgE level declined with age since the time they quit smoking, regardless of their hard metal exposure status. Hard metal (cobalt) exposure may play a significant role as an adjuvant in the production of total IgE. A multivariate analysis demonstrated that hard metal exposure and a smoking habit together arithmetically (p less than 0.05) increased total IgE levels. These two factors may be preventable risk factors for occupational allergy in hard metal workers.

Use of Specific IgE and Skin Prick Test to Determine Clinical Reaction Severity

PubMed Central

Ta, Von; Weldon, Brittany; Yu, Grace; Humblet, Olivier; Neale-May, Susan; Nadeau, Kari

2012-01-01

Aims To determine whether specific IgE and skin prick test correlate better in predicting reaction severity during a double-blinded placebo controlled food challenge (DBPCFC) for egg, milk, and multiple tree nut allergens. Study design Prospective study. Place and Duration of Study Department of Pediatrics, Stanford University School of Medicine, August 2009 and ongoing. Methodology We examined the reaction severity of twenty-four subjects to nine possible food allergens: milk, egg, almond, cashew, hazelnut, peanut, sesame, pecan and walnut. Specific IgE and SPT were performed before each DBPCFC. DBPCFC results were classified into mild (1), moderate (2), or severe (3) reactions using a modified Bock’s criteria. Results Twenty four subjects underwent a total of 80 DBPCFC. Eighty percent of all DBPCFCs resulted in a positive reaction. A majority, 71%, were classified as mild. No reactions occurred with a SPT of zero mm while three reactions occurred with a negative specific IgE. All reactions were reversible with medication. Conclusion These data suggest that SPT and specific IgE levels are not associated with reaction severity (p<0.64 and 0.27, respectively). We also found that combining specific IgE and SPT improved specificity but did not help to achieve clinically useful sensitivity. For instance, an SPT > 5mm had a sensitivity of 91% and specificity of 50%. Combining SPT > 5mm and IgE > 7 resulted in a reduced sensitivity of 64%. Unexpectedly, a history of anaphylaxis 70% (n=17) was not predictive of anaphylaxis on challenge 4% (n=2). PMID:22993721

Quantitative measurement of IgE antibodies to purified allergens using streptavidin linked to a high-capacity solid phase.

PubMed

Erwin, Elizabeth A; Custis, Natalie J; Satinover, Shama M; Perzanowski, Matthew S; Woodfolk, Judith A; Crane, Julian; Wickens, Kristin; Platts-Mills, Thomas A E

2005-05-01

Commercially available assays for IgE antibody provide results in international units per milliliter for many allergen extracts, but this is not easily achieved with purified or novel allergens. To develop assays for IgE antibody suitable for purified or novel allergens by using a commercially available immunosorbent. Streptavidin coupled to a high-capacity immunosorbent (CAP) was used to bind biotinylated purified allergens from mite (Der p 1 and Der p 2), cat (Fel d 1), and dog (Can f 1). Assays for IgE antibody to these allergens were performed on sera from children (asthma and control) as well as adults with atopic dermatitis. The results were validated by serial dilution of sera with high and low levels of IgE antibody and were quantitated in international units per milliliter by using a standard curve. Values for IgE antibody to Der p 1, Der p 2, and Fel d 1 correlated with values obtained with the allergen extracts (r2 = 0.80, 0.84, and 0.95, respectively; P < .001 in each case). Furthermore, the values for IgE antibody in sera from children with high exposure to mite and cat allergens demonstrated 10-fold higher levels of IgE antibody to Der p 1 and Der p 2 than to Fel d 1 (P < .001). The streptavidin immunosorbent technique provides a new method for quantifying IgE antibody to purified proteins. The results provide evidence about the high quantities of IgE antibody to purified inhalant allergens in patients with atopic dermatitis. In addition, the results demonstrate major differences in IgE antibodies specific for mite and cat allergens among children with high exposure to both allergens.

Presence of functional, autoreactive human milk-specific IgE in infants with cow's milk allergy.

PubMed

Järvinen, K M; Geller, L; Bencharitiwong, R; Sampson, H A

2012-02-01

Occasionally, exclusively breastfed infants with cow's milk allergy (CMA) remain symptomatic despite strict maternal milk avoidance. To determine whether or not persistence of symptoms could be due to sensitization against endogenous human milk proteins with a high degree of similarity to bovine allergens. Ten peptides representing known bovine milk IgE-binding epitopes [α-lactalbumin (ALA), β- and κ-casein] and the corresponding, highly homologous human milk peptides were labelled with sera from 15 breastfed infants with CMA, aged 3 weeks to 12 months, and peptide (epitope)-specific IgE antibodies were assessed. Nine of the 15 breastfed infants became asymptomatic during strict maternal avoidance of milk and other major food allergens; six infants remained symptomatic until weaned. Ten older children, aged 5-15 years, with CMA were also assessed. The functional capacity of specific IgE antibodies was assessed by measuring β-hexosaminidase release from rat basophilic leukaemia cells passively sensitized and stimulated with human and bovine ALA. A minimum of one human milk peptide was recognized by IgE antibodies from 9 of 15 (60%) milk-allergic infants, and the majority of older children with CMA. Genuine sensitization to human milk peptides in the absence of IgE to bovine milk was occasionally seen. There was a trend towards specific IgE being detected to more human milk peptides in those infants who did not respond to the maternal milk elimination diet than in those who did (P = 0.099). Functional IgE antibody to human ALA was only detected in infants not responding to the maternal diet. Endogenous human milk epitopes are recognized by specific IgE from the majority of infants and children with CMA. Such autoreactive, human milk-specific IgE antibodies appear to have functional properties in vitro. Their role in provoking allergic symptoms in infants exclusively breastfed by mothers strictly avoiding dietary milk remains unclear. © 2011 Blackwell

Viewing a humorous film decreases IgE production by seminal B cells from patients with atopic eczema.

PubMed

Kimata, Hajime

2009-02-01

Sperms induced IgE production by seminal B cells from patients with atopic eczema via interaction of B cells with galectin-3 on sperms. We studied the effect of viewing a humorous film on IgE production by seminal B cells cultured with sperms. Twenty-four male patients with atopic eczema viewed a humorous film (Modern Times, featuring Charlie Chaplin). Just before and immediately after viewing, semen was collected, and seminal B cells and sperms were purified. Seminal B cells were cultured with sperms and IgE production was measured, while expression of galectin-3 on sperms was assessed. After viewing the humorous film, IgE production by B cells cultured with sperms was significantly decreased. Moreover, expression of galectin-3 on sperms was reduced. Viewing a humorous film reduced galectin-3 expression on sperms, which in turn decreased IgE production by seminal B cells cultured with sperms. These results indicate that viewing a humorous film may be helpful for the study and treatment of local IgE production and allergy in the reproductive tract.

IgE enhances Fc epsilon RI expression and IgE-dependent TNF-alpha release from canine skin mast cells.

PubMed

Brazís, P; De Mora, F; Ferrer, L; Puigdemont, A

2002-03-01

The role of IgE on mast cell (MC) activation is well known. Recent studies have demonstrated that IgE also has the ability to up-regulate the high affinity IgE receptor (Fc epsilon RI) on the surface of human and murine MC, leading to an increased production of cytokines and chemokines. In the present study, we have examined the influence of IgE levels on Fc epsilon RI expression, and its consequences on TNF-alpha production from canine skin MC. Mature MC were enzymatically dispersed from the skin biopsies of 6-8 dogs and were cultured for up to 5 days in medium supplemented with recombinant canine stem cell factor (SCF) (6 ng/ml), in the presence of increasing serum IgE concentrations (ranging from 0 to 80 microg/ml). Subsequently, skin MC were activated with anti-IgE, and TNF-alpha concentration was assessed 5h post-activation by a cytotoxic bioassay. Fc epsilon RI receptors were identified in MC surface by flow cytometry. MC cultured for up to 5 days in the presence of high serum IgE concentration (8 microg/ml) produced twice the quantity of TNF-alpha than MC cultured in the absence of serum IgE, in response to stimulation with anti-IgE. Moreover, the percentage of Fc epsilon RI-positive skin cells was found to be approximately double in cells cultured with serum IgE compared to that cultured in the absence of IgE, following saturation of IgE receptors. These results suggest that, as found in human and murine MC, IgE may induce an up-regulation of the Fc epsilon RI density and an enhancement in the secretory activity of canine skin MC. This study could be of great interest in designing new therapeutic strategies for controlling MC activation in inflammatory and allergic processes.

Different implications of paternal and maternal atopy for perinatal IgE production and asthma development.

PubMed

Wu, Chih-Chiang; Chen, Rong-Fu; Kuo, Ho-Chang

2012-01-01

Asthma is a hereditary disease associated with IgE-mediated reaction. Whether maternal atopy and paternal atopy have different impacts on perinatal IgE production and asthma development remains unclear. This paper reviews and summarizes the effects of maternal and paternal atopy on the developmental aspects of IgE production and asthma. Maternal atopy affects both pre- and postnatal IgE production, whereas paternal atopy mainly affects the latter. Maternally transmitted genes GSTP1 and FceRI-beta are associated with lung function and allergic sensitization, respectively. In IgE production and asthma development, the maternal influence on gene-environment interaction is greater than paternal influence. Maternal, paternal, and/or postnatal environmental modulation of allergic responses have been linked to epigenetic mechanisms, which may be good targets for early prevention of asthma.

Different Implications of Paternal and Maternal Atopy for Perinatal IgE Production and Asthma Development

PubMed Central

Wu, Chih-Chiang; Chen, Rong-Fu; Kuo, Ho-Chang

2012-01-01

Asthma is a hereditary disease associated with IgE-mediated reaction. Whether maternal atopy and paternal atopy have different impacts on perinatal IgE production and asthma development remains unclear. This paper reviews and summarizes the effects of maternal and paternal atopy on the developmental aspects of IgE production and asthma. Maternal atopy affects both pre- and postnatal IgE production, whereas paternal atopy mainly affects the latter. Maternally transmitted genes GSTP1 and FceRI-beta are associated with lung function and allergic sensitization, respectively. In IgE production and asthma development, the maternal influence on gene-environment interaction is greater than paternal influence. Maternal, paternal, and/or postnatal environmental modulation of allergic responses have been linked to epigenetic mechanisms, which may be good targets for early prevention of asthma. PMID:22272211

Increased IgE serum levels are unrelated to allergic and parasitic diseases in patients with juvenile systemic lupus erythematosus.

PubMed

Liphaus, Bernadete L; Jesus, Adriana A; Silva, Clovis A; Coutinho, Antonio; Carneiro-Sampaio, Magda

2012-11-01

The aim of this study was to assess the IgE serum levels in juvenile systemic lupus erythematosus patients and to evaluate possible associations with clinical and laboratory features, disease activity and tissue damage. The IgE serum concentrations in 69 consecutive juvenile systemic lupus erythematosus patients were determined by nephelometry. IgG, IgM and IgA concentrations were measured by immunoturbidimetry. All patients were negative for intestinal parasites. Statistical analysis methods included the Mann-Whitney, chi-square and Fisher's exact tests, as well as the Spearman rank correlation coefficient. Increased IgE concentrations above 100 IU/mL were observed in 31/69 (45%) juvenile systemic lupus erythematosus patients. The mean IgE concentration was 442.0 ± 163.4 IU/ml (range 3.5-9936.0 IU/ml). Fifteen of the 69 patients had atopic disease, nine patients had severe sepsis and 56 patients presented with nephritis. The mean IgE level in 54 juvenile systemic lupus erythematosus patients without atopic manifestations was 271.6 ± 699.5 IU/ml, and only nine of the 31 (29%) patients with high IgE levels had atopic disease. The IgE levels did not statistically differ with respect to the presence of atopic disease, severe sepsis, nephritis, disease activity, or tissue damage. Interestingly, IgE concentrations were inversely correlated with C4 levels (r = -0.25, p = 0.03) and with the SLICC/ACR-DI score (r = -0.34, p = 0.005). The IgE concentration was also found to be directly correlated with IgA levels (r = 0.52, p = 0.03). The present study demonstrated for the first time that juvenile systemic lupus erythematosus patients have increased IgE serum levels. This increase in IgE levels was not related to allergic or parasitic diseases. Our results are in line with the hypothesis that high IgE levels can be considered a marker of immune dysregulation.

Comparison of serum concentrations of environmental allergen-specific IgE in atopic and healthy (nonatopic) horses.

PubMed

Wilkołek, P; Sitkowski, W; Szczepanik, M; Adamek, Ł; Pluta, M; Taszkun, I; Gołyński, M; Malinowska, A

2017-12-01

Allergic responses in humans, horses and other species are mediated by immunoglobulin E (IgE) antibodies. Serum testing to detect allergen-specific IgE antibodies has been developed for dogs, cats and horses; this allows for the identification of allergens and determination of appropriate allergen- specific immunotherapies. This study compared serum allergen-specific IgE concentrations in atopic and healthy horses. The study was performed on Malopolski breed atopic (n=21) and nonatopic (n=21) clinically healthy horses. Allergen-specific IgE serum concentrations were measured in summer seasons of 2008-2015 using a monoclonal anti-IgE antibody. A Northern and Central European allergen panel containing mite, insect, mould and plant pollen allergens, including 15 tests of individual allergens and 5 tests of allergen mixtures was used. The mean allergen-specific IgE concentrations in the atopic and normal horse populations were compared. Among the atopic horses, the strongest positive reactions occurred against the storage mites Tyrophagus putrescentiae and the domestic mite Dermatophagoides farinae. The atopic horses also demonstrated high IgE concentrations against insects, particularly Tabanus sp., the plant pollens colza, cultivated rye and the mould pollen mixture Aspergillus/Penicillium. No horses in the atopic group were IgE-negative. Among all mite, insect, mould and some plant allergen groups the differences in mean specific IgE concentrations between allergic and healthy horses were significant. The mean IgE concentrations for most allergen groups were significantly higher in the atopic horses than in the healthy animals. However, a high incidence of positive reactions was observed in both healthy and allergic horses. Our results showed a high frequency of polysensitization in atopic horses. Copyright© by the Polish Academy of Sciences.

Computationally predicted IgE epitopes of walnut allergens contribute to cross-reactivity with peanuts

USDA-ARS?s Scientific Manuscript database

Cross reactivity between peanuts and tree nuts implies that similar IgE epitopes are present in their proteins. To determine whether walnut sequences similar to known peanut IgE binding sequences, according to the property distance (PD) scale implemented in the Structural Database of Allergenic Prot...

Quantitative assessment of serum-specific IgE in the diagnosis of human cystic echinococcosis.

PubMed

Marinova, I; Nikolov, G; Michova, A; Kurdova, R; Petrunov, B

2011-07-01

Anti-Echinococcus serum immunoglobulin (Ig)E was assessed by the ImmunoCAP system and compared with anti-Echinococcus serum IgG assessed by enzyme-linked immunosorbent assay (ELISA) and Western blot. The ImmunoCAP system revealed very high specificity (one false positive of 110 healthy individuals), low cross-reactivity (one false positive of 58 patients with other diseases) and decreased sensitivity (73.55%). Receiver operating characteristic analysis displayed a beneficial diagnostic value with high accuracy. Comparison of the ImmunoCAP system with ELISA and Western blot showed significantly higher specificity and significantly lower cross-reactivity compared with the ELISA. Examination of sera from 155 patients with cystic echinococcosis (CE) showed varying levels of anti-Echinococcus IgE (range, 0.01-118.33 kUA/L). However, most samples had moderately elevated IgE levels. Analysis of serum-specific IgE revealed significantly higher sensitivity of the ImmunoCAP system and significantly higher antibody levels in hepatic CE compared with pulmonary CE. © 2011 Blackwell Publishing Ltd.

Expression and biological effects of high levels of serum IgE in epsilon heavy chain transgenic mice.

PubMed

Adamczewski, M; Köhler, G; Lamers, M C

1991-03-01

We have generated and examined transgenic mice carrying a rearranged immunoglobulin transgene coding for the heavy chain of an IgE antibody. These mice produce the secreted form of the recombinant epsilon heavy chain. Serum IgE levels were increased at least 100-fold over control values. Transgenic epsilon mRNA was detected in spleen and thymus, not in liver and heart. Transgenic epsilon production in vitro was slightly up-regulated by T cells, but not affected by interleukin 4 in vitro or Nippostrongylus infestation in vivo. The B cell and T cell compartments and antigen-specific IgE, IgG1 and IgM responses as well as the increase in endogenous IgE after Nippostrongylus infestation in transgenic mice were normal. These data indicate that the presence of high levels of transgenic IgE did not induce class-specific suppressive mechanisms. Transgenic IgE bound to Fc epsilon receptor type I and Fc epsilon receptor type II and mediated histamine release from mast cells in vitro and an allergic skin reaction in vivo. It inhibited an ovalbumin-specific skin reaction in ovalbumin-immunized transgenic mice only during the initial phases of the immune response. This result has a bearing on the feasibility of immune therapy of allergic diseases with substances that block binding of IgE to its receptors.

Dysbiosis of Inferior Turbinate Microbiota Is Associated with High Total IgE Levels in Patients with Allergic Rhinitis.

PubMed

Hyun, Dong-Wook; Min, Hyun Jin; Kim, Min-Soo; Whon, Tae Woong; Shin, Na-Ri; Kim, Pil Soo; Kim, Hyun Sik; Lee, June Young; Kang, Woorim; Choi, Augustine M K; Yoon, Joo-Heon; Bae, Jin-Woo

2018-04-01

Abnormalities in the human microbiota are associated with the etiology of allergic diseases. Although disease site-specific microbiota may be associated with disease pathophysiology, the role of the nasal microbiota is unclear. We sought to characterize the microbiota of the site of allergic rhinitis, the inferior turbinate, in subjects with allergic rhinitis ( n = 20) and healthy controls ( n = 12) and to examine the relationship of mucosal microbiota with disease occurrence, sensitized allergen number, and allergen-specific and total IgE levels. Microbial dysbiosis correlated significantly with total IgE levels representing combined allergic responses but not with disease occurrence, the number of sensitized allergens, or house dust mite allergen-specific IgE levels. Compared to the populations in individuals with low total IgE levels (group IgE low ), low microbial biodiversity with a high relative abundance of Firmicutes phylum ( Staphylococcus aureus ) and a low relative abundance of Actinobacteria phylum ( Propionibacterium acnes ) was observed in individuals with high total serum IgE levels (group IgE high ). Phylogeny-based microbial functional potential predicted by the 16S rRNA gene indicated an increase in signal transduction-related genes and a decrease in energy metabolism-related genes in group IgE high as shown in the microbial features with atopic and/or inflammatory diseases. Thus, dysbiosis of the inferior turbinate mucosa microbiota, particularly an increase in S. aureus and a decrease in P. acnes , is linked to high total IgE levels in allergic rhinitis, suggesting that inferior turbinate microbiota may be affected by accumulated allergic responses against sensitized allergens and that site-specific microbial alterations play a potential role in disease pathophysiology. Copyright © 2018 American Society for Microbiology.

The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response

USDA-ARS?s Scientific Manuscript database

The mechanisms involved in the maintenance of memory IgE responses are poorly understood, and the role played by germinal center (GC) IgE+ cells in memory responses is particularly unclear. IgE B cell differentiation is characterized by a transient GC phase, a bias towards the plasma cell (PC) fate,...

Application Protocol, Initial Graphics Exchange Specification (IGES), Layered Electrical Product

DOE Office of Scientific and Technical Information (OSTI.GOV)

O`Connell, L.J.

1994-12-01

An application protocol is an information systems engineering view of a specific product The view represents an agreement on the generic activities needed to design and fabricate the product the agreement on the information needed to support those activities, and the specific constructs of a product data standard for use in transferring some or all of the information required. This application protocol describes the data for electrical and electronic products in terms of a product description standard called the Initial Graphics Exchange Specification (IGES). More specifically, the Layered Electrical Product IGES Application Protocol (AP) specifies the mechanisms for defining andmore » exchanging computer-models and their associated data for those products which have been designed in two dimensional geometry so as to be produced as a series of layers in IGES format The AP defines the appropriateness of the data items for describing the geometry of the various parts of a product (shape and location), the connectivity, and the processing and material characteristics. Excluded is the behavioral requirements which the product was intended to satisfy, except as those requirements have been recorded as design rules or product testing requirements.« less

Age-dependent modulation of serum IgE and mast cell sensitization by Nippostrongylus brasiliensis infestation in rats.

PubMed

Turner, K J; Fisher, E H; Mayrhofer, G

1981-08-01

The capacity of N. brasiliensis (Nb) infestation to modify synthesis of ovalbumin (OV) specific IgE antibody was monitored in weanling, juvenile and adult female WAG rats by both passive cutaneous anaphylaxis (PCA) activity and by a rat radio-allergosorbent test (RAST). Infestation with Nb larvae 10 days after immunization with OV produced marginal potentiation of anti-OV Ig antibody production by both RAST and PCA in weanlings, marginal suppression by both parameters in juveniles and was without effect in adults. However, immunization with OV after infestation with Nb partially suppressed anti-OV IgE antibody production in weanlings (RAST) and totally abolished the PCA activity. Although this regime did not impair anti-OV IgE antibody synthesis (RAST) in juveniles, the sera were PCA-negative. In contrast, normal responses were found in adult rats. Negative PCA titres in sera containing high levels of specific antibody occurred when serum total IgE levels were elevated, and are explained on the basis of competition for binding sites on mast cells. The ratio of OV-specific IgE to 'total' IgE is a critical factor in detecting PCA activity.

CLINICALLY RELEVANT IGE-CROSS-REACTIVITY OF NUT ALLERGENS

EPA Science Inventory

All data resulting from this study will be catalogued in SDAP .This work will generate important information relating the structure/ physicochemical properties of cross-reactive IgE epitopes to clinical response, and model factors that underlie allergen recognition by the immu...

Prevalence of IgE against neuromuscular blocking agents in hairdressers and bakers.

PubMed

Dong, S; Acouetey, D S; Guéant-Rodriguez, R-M; Zmirou-Navier, D; Rémen, T; Blanca, M; Mertes, P M; Guéant, J-L

2013-11-01

Allergic IgE-mediated reactions to neuromuscular blocking agents (NMBAs) are the main cause of immediate hypersensitivity reactions in anaesthesia; their predominant occurrence in the absence of previous exposure to NMBAs suggests a risk related to environmental exposure. To investigate the prevalence of specific IgE to quaternary ammonium ions in two populations professionally exposed to quaternary ammonium compounds, in the north-eastern France. The study had a retrospective follow-up design whereby apprentices were assessed after their 2-year training period as apprentices. The professionally exposed hairdresser populations (n = 128) were compared with baker/pastry makers (n = 108) and 'non-exposed' matched control subjects (n = 379). We observed a 4.6-fold higher frequency of positive IgE against quaternary ammonium ions in hairdressers (HD), compared with baker/pastry makers (BP) and control (C) groups. The competitive inhibition of quaternary ammonium Sepharose radioimmunoassay (QAS-IgE RIA) with succinylcholine was significantly higher in HD, compared with BP and C groups, with inhibition percentage of 66.2 ± 7.4, 39.7 ± 6.0 and 43.8 ± 9.9, respectively (P < 0.001). The specific IgE against quaternary ammonium ions recognized also two compounds widely used by hairdressers, benzalkonium chloride and polyquaternium-10, in competitive inhibition of IgE RIA. When considering the whole study population, hairdresser professional exposure and total IgE > 100 kU/L were the two significant predictors of IgE-sensitization against quaternary ammonium ions in the multivariate analysis of a model that included age, sex, professional exposure, increased concentration of total IgE (IgE > 100 kU/L) and positive IgE against prevalent allergens (Phadiatop(®) ; P = 0.019 and P = 0.001, respectively). The exposure to hairdressing professional occupational factors increases IgE-sensitization to NMBAs and quaternary ammonium ion compounds used in

The β2-adrenoreceptor gene promoter polymorphisms may modulate β2-agonist- and glucocorticoid-induced IgE synthesis.

PubMed

Chalubinski, M; Grzegorczyk, J; Grzelak, A; Jarzebska, M; Kowalski, M L

2014-01-01

β2-adrenoreceptor (β2-AR) agonists and glucocorticoids (GCS) were shown to induce IgE synthesis in human PBMCs. Serum total IgE levels are associated with single nucleotide polymorphisms (SNPs) of the β2-AR gene. We aimed to assess the association of the effect of fenoterol (β2-AR agonist) on IL-4-driven and budesonide-induced IgE synthesis with genetic variants of β2-AR. The study included 25 individuals: 13 with allergic asthma and/or allergic rhinitis and 12 healthy volunteers. PBMCs were cultured with IL-4, fenoterol and/or budesonide, and IgE concentrations in supernatants were assessed. Five SNPs in positions: -47, -20, 46, 79 and 252 of β2-AR were determined by direct DNA sequencing. In -47 T/T and -20 T/T patients, incubation with fenoterol resulted in decreased IgE production, whereas in -47 C/T and -47 C/C as well as in -20 C/T and -20 C/C individuals, it was enhanced. In contrast to fenoterol, budesonide-induced IgE synthesis was significantly increased in -47 T/T and -20 T/T patients as compared to -47 C/T, -47 C/C, -20 C/T and -47 C/C individuals. Polymorphisms in positions 46, 79 and 252 were not associated with fenoterol- or budesonide-modulated IgE synthesis. No differences in the distribution of IgE synthesis was seen between atopic and non-atopic individuals carrying the same alleles. The differential effect of β2-agonists and GCS on IgE synthesis may be associated with genetic variants of promoter region of the β2-AR gene. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

Natural clinical tolerance to peanut in African patients is caused by poor allergenic activity of peanut IgE.

PubMed

Wollmann, E; Hamsten, C; Sibanda, E; Ochome, M; Focke-Tejkl, M; Asarnoj, A; Önell, A; Lilja, G; Gallerano, D; Lupinek, C; Thalhamer, T; Weiss, R; Thalhamer, J; Wickman, M; Valenta, R; van Hage, M

2015-06-01

In Africa, peanuts are frequently consumed, but severe allergic reactions are rare. We investigated immunological patterns of clinical tolerance to peanut in peanut-sensitized but asymptomatic patients from central Africa compared to peanut-allergic and peanut-sensitized but asymptomatic patients from Sweden. Sera from allergic patients (n = 54) from Zimbabwe sensitized to peanut but without allergic symptoms to peanut, and sera from peanut-allergic (n = 25) and peanut-sensitized but asymptomatic (n = 25) patients from Sweden were analyzed toward peanut allergen components (Ara h 1-3, 6, 8-9) and other allergen molecules from important allergen sources using microarray. IgE to Ara h 2 peptide epitopes was analyzed, and allergenic activity was assessed by basophil activation assay. Forty-six percent of the African and all peanut-allergic Swedish patients showed IgE toward one of the highly allergenic peanut allergens (Ara h 1-3, 6, 9). However, 48% of the African patients had IgE to cross-reactive carbohydrate determinants (CCDs) with low allergenic activity and 60% of the Swedish asymptomatic patients had IgE against the PR protein Ara h 8. IgG and IgG4 specificities and levels could not discriminate between the African asymptomatic and Swedish peanut-allergic patients. Asymptomatic patients almost lacked IgE to Ara h 2 peptides, which were recognized by peanut-allergic patients. Peanut IgE from peanut asymptomatic patients showed poor allergenic activity compared with IgE from peanut-allergic patients. Natural clinical tolerance to peanut in the African patients can be caused by IgE to low allergenic peanut components and by poor allergenic activity of peanut-specific IgE. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of filgrastim (recombinant human granulocyte colony stimulating factor) on IgE responses in human asthma: a case study.

PubMed

Smith-Norowitz, Tamar A; Joks, Rauno; Norowitz, Kevin B; Chice, Seto; Durkin, Helen G; Bluth, Martin H

2013-10-01

The role of peripheral blood progenitor cell mobilization on Immunoglobulin E (IgE) responses has not been studied. Distributions of blood lymphocytes (CD4+, CD8+, CD8+CD60+, CD19+, CD23+, CD16/56+, CD25, CD45RA+, CD45RO+, CD34+), and levels of serum immunoglobulins (IgM, IgG, IgA, IgE) were studied in an allergic asthmatic serum IgE+ (181IU/mL) adult (m/45 y/o) donor undergoing routine stem cell mobilization protocol (American Society of Hematology) before (day-30), during (day 4), and after (1 wk post last dose) filgrastim (subcutaneous, 480 mcg, 2qd) treatment (flow cytometry, nephelometry, UniCAP Total IgE Fluoro enzyme immunoassay). On day 4 of filgrastim treatment, numbers of CD8+CD60+T cells and CD23+ blood cells dramatically increased (98% and 240% respectively) compared with pre treatment. In contrast on day 4 of treatment, serum IgE levels decreased (>50%) compared with pre treatment. CD8+CD60+T cells and CD23+ blood cells and serum IgE levels approached pre-treatment levels at 1 week post treatment. Filgrastim treatment transiently increases numbers of CD8+CD60+T and CD23+ expressing cells, which are known to regulate human IgE responses, while also transiently suppressing ongoing IgE responses. These results suggest that filgrastim affects IgE related responses, and may be useful in modulating allergic responses. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparison between sensitivity of autologous skin serum test and autologous plasma skin test in patients with Chronic Idiopathic Urticaria for detection of antibody against IgE or IgE receptor (FcεRIα).

PubMed

Sajedi, Vahid; Movahedi, Masoud; Aghamohammadi, Asghar; Aghamohamadi, Asghar; Gharagozlou, Mohammad; Ghareguzlou, Mohammad; Shafiei, Alireza; Soheili, Habib; Sanajian, Nahal

2011-06-01

Intradermal injection of autologous serum and plasma elicit a cutaneous reactivity in almost 45-60% of patients with Chronic Idiopathic Urticaria (CIU). This reactivity is associated with the presence of auto antibodies against IgE or IgE receptors. This study was carried out to compare the cutaneous reactivity of autologous serum and plasma skin tests in a series of patients with CIU for diagnosis of auto antibodies against IgE or IgE receptor. Fifty eight patients with CIU were injected intradermally with autologous serum and plasma (anticoagulated by citrate). Histamine was used as positive control and normal saline as negative control. The study group was checked by routine laboratory tests (CBC, U/A etc), allergens with skin prick tests, and serum IgE level, and auto antibodies against thyroid as well. Duration of urticaria was another factor which was assessed.There was no significant difference between positive ASST and positive APST patients for the above mentioned tests. 77.6% of the patients were Positive for APST and 65.5% were ASST positive. Duration of urticaria was longer in patients with positive ASST and APST than ASST and APST negative patients, although the difference was not statistically significant.Autologus serum skin test (ASST) and autologous plasma skin test (APST) could be used for estimation of duration and severity of urticaria and planning for the treatment.

Effect of Proteolysis with Alkaline Protease Following High Hydrostatic Pressure Treatment on IgE Binding of Buckwheat Protein.

PubMed

Lee, Chaeyoon; Lee, Wonhui; Han, Youngshin; Oh, Sangsuk

2017-03-01

Buckwheat is a popular food material in many Asian countries and it contains major allergenic proteins. This study was performed to analyze the effects of hydrolysis with alkaline protease following high hydrostatic pressure (HHP) treatment on the IgE binding of buckwheat protein. Extracted buckwheat protein was treated with HHP at 600 MPa for 30 min and hydrolyzed with alkaline protease for 240 min. IgE binding was examined using an enzyme-linked immunosorbent assay (ELISA) with serum samples from 14 patients who were allergic to buckwheat. Depending on the serum samples, HHP treatment of buckwheat protein without enzymatic hydrolysis decreased the IgE binding by 8.9% to 73.2% or increased by 31% to 78%. The IgE binding of buckwheat protein hydrolyzed with alkaline protease decreased by 73.8% to 100%. The IgE binding of buckwheat protein hydrolyzed with alkaline protease following HHP treatment decreased by 83.8% to 100%. This suggested that hydrolysis with alkaline protease following HHP treatment could be applied to reduce the IgE binding of buckwheat protein. © 2017 Institute of Food Technologists®.

Total IgE and Asthma Prevalence in the U.S. Population: Results from the National Health and Nutrition Examination Survey (NHANES) 2005–2006

PubMed Central

Gergen, Peter J.; Arbes, Samuel J.; Calatroni, Agustin; Mitchell, Herman E.; Zeldin, Darryl C.

2009-01-01

Background The inability to measure IgE-based sensitivity to all allergens has limited our understanding of what portion of asthma is related to IgE. Total IgE can potentially overcome this limitation. Objective Determine the association between total IgE and asthma Methods The National Health and Nutrition Examination Survey (NHANES) 2005–2006 examined a representative sample of the U.S. population 6 years of age and older. Results The median total IgE was 40.8 kU/L (IQR 15.5 – 114). Total IgE levels varied with age, sex, race/ethnicity, serum cotinine, body size, and socioeconomic status. The prevalence of current asthma was 8.8%. The prevalence of atopy was 42.5% as defined by 15 specific IgEs. The adjusted odds ratio (OR) for asthma with a 10-fold increase in total IgE was 2.18 (95% CI: 1.66–2.87). Total IgE predicted asthma only among atopics OR = 2.41 (95% CI: 1.62–3.60) not non-atopics OR = 1.11 (95% CI: 0.72–1.71) (interaction p=0.005). Among atopics, the association between total IgE and asthma became stronger as the number of positive specific IgE tests increased. Asthma was present at even the lowest levels of total IgE, regardless of atopic status. Approximately 92% of atopics were identified by six specific IgEs, but to increase the identification to over 99% required 11 specific IgEs. Conclusion Total IgE is associated with asthma only among persons who are positive to at least one allergen-specific IgEs. Asthma independent of IgE is not uncommon in the US populations. The complete identification of atopics in a population requires a large panel of allergen-specific IgEs. PMID:19647861

Hyper IgE in Childhood Eczema and Risk of Asthma in Chinese Children.

PubMed

Ng, Chantel; Hon, Kam Lun; Kung, Jeng Sum Charmaine; Pong, Nga Hin; Leung, Ting-Fan; Wong, Chun Kwok

2016-06-10

Atopic eczema is a common childhood disease associated with high IgE and eosinophilia. We characterized the clinical features associated with hyper-IgE (defined as IgE > 2000 IU/L) in eczema. Nottingham Eczema Severity Score (NESS), family and personal history of atopy, skin prick test (SPT) for common food and aeroallergens, highest serum IgE ever and eosinophil counts were evaluated in 330 children eczema patients. Childhood-NESS (NESS performed at <10 years of age) and adolescent-NESS (NESS performed at >10 years of age) were further analyzed. IgE correlated with NESS (spearman coefficient 0.35, p < 0.001) and eosinophil percentage (spearman coefficient 0.56, p = 0.001). Compared with IgE ≤ 2000IU/L (n = 167), patients with hyper-IgE (n = 163) were associated with male gender (p = 0.002); paternal atopy (p = 0.026); personal history of atopic rhinitis (p = 0.016); asthma (p < 0.001); dietary avoidance (p < 0.001); use of wet wrap (p < 0.001); traditional Chinese medicine use (TCM, p < 0.001); immunomodulant use (azathioprine or cyclosporine, p < 0.001); skin prick sensitization by dust mites (p < 0.001), cats (p = 0.012), dogs (p = 0.018), food (p = 0.002); eosinophilia (p < 0.001); more severe disease during childhood (p < 0.0001) and during adolescence (p < 0.0001), but not onset age of eczema or maternal atopy. Logistic regression showed that hyper-IgE was associated with personal history of asthma (exp(B) = 5.12, p = 0.002) and eczema severity during childhood and adolescence (p < 0.001). For patients <10 years of age, dust mite sensitization (p = 0.008) was associated with hyper-IgE. For patients >10years of age, food allergen sensitization was associated with hyper-IgE (p = 0.008). Hyper-IgE is independently associated with asthma, more severe atopy and more severe eczema during childhood and adolescence. IgE > 2000 IU/L may be a tool to aid prognostication of this chronic relapsing dermatologic disease and its progression to asthma.

Presence of functional, autoreactive human milk-specific IgE in infants with cow’s milk allergy

PubMed Central

Järvinen, K. M.; Geller, L.; Bencharitiwong, R.; Sampson, H. A.

2013-01-01

Summary Background Occasionally, exclusively breastfed infants with cow’s milk allergy (CMA) remain symptomatic despite strict maternal milk avoidance. Objective To determine whether or not persistence of symptoms could be due to sensitization against endogenous human milk proteins with a high degree of similarity to bovine allergens. Methods Ten peptides representing known bovine milk IgE-binding epitopes [α-lactalbumin (ALA), β- and κ-casein] and the corresponding, highly homologous human milk peptides were labelled with sera from 15 breastfed infants with CMA, aged 3 weeks to 12 months, and peptide (epitope)-specific IgE antibodies were assessed. Nine of the 15 breastfed infants became asymptomatic during strict maternal avoidance of milk and other major food allergens; six infants remained symptomatic until weaned. Ten older children, aged 5–15 years, with CMA were also assessed. The functional capacity of specific IgE antibodies was assessed by measuring β-hexosaminidase release from rat basophilic leukaemia cells passively sensitized and stimulated with human and bovine ALA. Results A minimum of one human milk peptide was recognized by IgE antibodies from 9 of 15 (60%) milk-allergic infants, and the majority of older children with CMA. Genuine sensitization to human milk peptides in the absence of IgE to bovine milk was occasionally seen. There was a trend towards specific IgE being detected to more human milk peptides in those infants who did not respond to the maternal milk elimination diet than in those who did (P = 0.099). Functional IgE antibody to human ALA was only detected in infants not responding to the maternal diet. Conclusions and Clinical Relevance Endogenous human milk epitopes are recognized by specific IgE from the majority of infants and children with CMA. Such autoreactive, human milk-specific IgE antibodies appear to have functional properties in vitro. Their role in provoking allergic symptoms in infants exclusively breastfed by

The relationship of the p–k titre to the serum ige level in patients with leprosy

PubMed Central

Hamburger, R. N.; Fernandez-Cruz, E.; Arnaiz, A.; Perez, B.; Bootello, A.

1974-01-01

Fifty patients with leprosy were found to have P–K titres inversely related to their serum IgE levels. Patients with leprosy react in a manner similar to normal individuals and to patients with other diseases. Serum IgG, IgM, IgA and complement were measured in twenty-five of the leprosy patients in addition to the serum IgE and only the IgG significantly positively correlated with the serum IgE. All of these leprosy patients were shown to react to exogenous histamine and they released endogenous histamine when chemically stimulated. Two patients had absent flare responses with normal weals, the remaining forty-eight had complete weal and flare responses. Higher serum IgE levels were noted in those patients with recent institution of chemotherapy. PMID:4143279

Suppressive effect of ethanol extract from mango (Mangifera indica L.) peel on IgE production in vitro and in vivo.

PubMed

Ishida, Momoko; Sasaki, Tomoko; Nishi, Kosuke; Tamamoto, Takeshi; Sugahara, Takuya

2018-04-01

Immunoglobulin E (IgE) is involved in the onset of allergic reaction, and the suppression of IgE production leads to alleviation of allergic symptoms. We found that mango peel ethanol extract (MPE) significantly suppresses IgE production by human myeloma cell line U266 cells, suggesting that MPE has an anti-allergic effect by inhibiting the production of IgE. Although mangiferin is contained in mango, which suppresses IgE production by U266 cells, it was not contained in MPE. We investigated the suppressive effect of MPE in 2,4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis model mice. The elevation of serum IgE level was significantly suppressed by oral administration of MPE. Intake of MPE also suppressed the expression level of IL-4 in the DNFB-challenged ears, suggesting that MPE suppresses the IL-4-mediated maturation into IgE-producing cells. Our findings indicate that MPE has a potential to alleviate the increase in serum IgE level that is feature of type I allergy.

IgE antibody on worn highly oxygen-permeable silicone hydrogel contact lenses from patients with contact lens-induced papillary conjunctivitis (CLPC).

PubMed

Zhao, Zhenjun; Fu, Han; Skotnitsky, Cheryl C; Sankaridurg, Padmaja R; Willcox, Mark D P

2008-03-01

To investigate whether the level of IgE is increased in the eyes of patients during general contact lens-induced papillary conjunctivitis (CLPC) events, which involve enlarged papillae across the entire palpebral conjunctiva, or local CLPC events, in which papillae are confined to one or two parts of the area. Worn contact lenses were collected and soaked in phosphate-buffered saline. The levels of eluted IgE and IgE retained on contact lenses were detected by enzyme-linked immunosorbent assay. IgE was detected in 6 of 12 cases of general CLPC, 8 of 21 cases of local CLPC, and none of 14 control contact lenses. The average level of eluted IgE was 0.54 +/- 1.06 IU/contact lens, 0.28 +/- 0.54 IU/contact lens, and 0.04 +/- 0.06 IU/contact lens for general CLPC, local CLPC, and the control group, respectively. The incidences of positive IgE were significantly higher in patients with CLPC (general and local) than in control subjects, but no statistical difference was found between general and local CLPC. Generally higher amounts of retained IgE were detected on contact lenses that had increased levels of eluted IgE. Contact lenses that were collected before or after a CLPC event did not show increased levels of IgE. The level of IgE is increased in the eyes of some patients during an acute event of CLPC. The similar incidence of IgE-positive cases and levels of IgE from general and local CLPC contact lenses suggest that the conditions may share similar causal pathways.

Sex-dependent effects of ultraviolet radiation on the marine amphipod Ampithoe valida (Ampithoidae).

PubMed

Valiñas, Macarena S; Helbling, E Walter

2015-06-01

The combined effects of solar radiation and diet on the marine amphipod Ampithoe valida were investigated exposing individuals to two solar radiation treatments: PAB (>280 nm, PAR+UV-A+UV-B) and P (>400 nm, only PAR), and three diets: poor (Ulva rigida) and rich (Porphyra columbina) in UV-absorbing compounds (UVAC), and mixed diet: (U. rigida+P. columbina). Females of A. valida showed higher food consumption rates when diets contained P. columbina, and preferred this macroalgae rather than U. rigida, resulting in a higher content of UVAC in their bodies. Moreover, the content of UVAC increased in the PAB treatment, thus suggesting the existence of a mechanism to accumulate these compounds under UVR. Although UVR affected the survival, the highest mortality rates were found in those females fed with poor-UVAC diets, which evidence that UVAC provided partial protection against UVR. Males preferred mixed diet, and did not show preference for any particular macroalgae. No differences in mortality were observed between radiation treatments, indicating that UVR did not affect the survival of males, independently if they accumulated UVAC or not. The vulnerability of females to UVR would be partially determined by the type of food consumed, which in turn would be closely related to the macroalgae composition of the intertidal they inhabiting. These effects could be even more pronounced under a global change scenario. Copyright © 2015 Elsevier B.V. All rights reserved.

The amyloid fold of Gad m 1 epitopes governs IgE binding

PubMed Central

Sánchez, Rosa; Martínez, Javier; Castro, Ana; Pedrosa, María; Quirce, Santiago; Rodríguez-Pérez, Rosa; Gasset, María

2016-01-01

Amyloids are polymeric structural states formed from locally or totally unfolded protein chains that permit surface reorganizations, stability enhancements and interaction properties that are absent in the precursor monomers. β-Parvalbumin, the major allergen in fish allergy, forms amyloids that are recognized by IgE in the patient sera, suggesting a yet unknown pathological role for these assemblies. We used Gad m 1 as the fish β-parvalbumin model and a combination of approaches, including peptide arrays, recombinant wt and mutant chains, biophysical characterizations, protease digestions, mass spectrometry, dot-blot and ELISA assays to gain insights into the role of amyloids in the IgE interaction. We found that Gad m 1 immunoreactive regions behave as sequence-dependent conformational epitopes that provide a 1000-fold increase in affinity and the structural repetitiveness required for optimal IgE binding and cross-linking upon folding into amyloids. These findings support the amyloid state as a key entity in type I food allergy. PMID:27597317

Macrophage triggering by aggregated immunoglobulins. II. Comparison of IgE and IgG aggregates or immune complexes.

PubMed Central

Pestel, J; Dessaint, J P; Joseph, M; Bazin, H; Capron, A

1984-01-01

Macrophages incubated with complexed or aggregated IgE released beta-glucuronidase (beta-G) within 30 min. In contrast in the presence of aggregated or complexed IgG, macrophages liberated equivalent amount of beta-G only after 6 h incubation. In addition the rapid macrophage stimulation induced by aggregated IgE was also followed by a faster 3H-glucosamine incorporation when compared to the delayed activation caused by aggregated IgG. However, macrophages stimulated either by IgG or by IgE oligomers produced the same percentage of plasminogen activator at 24 h. In contrast, while the interaction between macrophages and aggregated IgE was only followed by a peak of cyclic GMP and a beta-G release during the first 30 min of incubation, the interaction between macrophages and IgG oligomers was accompanied by a simultaneous increase of cyclic GMP and AMP nucleotides and by an absence of beta-G exocytosis. Moreover, the beta-G release induced by aggregated IgE was increased when macrophages were preincubated with aggregated IgG. This additive effect was not observed in the reverse situation. Finally macrophages activated by IgG oligomers were demonstrated to exert a cytotoxic effect on tumour cells and to kill schistosomula in the presence of a low level of complement. Taken together these results underline the peculiar ability of aggregated or complexed IgE to trigger rapidly the macrophage activation compared to aggregated IgG and can explain the important role of complexed IgE in some macrophage dependent cytotoxicity mechanisms (i.e. in parasitic diseases). PMID:6088135

Cord blood versus age 5 mononuclear cell proliferation on IgE and asthma

PubMed Central

2010-01-01

Background Fetal immune responses following exposure of mothers to allergens during pregnancy may influence the subsequent risk of childhood asthma. However, the association of allergen-induced cord blood mononuclear cell (CBMC) proliferation and cytokine production with later allergic immune responses and asthma has been controversial. Our objective was to compare indoor allergen-induced CBMC with age 5 peripheral blood mononuclear cell (PBMC) proliferation and determine which may be associated with age 5 allergic immune responses and asthma in an inner city cohort. Methods As part of an ongoing cohort study of the Columbia Center for Children's Environmental Health (CCCEH), CBMCs and age 5 PBMCs were cultured with cockroach, mouse, and dust mite protein extracts. CBMC proliferation and cytokine (IL-5 and IFN-γ) responses, and age 5 PBMC proliferation responses, were compared to anti-cockroach, anti-mouse, and anti-dust mite IgE levels, wheeze, cough, eczema and asthma. Results Correlations between CBMC and age 5 PBMC proliferation in response to cockroach, mouse, and dust mite antigens were nonsignificant. Cockroach-, mouse-, and dust mite-induced CBMC proliferation and cytokine responses were not associated with allergen-specific IgE at ages 2, 3, and 5, or with asthma and eczema at age 5. However, after adjusting for potential confounders, age 5 cockroach-induced PBMC proliferation was associated with anti-cockroach IgE, total IgE, and asthma (p < 0.05). Conclusion In contrast to allergen-induced CBMC proliferation, age 5 cockroach-induced PBMC proliferation was associated with age 5 specific and total IgE, and asthma, in an inner-city cohort where cockroach allergens are prevalent and exposure can be high. PMID:20684781

Prevalence and Clinical Relevance of IgE Sensitization to Profilin in Childhood: A Multicenter Study.

PubMed

Asero, Riccardo; Tripodi, Salvatore; Dondi, Arianna; Di Rienzo Businco, Andrea; Sfika, Ifigenia; Bianchi, Annamaria; Candelotti, Paolo; Caffarelli, Carlo; Povesi Dascola, Carlotta; Ricci, Giampaolo; Calamelli, Elisabetta; Maiello, Nunzia; Miraglia Del Giudice, Michele; Frediani, Tullio; Frediani, Simone; Macrì, Francesco; Moretti, Matteo; Dello Iacono, Iride; Patria, Maria Francesca; Varin, Elena; Peroni, Diego; Comberiati, Pasquale; Chini, Loredana; Moschese, Viviana; Lucarelli, Sandra; Bernardini, Roberto; Pingitore, Giuseppe; Pelosi, Umberto; Tosca, Mariangela; Cirisano, Anastasia; Faggian, Diego; Plebani, Mario; Verga, Carmen; Matricardi, Paolo Maria

2015-01-01

Little is known about the prevalence and clinical relevance of hypersensitivity to the plant panallergen profilin in children. The present study aimed to investigate prevalence, risk factors and clinical relevance of profilin sensitization in a large cohort of Italian children of different ages living in different geographic areas. Children with pollen allergy enrolled by 16 pediatric outpatient clinics sited in three main geographic areas of Italy were studied. SPT were carried out with commercial pollen extracts and a commercial purified date palm pollen profilin. IgE specific for allergenic pollen molecules, Phl p 12 (grass profilin) and Pru p 3 (peach lipid transfer protein) were tested by ImmunoCAP FEIA. IgE to Phl p 12 (≥0.35 kU/l) was observed in 296 of the 1,271 participants (23%), including 17 of the 108 (16%) preschool children. Profilin SPT was positive (≥3 mm) in 320/1,271 (25%) participants. The two diagnostic methods were concordant in 1,151 (91%, p < 0.0001) cases. Phl p 12 IgE prevalence declined from northern to southern Italy and was directly associated with IgE to Phl p 1 and/or Phl p 5 and Ole e 1. Among children with IgE to Phl p 12, OAS was provoked by kiwi, melon, watermelon, banana, apricot and cucumber. Profilin sensitization is very frequent among pollen-allergic children, occurs at a very young age and contributes to the development of childhood OAS with a typical pattern of offending foods. Pediatricians should always consider IgE sensitization to profilin while examining pollen-allergic children, even if they are at preschool age. © 2015 S. Karger AG, Basel.

Effect of total lymphoid irradiation on IgE antibody responses in rheumatoid arthritis and systemic lupus erythematosus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Terr, A.I.; Moss, R.B.; Strober, S.

1987-12-01

Thirteen patients with rheumatoid arthritis and four patients with systemic lupus erythematosus and nephritis were treated with total lymphoid irradiation because of severe disease refractory to other forms of treatment. Serum samples before and after irradiation were tested for changes in total serum IgE and for changes in specific IgE antibodies to ryegrass pollen, dust mite, cat dander, and Alternaria. There were no statistically significant changes in total or specific IgE from lymphoid irradiation in these patients. The therapy caused a significant decrease in circulating total lymphocyte and Leu-3 (helper/inducer) T-lymphocyte counts. Therefore, reduction in circulating levels of helper/inducer Tmore » cells does not appear to influence preexisting levels of IgE antibodies.« less

[The role of specific IgE to evolution and prognosis of cow's milk protein allergies in children].

PubMed

Constantinide, Paula; Trandafir, Laura Mihaela; Burlea, M

2011-01-01

Cow's milk allergy affects 8% of infants less than 1 year of age. The allergy is usually transient, with most children tolerating ingested cow'milk by age 3 years. This prospective study analyzes the clinical course, development of tolerance and risk for other atopy (asthma, rhinoconjunctivitis, atopic dermatitis) in children with cow's milk allergy. We followed 71 infants hospitalized between January 2006 - January 2010 in two clinic of Pediatrics from Iaşi and Galaţi with gastro-intestinal, respiratory and skin signs and symptoms of cow's milk allergy. In this study were identified atopic symptoms and diseases, family history of atopy, measured serum total IgE levels and was evaluated development of tolerance to cow's milk. IgE levels was measured at diagnosis, 12 months after diagnosis and recovery tolerance to cow's milk. Patients were followed to acquire tolerance to cow milk. The median age of the patients was 7.57 months +/- 2.73DS. IgE-mediated cow's milk allergy was detected in 40.85% (29 cases) of children at diagnosis. After 12 months of follow 7 (24.14%) of 29 cases initially IgE positive became negative. The first rechallenge was carried out 12 months after diagnosis at mean age 1.6 years (95%CI, 1.5-1.6 years) and the result was positive in 12 cases of IgE negative group. All children (100% of cases) with IgE-negative cow'milk allergy were tolerant by 3.0 years old (P < 0.0001) compared to 70.73% in children with positive IgE. In the end 17.24% of patiens with IgE-mediated cow milk allergy presented respiratory and skin atopic sings. Are there significant differences about the persistent cow'milk allergy between the group of children with positive IgE compared to negative IgE. (p = 0.1918, 95% CI). Most children recover their tolerance to cow milk during childhood and those with negative IgE even at young ages. Patients with positive IgE have an increased risk for allergic diseases, food and inhaled allergens sensitization and development of

Chimeras of Bet v 1 and Api g 1 reveal heterogeneous IgE responses in patients with birch pollen allergy

PubMed Central

Gepp, Barbara; Lengger, Nina; Bublin, Merima; Hemmer, Wolfgang; Breiteneder, Heimo; Radauer, Christian

2014-01-01

Background Characterization of IgE-binding epitopes of allergens and determination of their patient-specific relevance is crucial for the diagnosis and treatment of allergy. Objective We sought to assess the contribution of specific surface areas of the major birch pollen allergen Bet v 1.0101 to binding IgE of individual patients. Methods Four distinct areas of Bet v 1 representing in total 81% of its surface were grafted onto the scaffold of its homolog, Api g 1.0101, to yield the chimeras Api-Bet-1 to Api-Bet-4. The chimeras were expressed in Escherichia coli and purified. IgE binding of 64 sera from Bet v 1–sensitized subjects with birch pollen allergy was determined by using direct ELISA. Specificity was assessed by means of inhibition ELISA. Results rApi g 1.0101, Api-Bet-1, Api-Bet-2, Api-Bet-3, and Api-Bet-4 bound IgE from 44%, 89%, 80%, 78%, and 48% of the patients, respectively. By comparing the amount of IgE binding to the chimeras and to rApi g 1.0101, 81%, 70%, 75%, and 45% of the patients showed significantly enhanced IgE binding to Api-Bet-1, Api-Bet-2, Api-Bet-3, and Api-Bet-4, respectively. The minority (8%) of the sera revealed enhanced IgE binding exclusively to a single chimera, whereas 31% showed increased IgE binding to all 4 chimeras compared with rApi g 1.0101. The chimeras inhibited up to 70% of IgE binding to rBet v 1.0101, confirming the specific IgE recognition of the grafted regions. Conclusion The Bet v 1–specific IgE response is polyclonal, and epitopes are spread across the entire Bet v 1 surface. Furthermore, the IgE recognition profile of Bet v 1 is highly patient specific. PMID:24529686

Chimeras of Bet v 1 and Api g 1 reveal heterogeneous IgE responses in patients with birch pollen allergy.

PubMed

Gepp, Barbara; Lengger, Nina; Bublin, Merima; Hemmer, Wolfgang; Breiteneder, Heimo; Radauer, Christian

2014-07-01

Characterization of IgE-binding epitopes of allergens and determination of their patient-specific relevance is crucial for the diagnosis and treatment of allergy. We sought to assess the contribution of specific surface areas of the major birch pollen allergen Bet v 1.0101 to binding IgE of individual patients. Four distinct areas of Bet v 1 representing in total 81% of its surface were grafted onto the scaffold of its homolog, Api g 1.0101, to yield the chimeras Api-Bet-1 to Api-Bet-4. The chimeras were expressed in Escherichia coli and purified. IgE binding of 64 sera from Bet v 1-sensitized subjects with birch pollen allergy was determined by using direct ELISA. Specificity was assessed by means of inhibition ELISA. rApi g 1.0101, Api-Bet-1, Api-Bet-2, Api-Bet-3, and Api-Bet-4 bound IgE from 44%, 89%, 80%, 78%, and 48% of the patients, respectively. By comparing the amount of IgE binding to the chimeras and to rApi g 1.0101, 81%, 70%, 75%, and 45% of the patients showed significantly enhanced IgE binding to Api-Bet-1, Api-Bet-2, Api-Bet-3, and Api-Bet-4, respectively. The minority (8%) of the sera revealed enhanced IgE binding exclusively to a single chimera, whereas 31% showed increased IgE binding to all 4 chimeras compared with rApi g 1.0101. The chimeras inhibited up to 70% of IgE binding to rBet v 1.0101, confirming the specific IgE recognition of the grafted regions. The Bet v 1-specific IgE response is polyclonal, and epitopes are spread across the entire Bet v 1 surface. Furthermore, the IgE recognition profile of Bet v 1 is highly patient specific. Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.

Allergy-related outcomes in relation to serum IgE: results from the National Health and Nutrition Examination Survey 2005-2006.

PubMed

Salo, Päivi M; Calatroni, Agustin; Gergen, Peter J; Hoppin, Jane A; Sever, Michelle L; Jaramillo, Renee; Arbes, Samuel J; Zeldin, Darryl C

2011-05-01

The National Health and Nutrition Examination Survey (NHANES) 2005-2006 was the first population-based study to investigate levels of serum total and allergen-specific IgE in the general US population. We estimated the prevalence of allergy-related outcomes and examined relationships between serum IgE levels and these outcomes in a representative sample of the US population. Data for this cross-sectional analysis were obtained from NHANES 2005-2006. Study subjects aged 6 years and older (n = 8086) had blood taken for measurement of total IgE and 19 specific IgE levels against common aeroallergens, including Alternaria alternata, Aspergillus fumigatus, Bermuda grass, birch, oak, ragweed, Russian thistle, rye grass, cat dander, cockroach, dog dander, dust mite (Dermatophagoides farinae and Dermatophagoides pteronyssinus), mouse and rat urine proteins, and selected foods (egg white, cow's milk, peanut, and shrimp). Serum samples were analyzed for total and allergen-specific IgE by using the Pharmacia CAP System. Information on allergy-related outcomes and demographics was collected by questionnaire. In NHANES 2005-2006, 6.6% reported current hay fever, and 23.5% had current allergies. Allergy-related outcomes increased with increasing total IgE levels (adjusted odds ratios for a 10-fold increase in total IgE level of 1.86 [95% CI, 1.44-2.41] for hay fever and 1.64 [95% CI, 1.41-1.91] for allergies). Increased levels of plant-, pet-, and mold-specific IgE contributed independently to allergy-related symptoms. The greatest increase in odds was observed for hay fever and plant-specific IgE (adjusted odds ratio, 4.75; 95% CI, 3.83-5.88). In the US population self-reported allergy symptoms are most consistently associated with increased levels of plant-, pet-, and mold-specific IgE. Published by Mosby, Inc.

Clinical evaluation of total IgE in tears of patients with allergic conjunctivitis disease using a novel application of the immunochromatography method.

PubMed

Inada, Noriko; Shoji, Jun; Kato, Hiroshi; Kiely, Surayah; Mulyanto; Sawa, Mitsuru

2009-12-01

The determination of total IgE in tears is useful as a diagnostic tool in allergic conjunctivitis disease (ACD). We evaluated the efficacy of this diagnostic tool for ACD, which is a clinically applicable novel immunochromagraphic method to determine total IgE in tears. The subjects comprised 4 groups: 15 patients with vernal keratoconjunctivitis (VKC group), 8 patients with atopic keratoconjunctivitis (AKC group), 18 patients with allergic conjunctivitis (AC group), and 7 normal healthy volunteers as a control (control group). Tears were sampled using filter paper, and the total IgE in tears was determined by immunochromatography assay. Semiquantitative determination was carried out by examining the intensity of the colored line using an immunochromatoreader (IgE index). The relationship between IgE indices in tears and total IgE levels in serum or between IgE indices and the clinical scores of ACD was examined. The positive ratio obtained by this novel application of the immunochromatography assay was 38 of the 41 in the patients with ACD and none in the 7 controls. IgE indices for the VKC group, AKC group and AC group were 27.5 +/- 15.6, 19.8 +/- 15.8, and 4.0 +/- 3.1 (mean +/- SD), respectively. IgE indices in tears showed significant correlation with both total IgE levels in serum (P < 0.001, r = 0.76) and clinical scores of ACD (P < 0.001, r = 0.57). The novel application of the immunochromatography assay to assess the total IgE in tears is a useful clinical tool to investigate ACD.

An assay that may predict the development of IgG enhancing allergen-specific IgE binding during birch immunotherapy

PubMed Central

Selb, R.; Eckl-Dorna, J.; Vrtala, S.; Valenta, R.; Niederberger, V.

2017-01-01

Background It has been shown that birch pollen immunotherapy can induce IgG antibodies which enhance IgE binding to Bet v 1. We aimed to develop a serological assay to predict the development of antibodies which enhance IgE binding to Bet v 1 during immunotherapy. Methods In 18 patients treated by Bet v 1-fragment-specific immunotherapy, the effects of IgG antibodies specific for the fragments on the binding of IgE antibodies to Bet v 1 were measured by ELISA. Blocking and possible enhancing effects on IgE binding were compared with skin sensitivity to Bet v 1 after treatment. Results We found that fragment-specific IgG enhanced IgE binding to Bet v 1 in two patients who also showed an increase of skin sensitivity to Bet v 1. Conclusion Our results indicate that it may be possible to develop serological tests which predict the induction of unfavourable IgG antibodies enhancing the binding of IgE to Bet v 1 during immunotherapy. PMID:23998344

Comprehensive 3D-modeling of allergenic proteins and amino acid composition of potential conformational IgE epitopes

PubMed Central

Oezguen, Numan; Zhou, Bin; Negi, Surendra S.; Ivanciuc, Ovidiu; Schein, Catherine H.; Labesse, Gilles; Braun, Werner

2008-01-01

Similarities in sequences and 3D structures of allergenic proteins provide vital clues to identify clinically relevant IgE cross-reactivities. However, experimental 3D structures are available in the Protein Data Bank for only 5% (45/829) of all allergens catalogued in the Structural Database of Allergenic Proteins (SDAP, http://fermi.utmb.edu/SDAP). Here, an automated procedure was used to prepare 3D-models of all allergens where there was no experimentally determined 3D structure or high identity (95%) to another protein of known 3D structure. After a final selection by quality criteria, 433 reliable 3D models were retained and are available from our SDAP Website. The new 3D models extensively enhance our knowledge of allergen structures. As an example of their use, experimentally derived “continuous IgE epitopes” were mapped on 3 experimentally determined structures and 13 of our 3D-models of allergenic proteins. Large portions of these continuous sequences are not entirely on the surface and therefore cannot interact with IgE or other proteins. Only the surface exposed residues are constituents of “conformational IgE epitopes” which are not in all cases continuous in sequence. The surface exposed parts of the experimental determined continuous IgE epitopes showed a distinct statistical distribution as compared to their presence in typical protein-protein interfaces. The amino acids Ala, Ser, Asn, Gly and particularly Lys have a high propensity to occur in IgE binding sites. The 3D-models will facilitate further analysis of the common properties of IgE binding sites of allergenic proteins. PMID:18621419

Total and allergen-specific IgE levels during and after pregnancy in relation to maternal allergy.

PubMed

Sandberg, Martina; Frykman, Anne; Jonsson, Yvonne; Persson, Marie; Ernerudh, Jan; Berg, Göran; Matthiesen, Leif; Ekerfelt, Christina; Jenmalm, Maria C

2009-07-01

Type 2 T-helper cell (Th2)-skewed immunity is associated with successful pregnancy and the ability to easily direct immune responses to a Th2-polarised profile may be an evolutionary benefit. The Th2-like immunity associated with allergic disease might generate favourable effects for the maintenance of pregnancy, but could also promote development of Th2-like immune responses and allergic disease in the offspring. The aim of this study was to explore, by using IgE as a stable proxy for Th2, the Th1/Th2 balance in allergic and non-allergic women by measuring allergen-specific and total IgE antibody levels in plasma during pregnancy and after delivery. Specific and total IgE antibody levels were determined by ImmunoCAP technology at five occasions during pregnancy (gestational weeks 10-12, 15-16, 25, 35 and 39), as well as at 2 and 12 months after delivery. Thirty-six women without and 20 women with allergic symptoms were included, of whom 13 were sensitised with allergic symptoms and 30 were non-sensitised without allergic symptoms. The levels of total IgE, but not allergen-specific IgE, were increased during early pregnancy when compared to 12 months after delivery in the sensitised women with allergic symptoms, but not in the non-sensitised women without allergic symptoms (p<0.01). This increase in total IgE levels during early pregnancy only in the sensitised women with allergic symptoms indicates that allergy is associated with an enhanced Th2 deviation during pregnancy.

Helminth Allergens, Parasite-Specific IgE, and Its Protective Role in Human Immunity

PubMed Central

Fitzsimmons, Colin Matthew; Falcone, Franco Harald; Dunne, David William

2014-01-01

The Th2 immune response, culminating in eosinophilia and IgE production, is not only characteristic of allergy but also of infection by parasitic worms (helminths). Anti-parasite IgE has been associated with immunity against a range of helminth infections and many believe that IgE and its receptors evolved to help counter metazoan parasites. Allergens (IgE-antigens) are present in only a small minority of protein families and known IgE targets in helminths belong to these same families (e.g., EF-hand proteins, tropomyosin, and PR-1 proteins). During some helminth infection, especially with the well adapted hookworm, the Th2 response is moderated by parasite-expressed molecules. This has been associated with reduced allergy in helminth endemic areas and worm infection or products have been proposed as treatments for allergic conditions. However, some infections (especially Ascaris) are associated with increased allergy and this has been linked to cross-reactivity between worm proteins (e.g., tropomyosins) and highly similar molecules in dust-mites and insects. The overlap between allergy and helminth infection is best illustrated in Anisakis simplex, a nematode that when consumed in under-cooked fish can be both an infective helminth and a food allergen. Nearly 20 molecular allergens have been isolated from this species, including tropomyosin (Ani s 3) and the EF-hand protein, Ani s troponin. In this review, we highlight aspects of the biology and biochemistry of helminths that may have influenced the evolution of the IgE response. We compare dominant IgE-antigens in worms with clinically important environmental allergens and suggest that arrays of such molecules will provide important information on anti-worm immunity as well as allergy. PMID:24592267

Determination of allergen specificity by heavy chains in grass pollen allergen-specific IgE antibodies.

PubMed

Gadermaier, Elisabeth; Flicker, Sabine; Lupinek, Christian; Steinberger, Peter; Valenta, Rudolf

2013-04-01

Affinity and clonality of allergen-specific IgE antibodies are important determinants for the magnitude of IgE-mediated allergic inflammation. We sought to analyze the contribution of heavy and light chains of human allergen-specific IgE antibodies for allergen specificity and to test whether promiscuous pairing of heavy and light chains with different allergen specificity allows binding and might affect affinity. Ten IgE Fabs specific for 3 non-cross-reactive major timothy grass pollen allergens (Phl p 1, Phl p 2, and Phl p 5) obtained by means of combinatorial cloning from patients with grass pollen allergy were used to construct stable recombinant single chain variable fragments (ScFvs) representing the original Fabs and shuffled ScFvs in which heavy chains were recombined with light chains from IgE Fabs with specificity for other allergens by using the pCANTAB 5 E expression system. Possible ancestor genes for the heavy chain and light chain variable region-encoding genes were determined by using sequence comparison with the ImMunoGeneTics database, and their chromosomal locations were determined. Recombinant ScFvs were tested for allergen specificity and epitope recognition by means of direct and sandwich ELISA, and affinity by using surface plasmon resonance experiments. The shuffling experiments demonstrate that promiscuous pairing of heavy and light chains is possible and maintains allergen specificity, which is mainly determined by the heavy chains. ScFvs consisting of different heavy and light chains exhibited different affinities and even epitope specificity for the corresponding allergen. Our results indicate that allergen specificity of allergen-specific IgE is mainly determined by the heavy chains. Different heavy and light chain pairings in allergen-specific IgE antibodies affect affinity and epitope specificity and thus might influence clinical reactivity to allergens. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by

Tracing the Origins of IgE, Mast Cells, and Allergies by Studies of Wild Animals.

PubMed

Hellman, Lars Torkel; Akula, Srinivas; Thorpe, Michael; Fu, Zhirong

2017-01-01

In most industrialized countries, allergies have increased in frequency quite dramatically during the past 50 years. Estimates show that 20-30% of the populations are affected. Allergies have thereby become one of the major medical challenges of the twenty-first century. Despite several theories including the hygiene hypothesis, there are still very few solid clues concerning the causes of this increase. To trace the origins of allergies, we have studied cells and molecules of importance for the development of IgE-mediated allergies, including the repertoire of immunoglobulin genes. These studies have shown that IgE and IgG most likely appeared by a gene duplication of IgY in an early mammal, possibly 220-300 million years ago. Receptors specific for IgE and IgG subsequently appeared in parallel with the increase in Ig isotypes from a subfamily of the recently identified Fc receptor-like molecules. Circulating IgE levels are generally very low in humans and laboratory rodents. However, when dogs and Scandinavian wolfs were analyzed, IgE levels were found to be 100-200 times higher compared to humans, indicating a generally much more active IgE synthesis in free-living animals, most likely connected to intestinal parasite infections. One of the major effector molecules released upon IgE-mediated activation by mast cells are serine proteases. These proteases, which belong to the large family of hematopoietic serine proteases, are extremely abundant and can account for up to 35% of the total cellular protein. Recent studies show that several of these enzymes, including the chymases and tryptases, are old. Ancestors for these enzymes were most likely present in an early mammal more than 200 million years ago before the separation of the three extant mammalian lineages; monotremes, marsupials, and placental mammals. The aim is now to continue these studies of mast cell biology and IgE to obtain additional clues to their evolutionary conserved functions. A focus

Tracing the Origins of IgE, Mast Cells, and Allergies by Studies of Wild Animals

PubMed Central

Hellman, Lars Torkel; Akula, Srinivas; Thorpe, Michael; Fu, Zhirong

2017-01-01

In most industrialized countries, allergies have increased in frequency quite dramatically during the past 50 years. Estimates show that 20–30% of the populations are affected. Allergies have thereby become one of the major medical challenges of the twenty-first century. Despite several theories including the hygiene hypothesis, there are still very few solid clues concerning the causes of this increase. To trace the origins of allergies, we have studied cells and molecules of importance for the development of IgE-mediated allergies, including the repertoire of immunoglobulin genes. These studies have shown that IgE and IgG most likely appeared by a gene duplication of IgY in an early mammal, possibly 220–300 million years ago. Receptors specific for IgE and IgG subsequently appeared in parallel with the increase in Ig isotypes from a subfamily of the recently identified Fc receptor-like molecules. Circulating IgE levels are generally very low in humans and laboratory rodents. However, when dogs and Scandinavian wolfs were analyzed, IgE levels were found to be 100–200 times higher compared to humans, indicating a generally much more active IgE synthesis in free-living animals, most likely connected to intestinal parasite infections. One of the major effector molecules released upon IgE-mediated activation by mast cells are serine proteases. These proteases, which belong to the large family of hematopoietic serine proteases, are extremely abundant and can account for up to 35% of the total cellular protein. Recent studies show that several of these enzymes, including the chymases and tryptases, are old. Ancestors for these enzymes were most likely present in an early mammal more than 200 million years ago before the separation of the three extant mammalian lineages; monotremes, marsupials, and placental mammals. The aim is now to continue these studies of mast cell biology and IgE to obtain additional clues to their evolutionary conserved functions. A focus

Dissociation between skin test reactivity and anti-aeroallergen IgE: Determinants among urban Brazilian children

PubMed Central

Veiga, Rafael V.; Ponte, João C. M.; da Cunha, Sérgio S.; Simões, Silvia M.; Cruz, Álvaro A.; Yazdanbakhsh, Maria; Matos, Sheila M.; Silva, Thiago Magalhães; Figueiredo, Camila A.; Rodrigues, Laura C.; Fiaccone, Rosemeire L.; Cooper, Philip J.; Barreto, Maurício L.

2017-01-01

Background The dissociation between specific IgE and skin prick test reactivity to aeroallergens, a common finding in populations living in low and middle-income countries, has important implications for the diagnosis and treatment of allergic diseases. Few studies have investigated the determinants of this dissociation. In the present study, we explored potential factors explaining this dissociation in children living in an urban area of Northeast Brazil, focusing in particular on factors associated with poor hygiene. Methods Of 1445 children from low income communities, investigated for risk factors of allergies, we studied 481 with specific IgE antibodies to any of Blomia tropicalis, Dermatophagoides pteronyssinus, Periplaneta americana and Blatella germanica allergens. Data on demographic, environmental and social exposures were collected by questionnaire; serum IgG and stool examinations were done to detect current or past infections with viral, bacterial, protozoan and intestinal helminth pathogens. We measured atopy by skin prick testing (SPT) and specific IgE (sIgE) to aerollergens in serum (by ImmunoCAP). SIgE reactivity to B. tropicalis extract depleted of carbohydrates was measured by an in-house ELISA. Total IgE was measured by in house capture ELISA. SNPs were typed using Illumina Omni 2.5. Results Negative skin prick tests in the presence of specific IgE antibodies were frequent. Factors independently associated with a reduced frequency of positive skin prick tests were large number of siblings, the presence of IgG to herpes simplex virus, Ascaris lumbricoides and Trichuris trichiura infections, living in neighborhoods with infrequent garbage collection, presence of rodents and cats in the household and sIgE reactivity to glycosylated B. tropicalis allergens. Also, SNP on IGHE (rs61737468) was negatively associated with SPT reactivity. Conclusions A variety of factors were found to be associated with decreased frequency of SPT such as unhygienic

Dissociation between skin test reactivity and anti-aeroallergen IgE: Determinants among urban Brazilian children.

PubMed

Alcantara-Neves, Neuza M; Veiga, Rafael V; Ponte, João C M; da Cunha, Sérgio S; Simões, Silvia M; Cruz, Álvaro A; Yazdanbakhsh, Maria; Matos, Sheila M; Silva, Thiago Magalhães; Figueiredo, Camila A; Pontes-de-Carvalho, Lain C; Rodrigues, Laura C; Fiaccone, Rosemeire L; Cooper, Philip J; Barreto, Maurício L

2017-01-01

The dissociation between specific IgE and skin prick test reactivity to aeroallergens, a common finding in populations living in low and middle-income countries, has important implications for the diagnosis and treatment of allergic diseases. Few studies have investigated the determinants of this dissociation. In the present study, we explored potential factors explaining this dissociation in children living in an urban area of Northeast Brazil, focusing in particular on factors associated with poor hygiene. Of 1445 children from low income communities, investigated for risk factors of allergies, we studied 481 with specific IgE antibodies to any of Blomia tropicalis, Dermatophagoides pteronyssinus, Periplaneta americana and Blatella germanica allergens. Data on demographic, environmental and social exposures were collected by questionnaire; serum IgG and stool examinations were done to detect current or past infections with viral, bacterial, protozoan and intestinal helminth pathogens. We measured atopy by skin prick testing (SPT) and specific IgE (sIgE) to aerollergens in serum (by ImmunoCAP). SIgE reactivity to B. tropicalis extract depleted of carbohydrates was measured by an in-house ELISA. Total IgE was measured by in house capture ELISA. SNPs were typed using Illumina Omni 2.5. Negative skin prick tests in the presence of specific IgE antibodies were frequent. Factors independently associated with a reduced frequency of positive skin prick tests were large number of siblings, the presence of IgG to herpes simplex virus, Ascaris lumbricoides and Trichuris trichiura infections, living in neighborhoods with infrequent garbage collection, presence of rodents and cats in the household and sIgE reactivity to glycosylated B. tropicalis allergens. Also, SNP on IGHE (rs61737468) was negatively associated with SPT reactivity. A variety of factors were found to be associated with decreased frequency of SPT such as unhygienic living conditions, infections, total IgE, IgE

Isoforms of the major peanut allergen Ara h 2: IgE binding in children with peanut allergy.

PubMed

Hales, Belinda J; Bosco, Anthony; Mills, Kristina L; Hazell, Lee A; Loh, Richard; Holt, Patrick G; Thomas, Wayne R

2004-10-01

The major peanut allergen Ara h 2 consists of two isoforms, namely Ara h 2.0101 and Ara h 2.0201. The recently identified Ara h 2.0201 isoform contains an extra 12 amino acids including an extra copy of the reported immunodominant epitope DPYSPS. This study aimed to evaluate the IgE binding of the two Ara h 2 isoforms. Ten clones of Ara h 2 were sequenced to assess the relative frequency of the Ara h 2 isoforms and to identify whether there was further variation in the Ara h 2 sequence. IgE binding to Ara h 2.0101 and Ara h 2.0201 was measured for 70 peanut-allergic children using an IgE DELFIA assay to quantitate specific IgE binding. A competition assay was used to measure whether Ara h 2.0201 contained IgE epitopes other than those found for Ara h 2.0101. The original Ara h 2.0101 sequence was found for 6/10 clones and Ara h 2.0201 was found for 2/10 clones. Ara h 2.0201 had the expected insertion of 12 amino acids as well as substitutions at positions 40 (40G) and 142 (142E). Two new isoforms were identified as different polymorphisms of position 142. One Ara h 2.01 clone (Ara h 2.0102) contained 142E and one Ara h 2.02 clone (Ara h 2.0202) contained 142D. A polymorphism that was previously identified by other investigators at position 77 (77Q or 77R) was not found for any of the 10 sequences. Although the level of IgE binding to Ara h 2.0201 of individual patients was frequently higher than the binding to Ara h 2.0101 (p < 0.01), there was a strong correlation in binding to both isoforms (r = 0.987, p < 0.0001) and when analyzed as a group the means were similar. Ara h 2.0101 was not as efficient at blocking reactivity to Ara h 2.0201 indicating there is an additional IgE specificity for the Ara h 2.0201 isoform. Ara h 2.0201 has similar but higher IgE binding than the originally sequenced Ara h 2.0101 isoform and contains other IgE specificities.

Allergy-related outcomes in relation to serum IgE: Results from the National Health and Nutrition Examination Survey 2005–2006

PubMed Central

Salo, Päivi M.; Calatroni, Agustin; Gergen, Peter J.; Hoppin, Jane A.; Sever, Michelle L.; Jaramillo, Renee; Arbes, Samuel J.; Zeldin, Darryl C.

2011-01-01

Background The National Health and Nutrition Examination Survey (NHANES) 2005–2006 was the first population-based study to investigate levels of serum total and allergen-specific immunoglobulin E (IgE) in the general US population. Objective We estimated prevalence of allergy-related outcomes and examined relationships between serum IgE levels and these outcomes in a representative sample of the US population. Methods Data for this cross-sectional analysis were obtained from the NHANES 2005–2006. Study subjects aged 6 years and older (N=8086) had blood taken for measurement of total IgE and 19 specific IgEs against common aeroallergens, including Alternaria alternata, Aspergillus fumigatus, Bermuda grass, birch, oak, ragweed, Russian thistle, rye grass, cat dander, cockroach, dog dander, dust mite (Dermatophagoides farinae and D. pteronyssinus), mouse and rat urine proteins; and selected foods (egg white, cow’s milk, peanut, and shrimp). Serum samples were analyzed for total and allergen-specific IgEs using the Pharmacia CAP System. Information on allergy-related outcomes and demographics was collected by questionnaire. Results In the NHANES 2005–2006, 6.6% reported current hay fever and 23.5% suffered from current allergies. Allergy-related outcomes increased with increasing total IgE (adjusted ORs for a 10-fold increase in total IgE =1.86, 95% CI:1.44–2.41 for hay fever and 1.64, 95% CI: 1.41–1.91 for allergies). Elevated levels of plant-, pet-, and mold-specific IgEs contributed independently to allergy-related symptoms. The greatest increase in odds was observed for hay fever and plant-specific IgEs (adjusted OR=4.75, 95% CI:3.83–5.88). Conclusion In the US population, self-reported allergy symptoms are most consistently associated with elevated levels of plant-, pet-, and mold-specific IgEs. PMID:21320720

New strategies for allergen T cell epitope identification: going beyond IgE

PubMed Central

Schulten, Véronique; Peters, Bjoern; Sette, Alessandro

2014-01-01

Background Type I allergy and allergic asthma are common diseases in the developed world associated with IgE antibodies and Th2 cell reactivity. To date, the only causative treatment for allergic disease is specific immunotherapy (SIT). Method Here, we review recent works from our laboratory focused on identifying human T cell epitopes associated with allergic disease and their potential use as biomarkers or therapeutic targets for SIT. In previous studies, we have mapped T cell epitopes associated with the major ten Timothy grass (Tg) allergens, defined on the basis of human IgE reactivity by ELISPOT. Results Interestingly, in about 33% of allergic donors no T cell epitopes from overlapping peptides spanning the entire sequences of these allergens were identified, despite vigorous T cell responses to the Tg extract. Using a bioinformatics-proteomic approach, we identified a set of 93 novel Tg proteins, many of which were found to elicit IL-5 production in T cells from allergic donors despite lacking IgE reactivity. Next, we assessed T cell responses to the novel Tg proteins in donors who had been treated with subcutaneous specific immunotherapy (SCIT). A subset of these proteins showed a strong reduction of IL-5 responses in donors who had received SCIT compared to allergic donors, which correlated with patient's self-reported improvement of allergic symptoms. Conclusion A bioinformatics-proteomic approach has successfully identified additional Tg-derived T cell targets independent of IgE reactivity. This method can be applied to other allergies potentially leading to the discovery of promising therapeutic targets for allergen-specific immunotherapy. PMID:25402674

Intrinsic transcriptional heterogeneity in B cells controls early class switching to IgE

PubMed Central

Wu, Yee Ling; Teichmann, Sarah A.

2017-01-01

Noncoding transcripts originating upstream of the immunoglobulin constant region (I transcripts) are required to direct activation-induced deaminase to initiate class switching in B cells. Differential regulation of Iε and Iγ1 transcription in response to interleukin 4 (IL-4), hence class switching to IgE and IgG1, is not fully understood. In this study, we combine novel mouse reporters and single-cell RNA sequencing to reveal the heterogeneity in IL-4–induced I transcription. We identify an early population of cells expressing Iε but not Iγ1 and demonstrate that early Iε transcription leads to switching to IgE and occurs at lower activation levels than Iγ1. Our results reveal how probabilistic transcription with a lower activation threshold for Iε directs the early choice of IgE versus IgG1, a key physiological response against parasitic infestations and a mediator of allergy and asthma. PMID:27994069

Immunization with Hypoallergens of Shrimp Allergen Tropomyosin Inhibits Shrimp Tropomyosin Specific IgE Reactivity

PubMed Central

Wai, Christine Y. Y.; Leung, Nicki Y. H.; Ho, Marco H. K.; Gershwin, Laurel J.; Shu, Shang An; Leung, Patrick S. C.; Chu, Ka Hou

2014-01-01

Designer proteins deprived of its IgE-binding reactivity are being sought as a regimen for allergen-specific immunotherapy. Although shrimp tropomyosin (Met e 1) has long been identified as the major shellfish allergen, no immunotherapy is currently available. In this study, we aim at identifying the Met e 1 IgE epitopes for construction of hypoallergens and to determine the IgE inhibitory capacity of the hypoallergens. IgE-binding epitopes were defined by three online computational models, ELISA and dot-blot using sera from shrimp allergy patients. Based on the epitope data, two hypoallergenic derivatives were constructed by site-directed mutagenesis (MEM49) and epitope deletion (MED171). Nine regions on Met e 1 were defined as the major IgE-binding epitopes. Both hypoallergens MEM49 and MED171 showed marked reduction in their in vitro reactivity towards IgE from shrimp allergy patients and Met e 1-sensitized mice, as well as considerable decrease in induction of mast cell degranulation as demonstrated in passive cutaneous anaphylaxis assay. Both hypoallergens were able to induce Met e 1-recognizing IgG antibodies in mice, specifically IgG2a antibodies, that strongly inhibited IgE from shrimp allergy subjects and Met e 1-sensitized mice from binding to Met e 1. These results indicate that the two designer hypoallergenic molecules MEM49 and MED171 exhibit desirable preclinical characteristics, including marked reduction in IgE reactivity and allergenicity, as well as ability to induce blocking IgG antibodies. This approach therefore offers promises for development of immunotherapeutic regimen for shrimp tropomyosin allergy. PMID:25365343

Immunization with Hypoallergens of shrimp allergen tropomyosin inhibits shrimp tropomyosin specific IgE reactivity.

PubMed

Wai, Christine Y Y; Leung, Nicki Y H; Ho, Marco H K; Gershwin, Laurel J; Shu, Shang An; Leung, Patrick S C; Chu, Ka Hou

2014-01-01

Designer proteins deprived of its IgE-binding reactivity are being sought as a regimen for allergen-specific immunotherapy. Although shrimp tropomyosin (Met e 1) has long been identified as the major shellfish allergen, no immunotherapy is currently available. In this study, we aim at identifying the Met e 1 IgE epitopes for construction of hypoallergens and to determine the IgE inhibitory capacity of the hypoallergens. IgE-binding epitopes were defined by three online computational models, ELISA and dot-blot using sera from shrimp allergy patients. Based on the epitope data, two hypoallergenic derivatives were constructed by site-directed mutagenesis (MEM49) and epitope deletion (MED171). Nine regions on Met e 1 were defined as the major IgE-binding epitopes. Both hypoallergens MEM49 and MED171 showed marked reduction in their in vitro reactivity towards IgE from shrimp allergy patients and Met e 1-sensitized mice, as well as considerable decrease in induction of mast cell degranulation as demonstrated in passive cutaneous anaphylaxis assay. Both hypoallergens were able to induce Met e 1-recognizing IgG antibodies in mice, specifically IgG2a antibodies, that strongly inhibited IgE from shrimp allergy subjects and Met e 1-sensitized mice from binding to Met e 1. These results indicate that the two designer hypoallergenic molecules MEM49 and MED171 exhibit desirable preclinical characteristics, including marked reduction in IgE reactivity and allergenicity, as well as ability to induce blocking IgG antibodies. This approach therefore offers promises for development of immunotherapeutic regimen for shrimp tropomyosin allergy.

Chinese herbal extracts of Rubia cordifolia and Dianthus superbus suppress IgE production and prevent peanut-induced anaphylaxis

PubMed Central

2011-01-01

Background Peanut allergy is characterized by increased levels of peanut-specific IgE in the serum of most patients. Thus, the most logical therapy would be to inhibit the IgE production by committed B-cells. This study aims to investigate the unreported anti-IgE effects of Chinese herbal extracts of Rubia cordifolia (Qiancao) and Dianthus superbus (Qumai). Methods Seventy herbal extracts were tested for their ability to reduce IgE secretion by a human B-cell line. Those with the lowest inhibitory concentration 50 (IC50) values were tested in a mouse model of peanut-anaphylaxis. Anaphylactic scores, body temperature, plasma histamine and peanut-specific-immunoglobulins were determined. Results Rubia cordifolia and Dianthus superbus inhibited the in vitro IgE production by a human B-cell line in a dose-dependent manner and the in vivo IgE production in a murine model of peanut allergy without affecting peanut-specific-IgG1 levels. After challenge, all mice in the sham groups developed anaphylactic reactions and increased plasma histamine levels. The extract-treated mice demonstrated significantly reduced peanut-triggered anaphylactic reactions and plasma histamine levels. Conclusion The extracts of Rubia cordifolia and Dianthus superbus inhibited the IgE production in vivo and in vitro as well as reduced anaphylactic reactions in peanut-allergic mice, suggesting potentials for allergy treatments. PMID:21961957

Characterisation of an engineered trastuzumab IgE antibody and effector cell mechanisms targeting HER2/neu-positive tumour cells

PubMed Central

2010-01-01

Trastuzumab (Herceptin®), a humanized IgG1 antibody raised against the human epidermal growth factor receptor 2 (HER2/neu), is the main antibody in clinical use against breast cancer. Pre-clinical evidence and clinical studies indicate that trastuzumab employs several anti-tumour mechanisms that most likely contribute to enhanced survival of patients with HER2/neu-positive breast carcinomas. New strategies are aimed at improving antibody-based therapeutics like trastuzumab, e.g. by enhancing antibody-mediated effector function mechanisms. Based on our previous findings that a chimaeric ovarian tumour antigen-specific IgE antibody showed greater efficacy in tumour cell killing, compared to the corresponding IgG1 antibody, we have produced an IgE homologue of trastuzumab. Trastuzumab IgE was engineered with the same light- and heavy-chain variable-regions as trastuzumab, but with an epsilon in place of the gamma-1 heavy-chain constant region. We describe the physical characterisation and ligand binding properties of the trastuzumab IgE and elucidate its potential anti-tumour activities in functional assays. Both trastuzumab and trastuzumab IgE can activate monocytic cells to kill tumour cells, but they operate by different mechanisms: trastuzumab functions in antibody-dependent cell-mediated phagocytosis (ADCP), whereas trastuzumab IgE functions in antibody-dependent cell-mediated cytotoxicity (ADCC). Trastuzumab IgE, incubated with mast cells and HER2/neu-expressing tumour cells, triggers mast cell degranulation, recruiting against cancer cells a potent immune response, characteristic of allergic reactions. Finally, in viability assays both antibodies mediate comparable levels of tumour cell growth arrest. These functional characteristics of trastuzumab IgE, some distinct from those of trastuzumab, indicate its potential to complement or improve upon the existing clinical benefits of trastuzumab. PMID:18941743

[Correlation between positive skin tests to molds, total IgE, and specific IgE using ELISA and mold cultures from the environment of the pediatric allergy patient].

PubMed

García Caballero, R; Nader, O; Morfin Maciel, B

2001-01-01

The aim of this study was to made a correlation between allergic symptoms, positive skin prick test to fungi, total and specific IgE and mold culture in the patient's environmental. There were included 35 children (3-16 years), with skin prick test positive to fungi. The most frequent were: Rhizopus, Aspergillus, Cladosporium and Candida. Total and specific IgE were measured with ELISA, with titers high in 77.2% and 31.4% respectively. Fungal cultures were collected from dwellings and schools. The most frequently isolated mold genera were Cladosporium, Alternaria and Penicillium in the same proportion in both places: dwellings and schools. We concluded fungi are commonly found in children's environment.

Decreased immunoglobulin E (IgE) binding to cashew allergens following sodium sulfite treatment and heating.

PubMed

Mattison, Christopher P; Desormeaux, Wendy A; Wasserman, Richard L; Yoshioka-Tarver, Megumi; Condon, Brian; Grimm, Casey C

2014-07-16

Cashew nut and other nut allergies can result in serious and sometimes life-threatening reactions. Linear and conformational epitopes within food allergens are important for immunoglobulin E (IgE) binding. Methods that disrupt allergen structure can lower IgE binding and lessen the likelihood of food allergy reactions. Previous structural and biochemical data have indicated that 2S albumins from tree nuts and peanuts are potent allergens, and that their structures are sensitive to strong reducing agents such as dithiothreitol. This study demonstrates that the generally regarded as safe (GRAS) compound sodium sulfite effectively disrupted the structure of the cashew 2S albumin, Ana o 3, in a temperature-dependent manner. This study also showed that sulfite is effective at disrupting the disulfide bond within the cashew legumin, Ana o 2. Immunoblotting and ELISA demonstrated that the binding of cashew proteins by rabbit IgG or IgE from cashew-allergic patients was markedly lowered following treatment with sodium sulfite and heating. The results indicate that incorporation of sodium sulfite, or other food grade reagents with similar redox potential, may be useful processing methods to lower or eliminate IgE binding to food allergens.

Prediction of challenge test results by flour-specific IgE and skin prick test in symptomatic bakers.

PubMed

van Kampen, V; Rabstein, S; Sander, I; Merget, R; Brüning, T; Broding, H C; Keller, C; Müsken, H; Overlack, A; Schultze-Werninghaus, G; Walusiak, J; Raulf-Heimsoth, M

2008-07-01

Wheat and rye flours are among the most important allergens causing occupational asthma. Usually, the diagnosis of baker's asthma is based on inhalation challenge tests with flours. To evaluate the relevance of flour-specific serum immunoglobulin E (IgE) and skin prick test (SPT) in the diagnosis of baker's asthma and to define flour-specific IgE concentrations and wheal sizes that allow a prediction of the outcome of challenge testing. Bronchial and nasal challenge tests with wheat (rye) flour were performed in 71 (95) symptomatic bakers. Determinations of flour-specific IgE as well as SPTs were performed in all subjects. Analyses included the calculation of sensitivity, specificity, positive (PPV) and negative predictive values (NPV) at different IgE concentrations and different wheal sizes, and receiver-operating characteristics (ROC) plots with the challenge result as gold standard. Thirty-seven bakers were positive in the challenge with wheat flour, while 63 were positive with rye flour. Depending on the flour-specific IgE concentrations (wheal size), PPV was 74-100% (74-100%) for wheat and 82-100% (91-100%) for rye flour, respectively. The minimal cut-off values with a PPV of 100% were 2.32 kU/l (5.0 mm) for wheat flour and 9.64 kU/l (4.5 mm) for rye flour. The shapes of the ROC plots were similar for wheat and rye flour. High concentrations of flour-specific IgE and clear SPT results in symptomatic bakers are good predictors for a positive challenge test. Challenge tests with flours may be avoided in strongly sensitized bakers.

98 Specific IGE and IGG Binding to Allergoids of Phleum pratense

PubMed Central

Cases, Barbara; Fernandez-Caldas, Enrique; Tudela, Jose Ignacio; Fernandez, Eva Abel; Sanchez-Garcia, Silvia; Ibañez, M. Dolores; Escudero, Carmelo; Casanovas, Miguel

2012-01-01

Background Allergoids were first used in the decades of the 60s and 70s of the last century as an effective treatment of allergic respiratory diseases. Allergoids can be modified with formaldehyde or glutaraldehyde. Modified allergens, or allergoids, decrease the risk of adverse reactions while administering higher allergen doses. The objective of this study was to analyse specific IgE and IgG binding to glutaraldehyde modified and non-modified allergen extracts of Phleum pratense. Methods The sera of 69 patients sensitized to P. pratense were tested. All these patients had signs and symptoms of rhinoconjunctivitis with, or without, asthma in May and June of 2011. All these patients had positive skin prick tests to a standardized extract of P. pratense, and other grass species. Most patients were also sensitized to olive pollen. Specific IgE and IgG binding were analysed by direct ELISA against P. pratense native (non-modified) and allergoid extracts. Relative potencies were evaluated through ELISA inhibition assays, and the protein composition of non-modified and allergoid samples was determined by Mass Spectrometry (MS/MS). Results Mean Specific IgE levels against the native extract was 16.68 ± 11.65 Units (U) and against the allergoid: 7.26 ± 8.24 U (P < 0.0001; Mann-Whitney). On the other hand, mean specific IgG binding against the non-modified extract was 90.34 ± 75.57 U versus 76.19 ± 70.31 U against the allergoid (P = 0.16; Mann-Whitney). Linear regression coefficients obtained between immunoglobulin reactivity against both extracts were: r2 = 0.51 for specific IgE and r2 = 0.83 for specific IgG. An important decrease in the allergenic activity, measured by inhibition ELISA, was clearly observed. The MS/MS assay revealed the presence of the mayor allergen, and some isoforms, in non-modified and allergoid extracts. Conclusions Results obtained demonstrate that the glutaraldehyde polymerization process induces an important decrease in specific IgE binding

IgE Sensitization Profiles Differ between Adult Patients with Severe and Moderate Atopic Dermatitis

PubMed Central

Johansson, Catharina; Lupinek, Christian; Lundeberg, Lena; Crameri, Reto; Valenta, Rudolf; Scheynius, Annika

2016-01-01

Background Atopic dermatitis (AD) is a complex chronic inflammatory disease where allergens can act as specific triggering factors. Aim To characterize the specificities of IgE-reactivity in patients with AD to a broad panel of exogenous allergens including microbial and human antigens. Methodology Adult patients with AD were grouped according to the SCORAD index, into severe (n = 53) and moderate AD (n = 126). As controls 43 patients were included with seborrhoeic eczema and 97 individuals without history of allergy or skin diseases. Specific IgE reactivity was assessed in plasma using Phadiatop®, ImmunoCap™, micro-arrayed allergens, dot-blotted recombinant Malassezia sympodialis allergens, and immune-blotted microbial and human proteins. Results IgE reactivity was detected in 92% of patients with severe and 83% of patients with moderate AD. Sensitization to cat allergens occurred most frequently, followed by sensitization to birch pollen, grass pollen, and to the skin commensal yeast M. sympodialis. Patients with severe AD showed a significantly higher frequency of IgE reactivity to allergens like cat (rFel d 1) and house dust mite (rDer p 4 and 10), to Staphylococcus aureus, M. sympodialis, and to human antigens. In contrast, there were no significant differences in the frequencies of IgE reactivity to the grass pollen allergens rPhl p 1, 2, 5b, and 6 between the two AD groups. Furthermore the IgE reactivity profile of patients with severe AD was more spread towards several different allergen molecules as compared to patients with moderate AD. Conclusion We have revealed a hitherto unknown difference regarding the molecular sensitization profile in patients with severe and moderate AD. Molecular profiling towards allergen components may provide a basis for future investigations aiming to explore the environmental, genetic and epigenetic factors which could be responsible for the different appearance and severity of disease phenotypes in AD. PMID:27228091

IgE Sensitization Profiles Differ between Adult Patients with Severe and Moderate Atopic Dermatitis.

PubMed

Mittermann, Irene; Wikberg, Gustav; Johansson, Catharina; Lupinek, Christian; Lundeberg, Lena; Crameri, Reto; Valenta, Rudolf; Scheynius, Annika

2016-01-01

Atopic dermatitis (AD) is a complex chronic inflammatory disease where allergens can act as specific triggering factors. To characterize the specificities of IgE-reactivity in patients with AD to a broad panel of exogenous allergens including microbial and human antigens. Adult patients with AD were grouped according to the SCORAD index, into severe (n = 53) and moderate AD (n = 126). As controls 43 patients were included with seborrhoeic eczema and 97 individuals without history of allergy or skin diseases. Specific IgE reactivity was assessed in plasma using Phadiatop®, ImmunoCap™, micro-arrayed allergens, dot-blotted recombinant Malassezia sympodialis allergens, and immune-blotted microbial and human proteins. IgE reactivity was detected in 92% of patients with severe and 83% of patients with moderate AD. Sensitization to cat allergens occurred most frequently, followed by sensitization to birch pollen, grass pollen, and to the skin commensal yeast M. sympodialis. Patients with severe AD showed a significantly higher frequency of IgE reactivity to allergens like cat (rFel d 1) and house dust mite (rDer p 4 and 10), to Staphylococcus aureus, M. sympodialis, and to human antigens. In contrast, there were no significant differences in the frequencies of IgE reactivity to the grass pollen allergens rPhl p 1, 2, 5b, and 6 between the two AD groups. Furthermore the IgE reactivity profile of patients with severe AD was more spread towards several different allergen molecules as compared to patients with moderate AD. We have revealed a hitherto unknown difference regarding the molecular sensitization profile in patients with severe and moderate AD. Molecular profiling towards allergen components may provide a basis for future investigations aiming to explore the environmental, genetic and epigenetic factors which could be responsible for the different appearance and severity of disease phenotypes in AD.

Layered Electrical Product Application Protocol (AP). Draft: Initial Graphics Exchange Specification (IGES)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1994-09-01

An application protocol is an information systems engineering view of a specific product. The view represents an agreement on the generic activities needed to design and fabricate the product, the agreement on the information needed to support those activities, and the specific constructs of a product data standard for use in transfering some or all of the information required. This applications protocol describes the data for electrical and electronic products in terms of a product description standard called the Initial Graphics Exchange Specification (IGES). More specifically, the Layered Electrical Product IGES Application Protocol (AP) specifies the mechanisms for defining andmore » exchanging computer-models and their associated data for those products which have been designed in two dimensional geometry so as to be produced as a series of layers in IGES format. The AP defines the appropriateness of the data items for describing the geometry of the various parts of a product (shape and location), the connectivity, and the processing and material characteristics. Excluded is the behavioral requirements which the product was intended to satisfy, except as those requirements have been recorded as design rules or product testing requirements.« less

Time course of total and food specific IgE antibodies (Rast Fx5) in the developing allergic child.

PubMed

Kalach, Nicolas; Soulaines, Pascale; Guerin, Sylvie; de Boissieu, Delphine; Dupont, Christophe

2005-09-01

To analyze the evolution of total and food specific IgE (Rast Fx5) titers in the course of food allergy in children. 925 children, mean age 8.9 + 9.1 years (15 days-18 years), 455 girls and 470 boys, investigated for food allergy in year 1997, underwent serum samples assay for total IgE and of Rast Fx5, Cap System, Pharmacia & Upjohn Diagnostics AB, Uppsala, Sweden, a mix test detecting specific IgE to 6 major food allergens in children, cow's milk proteins (CMP), egg white, peanut, soy, wheat and fish and analyzed as a function of reference values by age. Total IgE titers increased significantly with age, r0.22, p0.0001. The percentage of children with a total IgE level above normal range first increased with age, from 10.3 % at 0-6 months, reaching 38.2 % at 1-2 years and peaking at 56.9% at 4-6 years, then leveled off, 48.1% at 8-12 years (ns vs 4-6 years) and 41.3% above 12 years (ns). Detectable Rast Fx5 increased in a parallel manner until age 4-6 years and then exhibited a progressive decrease from age 6-8 years, differing significantly from total IgE: 31.9% vs 52.9%, p0.01 (6-8 years), 32.2% vs 48.1%, p0.03 (8-12 years), 21.8% vs 41.3%, p0.05 (> 12 years). In these outpatient children investigated for food allergy, the increase with age of the percentage of high total IgE contrasted with the progressive decrease of Rast Fx5 from age 4-6 yr. This biological finding correlates timely with the clinical spontaneous decrease of food allergy in the developing child.

IgE binding to peanut allergens is inhibited by combined D-aspartic and D-glutamic acids

USDA-ARS?s Scientific Manuscript database

D-amino acids (D-aas) are reported to bind to IgE antibodies from people with allergy and asthma. The objectives of this study were to determine if D-aas bind or inhibit IgE binding to peanut allergens, and if they are more effective than L-amino acids (L-aas) in this respect. Several D-aa cocktails...

Intradermal Delivery of Antigens Enhances Specific IgG and Diminishes IgE Production: Potential Use for Vaccination and Allergy Immunotherapy

PubMed Central

Yasuda, Takuwa; Ura, Takehiro; Taniguchi, Masaru; Yoshida, Hisahiro

2016-01-01

Skin is protected by a tough but flexible multilayered barrier and is a front line for immune responses against invading particles. For many years now, skin has been a tissue where certain vaccines are injected for the prevention of infectious disease, however, the detailed mechanisms of the skin immune response are not yet well understood. Using thin and small injection needles, we carefully injected OVA into a restricted region of mouse skin, i.e., intradermal (ID), and examined the antibody response in comparison with subcutaneous (SC) injection or epicutaneous patch administration of OVA. Epicutaneous patches induced a high IgE response against OVA, but IgG production was low. High IgG production was induced by both ID and SC injection, moreover, ID injection induced higher IgG production without any adjutants. Furthermore, OVA-specific IgE production was diminished by ID injection. We found that ID injection could efficiently stimulate skin resident DCs, drive Th1-biased conditions and diminish IgE production. The ID injection response was regulated by Langerin+ dermal DCs, because OVA was taken up mainly by these cells and, after transiently deleting them, the IgE response was no longer diminished and IgG1 production was enhanced. We also tested whether ID injection might be an effective allergy treatment by attempting to inhibit ongoing IgE production in mice with experimentally induced high serum IgE levels. Multiple ID injections of OVA were shown to prevent elevation of serum OVA-specific IgE after repeated allergen challenge. In contrast, SC OVA injection could only transiently inhibit the OVA-specific IgE production. These findings indicated that ID injection results in higher induction of antigen-specific IgG, and thus may be useful for vaccine delivery with little or no adjuvant components. Moreover, the observed diminishment of IgE and induction of Th1-biased immune responses suggest that ID may be a useful injection route for allergy immunotherapy

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

PubMed Central

2011-01-01

Background Two 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). Results Total 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. Conclusion The present results suggest that a low ratio of specific IgE to total IgE levels (in a minority of

Mechanism underlying the suppressor activity of retinoic acid on IL4-induced IgE synthesis and its physiological implication.

PubMed

Seo, Goo-Young; Lee, Jeong-Min; Jang, Young-Saeng; Kang, Seung Goo; Yoon, Sung-Il; Ko, Hyun-Jeong; Lee, Geun-Shik; Park, Seok-Rae; Nagler, Cathryn R; Kim, Pyeung-Hyeun

2017-12-01

The present study extends an earlier report that retinoic acid (RA) down-regulates IgE Ab synthesis in vitro. Here, we show the suppressive activity of RA on IgE production in vivo and its underlying mechanisms. We found that RA down-regulated IgE class switching recombination (CSR) mainly through RA receptor α (RARα). Additionally, RA inhibited histone acetylation of germ-line ε (GL ε) promoter, leading to suppression of IgE CSR. Consistently, serum IgE levels were substantially elevated in vitamin A-deficient (VAD) mice and this was more dramatic in VAD-lecithin:retinol acyltransferase deficient (LRAT -/- ) mice. Further, serum mouse mast cell protease-1 (mMCP-1) level was elevated while frequency of intestinal regulatory T cells (Tregs) were diminished in VAD LRAT -/- mice, reflecting that deprivation of RA leads to allergic immune response. Taken together, our results reveal that RA has an IgE-repressive activity in vivo, which may ameliorate IgE-mediated allergic disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Anti-cetuximab IgE ELISA for identification of patients at a high risk of cetuximab-induced anaphylaxis.

PubMed

Mariotte, Delphine; Dupont, Benoît; Gervais, Radj; Galais, Marie-Pierre; Laroche, Dominique; Tranchant, Aurore; Comby, Elisabeth; Bouhier-Leporrier, Karine; Reimund, Jean-Marie; Le Mauff, Brigitte

2011-01-01

Cetuximab, a chimeric mouse-human IgG1 monoclonal antibody against the epidermal growth factor receptor, has proven effective in the treatment of metastatic colorectal cancer and squamous cell carcinoma of the head and neck. However, a high incidence of immediate hypersensitivity reactions (HSR) to cetuximab after the first infusion has been observed. We have developed a test for identification of patients likely to show treatment-related HSR to cetuximab. An enzyme-linked immunosorbent assay (ELISA) for detecting anti-cetuximab IgEs was developed and tested on serum samples collected from cancer patients before start of cetuximab treatment, and from healthy blood donors. Similar levels of anti-cetuximab IgE were detected in pre-treatment patient sera (24/92, 26.1%) and sera from healthy blood donors (33/117, 28.2%). HSR were observed in 14 out of the 92 patients (15.2%), and 8 of these (57.1%) were grade 3-4. Anti-cetuximab IgEs were detected in 7/8 of the patients (87.5%) with severe HSRs as compared with 14/78 patients (17.9%) with no HSR (p=0.0002). Predictive value of the anti-cetuximab IgE test for HSR events of grades 3-4 was calculated using Receiver Operating Characteristics analysis. With a cut-off value of 29 arbitrary units for the anti-cetuximab IgE, the ELISA test showed a sensitivity of 87.5%, specificity of 82.1%, positive predictive value of 33.3% and negative predictive value of 98.5%. Anti-cetuximab IgE ELISA detection could be a valuable tool to help the physician anticipate an anaphylaxis episode following cetuximab infusion and opt for a suitable alternative treatment.

An optimized assay of specific IgE antibodies to reactive dyes and studies of immunologic responses in exposed workers.

PubMed

Wass, U; Nilsson, R; Nordlinder, R; Belin, L

1990-03-01

Methods of assaying reactive dye-specific IgE antibodies were investigated with a RAST. Sera from three patients, occupationally exposed to a reactive dye, Remazol black B (Chemical Abstract registry number 17095-24-8), were used. Directly dyed disks, that is, disks without any carrier protein, resulted in poor and unreliable measures of specific IgE. In contrast, optimized preparation of conjugates between the dye and human serum albumin resulted in efficient binding of specific IgE. The patients' RAST results were strongly positive, whereas sera from 36 exposed workers but without symptoms and sera from unexposed subjects with high levels of total IgE were negative. The hapten and carrier specificity of the IgE antibodies was studied by direct RAST and RAST inhibition. In one patient, the antibodies were principally hapten specific, whereas another patient was found to have antibodies with a high degree of specificity to the carrier. The third patient's antibodies were intermediate between the other two patients' antibodies in this respect, suggesting that antibody specificity is dependent not only on the nature of the hapten but also on individual immune response factors. The study demonstrates that it is important to use an optimized preparation of dye-protein conjugates to elicit reliable results and a high degree of specific IgE binding in the RAST.

IgE Immune Complexes Stimulate an Increase in Lung Mast Cell Progenitors in a Mouse Model of Allergic Airway Inflammation

PubMed Central

Dahlin, Joakim S.; Ivarsson, Martin A.; Heyman, Birgitta; Hallgren, Jenny

2011-01-01

Mast cell numbers and allergen specific IgE are increased in the lungs of patients with allergic asthma and this can be reproduced in mouse models. The increased number of mast cells is likely due to recruitment of mast cell progenitors that mature in situ. We hypothesized that formation of IgE immune complexes in the lungs of sensitized mice increase the migration of mast cell progenitors to this organ. To study this, a model of allergic airway inflammation where mice were immunized with ovalbumin (OVA) in alum twice followed by three daily intranasal challenges of either OVA coupled to trinitrophenyl (TNP) alone or as immune complexes with IgE-anti-TNP, was used. Mast cell progenitors were quantified by a limiting dilution assay. IgE immune complex challenge of sensitized mice elicited three times more mast cell progenitors per lung than challenge with the same dose of antigen alone. This dose of antigen challenge alone did not increase the levels of mast cell progenitors compared to unchallenged mice. IgE immune complex challenge of sensitized mice also enhanced the frequency of mast cell progenitors per 106 mononuclear cells by 2.1-fold. The enhancement of lung mast cell progenitors by IgE immune complex challenge was lost in FcRγ deficient mice but not in CD23 deficient mice. Our data show that IgE immune complex challenge enhances the number of mast cell progenitors in the lung through activation of an Fc receptor associated with the FcRγ chain. This most likely takes place via activation of FcεRI, although activation via FcγRIV or a combination of the two receptors cannot be excluded. IgE immune complex-mediated enhancement of lung MCp numbers is a new reason to target IgE in therapies against allergic asthma. PMID:21625525

Ara h 1 structure is retained after roasting and is important for enhanced binding to IgE

USDA-ARS?s Scientific Manuscript database

Roasted peanuts bind higher levels of serum IgE than raw peanuts. The contribution of the major allergens to this observation are not well-defined. We compared IgE binding properties of Ara h 1 purified from raw and roasted peanuts, and assess the structural components that may contribute to diffe...

Modulation of the allergen-induced human IgE response in Hu-SCID mice: inhibitory effect of human recombinant IFN-gamma and allergen-derived lipopeptide.

PubMed

Duez, C; Gras-Masse, H; Hammad, H; Akoum, H; Didierlaurent, A; André, C; Tonnel, A B; Pestel, J

2001-01-01

We have previously established a model to study the in vivo human IgE response using humanized SCID mice. Allergic SCID mice were obtained following intraperitoneal injection with mononuclear cells from Dermatophagoides pteronyssinus (Dpt)-sensitive patients, and sensitization by Dpt allergen intraperitoneal injection (immunization) or Dpt aerosol (inhalation). Human serum IgE was measured in allergic SCID mice after administration of human recombinant IFN-gamma or the lipopeptide LP 52-71 (derived from peptide p52-71 from Der p 1, Dpt major allergen, coupled to a lipophilic moiety), during the immunization or the inhalation phase. IFN-gamma inhibited human IgE production when given at the time of immunization, but not during inhalation. This effect was long-lasting as Dpt aerosol, given one month after immunization and IFN-gamma administration, failed to increase IgE levels. Unlike Dpt or p52-71, LP 52-71 failed to induce human IgE production at day 14 and 21 after its injection, but did inhibit the development of the IgE response after a secondary Dpt-challenge. Moreover, LP 52-71 administration 14 days after Dpt inhalation decreased IgE levels, in contrast to peptide 52-71, which increased IgE levels. Thus, taken together these results indicate that the development of the human IgE response in allergic SCID mice can be modulated by modified allergen and a Th1 cytokine.

IGE IN ASTHMATIC HUMAN SERA IS REACTIVE AGAINST MOLD EXTRACTS

EPA Science Inventory

Molds have been associated with various health effects including asthma, but their role in induction of asthma is unclear. However, the presence of mold-specific IgE indicates their capacity to induce allergic responses and possibly exacerbate asthma symptoms. This study was und...

Allergy and parasites: the measurement of total and specific IgE levels in urban and rural communities in Rhodesia.

PubMed

Merrett, T G; Merrett, J; Cookson, J B

1976-03-01

Eighty adult asthmatics living in an African city had a significantly higher serum IgE level (799 u/ml) than the control group (350 u/ml). A high proportion (78.7%) of the asthmatics had demonstrable circulating mite-specific IgE antibodies. The rural population of a filariasis endemic region was investigated and although no allergic subjects were identified, the group had a significantly higher IgE level (1613 u/ml) than the asthmatics and also showed a relatively high incidence of grass pollen-specific IgE antibodies (35%). The discrepancy between clinical history and laboratory results supports the mast cell saturation hypothesis and suggests: (a) an explanation for the susceptibility to allergy of African and Asian immigrants to Great Britain, and (b) a practical approach for preventing allergic reactions in vivo.

IL-4 inhibits the synthesis of IFN-gamma and induces the synthesis of IgE in human mixed lymphocyte cultures.

PubMed

Vercelli, D; Jabara, H H; Lauener, R P; Geha, R S

1990-01-15

The T cell-derived lymphokine IL-4 is essential for the induction of IgE synthesis by human lymphocytes. The IgE-inducing effect of IL-4 is antagonized by IFN-gamma. The secretion of IFN-gamma is vigorously triggered in MLC. Thus, IL-4-stimulated MLC represent a suitable model to characterize the functional antagonism between IL-4 and IFN-gamma. In this report, we show that rIL-4 consistently induced IgE synthesis when added to human primary MLC. IL-4-dependent IgE production required cognate T/B cell recognition, because it was inhibited by antibodies to CD3 and MHC class II (HlA-DR) Ag. A neutralizing anti-IFN-gamma mAb dramatically enhanced IL-4-dependent IgE synthesis by MLC, indicating that endogenous IFN-gamma is a major inhibitor of IgE production. More importantly, addition of rIL-4 markedly inhibited the release of IFN-gamma in supernatants of MLC and Con A-activated PBMC. The decrease in IFN-gamma protein was accompanied by a decreased expression of IFN-gamma mRNA transcripts. The downregulation of IFN-gamma by IL-4 is likely to play an important role in the IL-4-dependent induction of IgE synthesis.

Long Term Persistence of IgE Anti-Varicella Zoster Virus in Pediatric and Adult Serum Post Chicken Pox Infection and after Vaccination with Varicella Virus Vaccine.

PubMed

Smith-Norowitz, Tamar A; Josekutty, Joby; Silverberg, Jonathan I; Lev-Tov, Hadar; Norowitz, Yitzchok M; Kohlhoff, Stephan; Nowakowski, Maja; Durkin, Helen G; Bluth, Martin H

2009-12-01

The production of IgE specific to different viruses (HIV-1, Parvovirus B19, RSV), and the ability for IgE anti-HIV-1 to suppress HIV-1 production in vitro, strongly suggest an important role for IgE and/or anti viral specific IgE in viral pathogenesis. Previous studies in our laboratory were the first to report the presence of IgE anti-varicella zoster virus (VZV) in an adolescent patient with shingles. However, the presence and long term persistence of IgE anti VZV antibodies has not been studied in adults. The presence of serum IgE in addition to IgE and IgG anti-VZV antibody in sera were studied in children (N=12) (0-16 y/o) and adults (N=9) (32-76 y/o) with either a past history of (wild type) chicken pox (N=7 children, 9 adults) or 5 years after vaccination with varicella zoster (N=2 children) (Varicella virus vaccine live, Oka/Merck), as well as in non-infected subjects (N=3 children). Of the patients who had a positive history of chicken pox 13 of 16 (81%) contained IgE anti-VZV antibodies; they were both serum IgEHi (>100 IU/ml) and IgELo (<100 IU/ml). Of the patients who were vaccinated, IgE anti-VZV antibodies were undetected. In contrast, serum from the patients without a history of chicken pox or vaccination did not make either IgE or IgG anti-VZV antibodies. This is the first demonstration of the existence of IgE anti-VZV antibodies, and its long-term persistence in serum of previously infected subjects. Future studies regarding the functional role of anti-viral IgE and its relationship to VZV are warranted.

Rapid polyclonal desensitization with antibodies to IgE and FcεRIα

PubMed Central

Khodoun, Marat V.; Kucuk, Zeynep Yesim; Strait, Richard T.; Krishnamurthy, Durga; Janek, Kevin; Lewkowich, Ian; Morris, Suzanne C.; Finkelman, Fred D.

2013-01-01

Background Rapid desensitization,a procedure in which individuals allergic to an antigen are treated at short intervals with increasing doses of that antigen until they tolerate a large dose, is an effective, but risky way to induce temporary tolerance. Objective To determine whether this approach can be adapted to suppress all IgE-mediated in mice by injecting serially increasing doses of monoclonal antibodies (mAbs) to IgE or FcεRIα. Methods Active and passive models of antigen- and anti-IgE mAb-induced IgE-mediated anaphylaxis were used. Mice were desensitized with serially increasing doses of anti-IgE mAb, anti-FcεRIα mAb or antigen. Development of shock (hypothermia), histamine and mast cell protease release, cytokine secretion, calcium flux and changes in cell number and FcεRI and IgE expression were evaluated. Results Rapid desensitization with anti-IgE mAb suppressed IgE-mediated immediate hypersensitivity; however, some mice developed mild anaphylaxis during desensitization. Rapid desensitization with anti-FcεRIα mAb that only binds FcεRI that is not occupied by IgE suppressed both active and passive IgE-mediated anaphylaxis without inducing disease. It quickly, but temporarily, suppressed IgE-mediated anaphylaxis by decreasing mast cell signaling through FcεRI, then slowly slowlyinduced longer lasting mast cell unresponsiveness by removing membrane FcεRI. Rapid desensitization with anti-FcεRIα mAb was safer and longer-lasting than rapid desensitization with antigen. Conclusion A rapid desensitization approach with anti-FcεRIα mAb safely desensitizes mice to IgE-mediated anaphylaxis by inducing mast cell anergy and later, removing all mast cell IgE. Rapid desensitization with an anti-human FcεRIα mAb may be able to prevent human IgE-mediated anaphylaxis. PMID:23632296

Recombinant allergen-based IgE testing to distinguish bee and wasp allergy.

PubMed

Mittermann, Irene; Zidarn, Mihaela; Silar, Mira; Markovic-Housley, Zora; Aberer, Werner; Korosec, Peter; Kosnik, Mitja; Valenta, Rudolf

2010-06-01

The identification of the disease-causing insect in venom allergy is often difficult. To establish recombinant allergen-based IgE tests to diagnose bee and yellow jacket wasp allergy. Sera from patients with bee and/or wasp allergy (n = 43) and patients with pollen allergy with false-positive IgE serology to venom extracts were tested for IgE reactivity in allergen extract-based tests or with purified allergens, including nonglycosylated Escherichia coli-expressed recombinant (r) Api m 1, rApi m 2, rVes v 5, and insect cell-expressed, glycosylated rApi m 2 as well as 2 natural plant glycoproteins (Phl p 4, bromelain). The patients with venom allergy could be diagnosed with a combination of E coli-expressed rApi m 1, rApi m 2, and rVes v 5 whereas patients with pollen allergy remained negative. For a group of 29 patients for whom the sensitizing venom could not be identified with natural allergen extracts, testing with nonglycosylated allergens allowed identification of the sensitizing venom. Recombinant nonglycosylated allergens also allowed definition of the sensitizing venom for those 14 patients who had reacted either with bee or wasp venom extracts. By IgE inhibition studies, it is shown that glycosylated Api m 2 contains carbohydrate epitopes that cross-react with natural Api m 1, Ves v 2, natural Phl p 4, and bromelain, thus identifying cross-reactive structures responsible for serologic false-positive test results or double-positivity to bee and wasp extracts. Nonglycosylated recombinant bee and wasp venom allergens allow the identification of patients with bee and wasp allergy and should facilitate accurate prescription of venom immunotherapy. Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Staphylococcal superantigen-specific IgE antibodies: degree of sensitization and association with severity of asthma.

PubMed

Elabras, José; Mello, Fernanda Carvalho de Queiroz; Lupi, Omar; Bica, Blanca Elena Rios Gomes; Papi, José Angelo de Souza; França, Alfeu Tavares

2016-01-01

To determine the presence of staphylococcal superantigen-specific IgE antibodies and degree of IgE-mediated sensitization, as well as whether or not those are associated with the severity of asthma in adult patients. This was a cross-sectional study involving outpatients with asthma under treatment at a tertiary care university hospital in the city of Rio de Janeiro, Brazil. Consecutive patients were divided into two groups according to the severity of asthma based on the Global Initiative for Asthma criteria: mild asthma (MA), comprising patients with mild intermittent or persistent asthma; and moderate or severe asthma (MSA). We determined the serum levels of staphylococcal toxin-specific IgE antibodies, comparing the results and performing a statistical analysis. The study included 142 patients: 72 in the MA group (median age = 46 years; 59 females) and 70 in the MSA group (median age = 56 years; 60 females). In the sample as a whole, 62 patients (43.7%) presented positive results for staphylococcal toxin-specific IgE antibodies: staphylococcal enterotoxin A (SEA), in 29 (20.4%); SEB, in 35 (24.6%); SEC, in 33 (23.2%); and toxic shock syndrome toxin (TSST), in 45 (31.7%). The mean serum levels of IgE antibodies to SEA, SEB, SEC, and TSST were 0.96 U/L, 1.09 U/L, 1.21 U/L, and 1.18 U/L, respectively. There were no statistically significant differences between the two groups in terms of the qualitative or quantitative results. Serum IgE antibodies to SEA, SEB, SEC, and TSST were detected in 43.7% of the patients in our sample. However, neither the qualitative nor quantitative results showed a statistically significant association with the clinical severity of asthma. Determinar a presença de anticorpos IgE específicos para superantígenos estafilocócicos e o grau de sensibilização mediada por esses, assim como se esses estão associados à gravidade da asma em pacientes adultos. Estudo transversal incluindo asmáticos adultos em acompanhamento ambulatorial em

Food-specific serum IgE and IgG reactivity in dogs with and without skin disease: lack of correlation between laboratories.

PubMed

Hardy, Jonathan I; Hendricks, Anke; Loeffler, Anette; Chang, Yu-Mei; Verheyen, Kristien L; Garden, Oliver A; Bond, Ross

2014-10-01

Despite conflicting data on their utility and no reports on interlaboratory reproducibility, serum food-specific antibodies are commonly assayed in first-opinion canine practice. To determine both the variability of test results between two laboratories and the frequencies and magnitudes of food reactivity in dogs of different disease status. Sera were obtained from eight dogs with cutaneous adverse food reaction (Group A), 22 with nonfood-induced atopic dermatitis (Group B), 30 with an allergic/inflammatory phenotype (Group C), 12 with miscellaneous skin diseases (Group D) and nine healthy dogs (Group E). Paired sera were submitted to two laboratories (A and B) for assays of food-specific IgE and IgG antibodies. Numbers of positive IgE and IgG tests determined by each laboratory in Groups A, B, D and E were comparable (Group C not included). Significant differences in the magnitude of IgE reactivity between groups for each allergen were seen only for lamb (Laboratory A, P = 0.003); lamb reactivity in Group D exceeded Group E (P = 0.004) but was comparable between all other groups. Agreement (kappa statistic) between the two laboratories' tests was 'moderate' for one antigen (potato IgE), 'fair' for four (corn IgE, rice IgE and IgG and soya bean IgG), 'slight' for eight (six IgE and two IgG) and 'less than chance' for the remaining six antigens (three IgE and three IgG). These laboratories' tests appear to have dubious predictive clinical utility because they neither correlate nor distinguish between dogs of different disease status. © 2014 ESVD and ACVD.

Anaphylaxis to pork kidney is related to IgE antibodies specific for galactose-alpha-1,3-galactose.

PubMed

Morisset, M; Richard, C; Astier, C; Jacquenet, S; Croizier, A; Beaudouin, E; Cordebar, V; Morel-Codreanu, F; Petit, N; Moneret-Vautrin, D A; Kanny, G

2012-05-01

Carbohydrate-specific IgE antibodies present on nonprimate mammalian proteins were incriminated recently in delayed meat anaphylaxis. The aim of this study was to explore whether anaphylaxis to mammalian kidney is also associated with galactose-α-1,3-galactose (αGal)-specific IgE. Fourteen patients with anaphylaxis to pork or beef kidney underwent prick tests to meat and kidney. Some patients also underwent skin tests to Erbitux(®) (cetuximab). IgE antibodies to αGal, swine urine proteins, beef and pork meat, serum albumin proteins, cat, and rFel d 1 were measured by ImmunoCAP(®). The αGal levels were estimated in meats and kidney by ELISA inhibition assay. Cross-reactivity between αGal and pork kidney was studied with the ImmunoCAP(®) inhibition assay. Among the 14 patients, 12 presented with anaphylactic shock. Reactions occurred within 2 h from exposure in 67% of patients. Associated risk factors were observed in 10 cases, and alcohol was the main cofactor. Three patients underwent an oral challenge to pork kidney, and anaphylaxis occurred after ingestion of small quantities (1-2 g). Prick tests to kidney were positive in 54% of patients. All tested patients showed positive skin tests to Erbitux(®). All patients tested positive for IgE to αGal, with levels ranging from 0.4 to 294 kU/l. IgE binding to αGal was inhibited by raw pork kidney extract (mean, 77%; range, 55-87%), which showed a high amount of αGal determinants. Pork or beef kidney anaphylaxis is related to αGal IgE. Its peculiar severity could be due to an elevated content of αGal epitopes in kidney. © 2012 John Wiley & Sons A/S.

Aerobic Exercise Decreases Lung Inflammation by IgE Decrement in an OVA Mice Model.

PubMed

Camargo Hizume-Kunzler, Deborah; Greiffo, Flavia R; Fortkamp, Bárbara; Ribeiro Freitas, Gabriel; Keller Nascimento, Juliana; Regina Bruggemann, Thayse; Melo Avila, Leonardo; Perini, Adenir; Bobinski, Franciane; Duarte Silva, Morgana; Rocha Lapa, Fernanda; Paula Vieira, Rodolfo; Vargas Horewicz, Verônica; Soares Dos Santos, Adair Roberto; Cattelan Bonorino, Kelly

2017-06-01

Aerobic exercise (AE) reduces lung function decline and risk of exacerbations in asthmatic patients. However, the inflammatory lung response involved in exercise during the sensitization remains unclear. Therefore, we evaluated the effects of exercise for 2 weeks in an experimental model of sensitization and single ovalbumin-challenge. Mice were divided into 4 groups: mice non-sensitized and not submitted to exercise (Sedentary, n=10); mice non-sensitized and submitted to exercise (Exercise, n=10); mice sensitized and exposed to ovalbumin (OVA, n=10); and mice sensitized, submitted to exercise and exposed to OVA (OVA+Exercise, n=10). 24 h after the OVA/saline exposure, we counted inflammatory cells from bronchoalveolar fluid (BALF), lung levels of total IgE, IL-4, IL-5, IL-10 and IL-1ra, measurements of OVA-specific IgG1 and IgE, and VEGF and NOS-2 expression via western blotting. AE reduced cell counts from BALF in the OVA group (p<0.05), total IgE, IL-4 and IL-5 lung levels and OVA-specific IgE and IgG1 titers (p<0.05). There was an increase of NOS-2 expression, IL-10 and IL-1ra lung levels in the OVA groups (p<0.05). Our results showed that AE attenuated the acute lung inflammation, suggesting immunomodulatory properties on the sensitization process in the early phases of antigen presentation in asthma. © Georg Thieme Verlag KG Stuttgart · New York.

Prevalence of serum IgE antibodies to the Staphylococcus aureus enterotoxins (SAE, SEB, SEC, SED, TSST-1) in patients with persistent allergic rhinitis.

PubMed

Rossi, Renato Enzo; Monasterolo, Giorgio

2004-03-01

Enterotoxins produced by Staphylococcus aureus and their specific IgE antibodies were thought to be important in worsening atopic dermatitis. However, few studies have documented an association between S. aureus or its exotoxins and exacerbations of upper airway/nasal disease. In the current study, we determined the prevalence of serum-specific IgE towards staphylococcal enterotoxin A, B, C, D (SEA, SEB, SEC, SED) and toxic shock syndrome toxin 1 (TSST-1) in patients suffering from rhinitis and/or asthma due to allergy. Therefore, we examined whether SEA, SEB, SEC, SED and TSST-1 were important in worsening the clinical status of patients allergic to house dust mites by means of assessing serum eosinophil cationic protein (ECP), which is thought to be a reliable marker of asthma and rhinitis severity. 198 patients with persistent allergic rhinitis and/or asthma due to house dust mites were evaluated. Specific IgE towards SEA, SEB, SEC, SED, TSST-1, timothy grass and birch pollen recombinant allergens, and other aeroallergen extracts from common allergen sources were evaluated by the Pharmacia CAP System. Serum ECP was assessed, too. The percentages of sensitization to staphylococcal enterotoxins of 198 house dust mite-allergic patients were as follows: TSST-1-specific IgE 24.7% (n=49), SEC-specific IgE 22.2% (n=44), SEB-specific IgE 15.1% (n=30), SEA-specific IgE 9.1% (n=18), and SED-specific IgE 5.5% (n=11). Out of 198 individuals allergic to house dust mites 136 patients suffering from persistent rhinitis were subdivided into two subgroups: 53 patients with serum-specific IgE to at least one staphylococcal enterotoxin and 83 patients without specific IgE towards staphylococcal enterotoxins. Patients sensitive to staphylococcal enterotoxins had higher serum ECP levels than patients lacking specific IgE to SEA, SEB, SEC, SED and TSST-1(geometric mean 24.3 vs. 16.6 microg/100 ml; p=0.029), as well as total IgE levels (geometric mean 564 vs. 161 kU/l, p=0.00063) and

Total serum IgE and parasite-specific IgG and IgA antibodies in human strongyloidiasis.

PubMed

Rossi, C L; Takahashi, E E; Partel, C D; Teodoro, L G; da Silva, L J

1993-01-01

Total serum IgE, and Strongyloides-specific IgG and IgA antibodies were studied in 27 patients with parasitologically proven strongyloidiasis. Clinical manifestations in this case series were investigated by a retrospective study of the patient's records. Total serum IgE levels were elevated (greater than 250 IU/ml) in 59% of the patients (mean concentration = 1364 IU/ml). Parasite-specific IgG and IgA antibodies were detected by ELISA in the serum of 23 (85.2%) and 21 (77.8%) patients, respectively. Elevated serum IgE and clinical manifestations were not useful indexes of the presence of strongyloidiasis. On the other hand, our results support the view that serologic tests, particularly ELISA for detecting Strongyloides-specific IgG antibodies, can be usefully exploited for diagnostic purposes in strongyloidiasis.

Different Results of IgE Binding- and Crosslinking-Based Allergy Tests Caused by Allergen Immobilization.

PubMed

Okamoto-Uchida, Yoshimi; Nakamura, Ryosuke; Matsuzawa, Yumiko; Soma, Megumi; Kawakami, Hiroshi; Ishii-Watabe, Akiko; Nishimaki-Mogami, Tomoko; Teshima, Reiko; Saito, Yoshiro

2016-01-01

The physicochemical nature of allergen molecules differ from the liquid phase to the solid phase. However, conventional allergy tests are based on the detection of immunoglobulin (Ig)E binding to immobilized allergens. We recently developed an in vitro allergy testing method using a luciferase-reporting humanized rat mast cell line to detect IgE crosslinking-induced luciferase expression (EXiLE test). The aim of the present study was to evaluate the effects of antigen immobilization on the results of different in vitro allergy tests using two anti-ovalbumin (OVA) antibodies (Abs), E-C1 and E-G5, with different properties in the OVA-induced allergic reaction. Both Abs showed clear binding to OVA with an enzyme-linked immunosorbent assay and by BIAcore analysis. However, only E-C1 potentiated EXiLE response for the liquid-phase OVA. On the other hand, OVA immobilized on solid-phase induced EXiLE responses in both E-C1 Ab- and E-G5 Ab-sensitized mast cells. Western blotting of OVA indicated that E-C1 Ab binds both to OVA monomers and dimers, unlike E-G5 Ab, which probably binds only to the OVA dimer. These results suggest that antigen immobilization enhanced IgE crosslinking ability through multimerization of allergen molecules in the solid phase, resulting in an increase in false positives in IgE binding-based conventional in vitro allergy tests. These findings shed light on the physicochemical nature of antigens as an important factor for the development and evaluation of in vitro allergy tests and suggest that mast cell activation-based allergy testing with liquid-phase allergens is a promising strategy to evaluate the physiological interactions of IgE and allergens.

Rapid desensitization induces internalization of antigen-specific IgE on mouse mast cells

PubMed Central

Oka, Tatsuya; Rios, Eon J.; Tsai, Mindy; Kalesnikoff, Janet; Galli, Stephen J.

2013-01-01

Background Rapid desensitization transiently prevents severe allergic reactions, allowing administration of life-saving therapies in previously sensitized patients. However, the mechanisms underlying successful rapid desensitization are not fully understood. Objectives We sought to investigate whether the mast cell (MC) is an important target of rapid desensitization in mice sensitized to exhibit IgE-dependent passive systemic anaphylaxis in vivo and to investigate the antigen specificity and underlying mechanisms of rapid desensitization in our mouse model. Methods C57BL/6 mice (in vivo) or primary isolated C57BL/6 mouse peritoneal mast cells (PMCs; in vitro) were passively sensitized with antigen-specific anti–2,4-dinitrophenyl IgE, anti-ovalbumin IgE, or both. MCs were exposed over a short period of time to increasing amounts of antigen (2,4-dinitrophenyl–human serum albumin or ovalbumin) in the presence of extracellular calcium in vitro or by means of intravenous administration to sensitized mice in vivo before challenging the mice with or exposing the PMCs to optimal amounts of specific or irrelevant antigen. Results Rapidly exposing mice or PMCs to progressively increasing amounts of specific antigen inhibited the development of antigen-induced hypothermia in sensitized mice in vivo and inhibited antigen-induced PMC degranulation and prostaglandin D2 synthesis in vitro. Such MC hyporesponsiveness was induced antigen-specifically and was associated with a significant reduction in antigen-specific IgE levels on MC surfaces. Conclusions Rapidly exposing MCs to progressively increasing amounts of antigen can both enhance the internalization of antigen-specific IgE on the MC surface and also desensitize these cells in an antigen-specific manner in vivo and in vitro. PMID:23810240

IgE in the diagnosis and treatment of allergic disease

PubMed Central

Platts-Mills, Thomas A. E.; Schuyler, Alexander J.; Erwin, Elizabeth A.; Commins, Scott P.; Woodfolk, Judith A.

2017-01-01

Traditionally, the concept of allergy implied an abnormal response to an otherwise benign agent (eg, pollen or food), with an easily identifiable relationship between exposure and disease. However, there are syndromes in which the relationship between exposure to the relevant allergen and the “allergic” disease is not clear. In these cases the presence of specific IgE antibodies can play an important role in identifying the relevant allergen and provide a guide to therapy. Good examples include chronic asthma and exposure to perennial indoor allergens and asthma related to fungal infection. Finally, we are increasingly aware of forms of food allergy in which the relationship between exposure and the disease is delayed by 3 to 6 hours or longer. Three forms of food allergy with distinct clinical features are now well recognized. These are (1) anaphylactic sensitivity to peanut, (2) eosinophilic esophagitis related to cow’s milk, and (3) delayed anaphylaxis to red meat. In these syndromes the immunology of the response is dramatically different. Peanut and galactose α-1,3-galactose (alpha-gal) are characterized by high- or very high-titer IgE antibodies for Ara h 2 and alpha-gal, respectively. By contrast, eosinophilic esophagitis is characterized by low levels of IgE specific for milk proteins with high- or very high-titer IgG4 to the same proteins. The recent finding is that patients with alpha-gal syndrome do not have detectable IgG4 to the oligosaccharide. Thus the serum results not only identify relevant antigens but also provide a guide to the nature of the immune response. PMID:27264001

Sesame allergy: role of specific IgE and skin-prick testing in predicting food challenge results.

PubMed

Permaul, Perdita; Stutius, Lisa M; Sheehan, William J; Rangsithienchai, Pitud; Walter, Jolan E; Twarog, Frank J; Young, Michael C; Scott, Jordan E; Schneider, Lynda C; Phipatanakul, Wanda

2009-01-01

There are conflicting data regarding the diagnostic value of sesame-specific IgE and sesame skin test. Currently, there are no established thresholds that predict clinical reactivity. We examined the correlation of sesame ImmunoCAP and skin-prick test (SPT) results with oral challenge outcomes in children suspected of having a sesame food allergy. We conducted a retrospective chart review of children, aged 2-12 years, receiving a sesame ImmunoCAP level, SPT, and food challenge from January 2004 to August 2008 at Children's Hospital Boston and affiliated allergy clinics. Food challenges were conducted in cases of questionable clinical history or a negative ImmunoCAP and/or negative SPT despite a convincing history. Thirty-three oral sesame challenges were conducted. Of the 33 challenges performed, 21% (n = 7) failed and 79% (n = 26) passed. A sesame-specific IgE level of > or = 7 kU(A)/L showed specificity of >90%. An SPT wheal size of > or = 6 mm showed specificity of >90%. Receiver operator characteristic (ROC) curve analysis for sesame-specific IgE revealed an area under the curve (AUC) of 0.56. ROC curve analysis for SPT wheal size revealed an AUC of 0.67. To our knowledge, this study represents the largest number of sesame challenges performed to evaluate the diagnostic value of both sesame-specific IgE and SPT. Based on our sample, both tests are not good predictors of true sesame allergy as determined by an oral challenge. We were unable to establish a threshold with a 95% positive predictive value for both sesame-specific IgE and SPT.

Relationships between skin test, specific IgE and levels of cytokines in patients with penicillin allergy.

PubMed

Qiao, H-L; Liu, J-H; Yang, J; Dong, Z-M

2005-08-01

The aim of this study was to investigate the relationships between skin test, specific immunoglobulin (Ig) E and cytokines in penicillin allergy. We collected the sera of 259 patients with historical positive skin test to penicillins, with immediate positive skin test and with a negative skin test results. The positive rate of specific IgE antibodies in 259 patients was 62.2% (161) by using radioallergosorbent test (RAST). Of the eight kinds of antigenic determinants, the positive rates of specific IgE to major and minor determinants were 43.63% (113) and 52.51% (136), respectively (p < 0.05). In 122 patients with immediate positive skin test, when the degrees of skin test were +, 2+, 3+ and 4+, the positive rates of specific IgE were 45.7, 57.1, 85.2 and 100%, respectively. The levels of interleukin (IL)-4, IL-13 and interferon (IFN)-gamma in the sera of patients with positive skin test were significantly increased with the degree of positive skin test (p < 0.05). The combined use of major and minor determinants in RAST offers the better test for the detection of penicillin-specific IgE antibodies. IL-4, IL-13 and IFN-gamma play important roles in penicillin allergy.

Genetic diversity in two introduced biofouling amphipods (Amphipods valida and Jassa marmorata) along the Pacific North American coast: investigation into molecular identification and cryptic diversity

EPA Science Inventory

We investigated patterns of genetic diversity among invasive populations of A. valida and J. marmorata from the Pacific North American coast to assess the accuracy of morphological identification and determine whether or not cryptic diversity and multiple introductions contribute...

IgE antibodies in relation to prevalence and multimorbidity of eczema, asthma, and rhinitis from birth to adolescence.

PubMed

Ballardini, N; Bergström, A; Wahlgren, C-F; van Hage, M; Hallner, E; Kull, I; Melén, E; Antó, J M; Bousquet, J; Wickman, M

2016-03-01

Eczema, asthma, and rhinitis affect a large proportion of children, but their prevalence varies with age. IgE antibodies are also common in the pediatric population. However, the links between IgE, disease, and trajectories are unclear. To better understand the links between sensitization and disease, we studied IgE sensitization ever in relation to eczema, asthma, and rhinitis, in children followed up to 16 years of age. From the Swedish population-based birth cohort BAMSE, 2607 children were included. Parental reports from six time points between 1 and 16 years were used to identify children with eczema, asthma, and rhinitis. Blood was collected at 4, 8, and 16 years, and sensitization ever was defined as allergen-specific IgE ≥0.35 kUA /l to common food and/or inhalant allergens at any time point. Odds ratios for eczema, asthma, rhinitis, and multimorbidity in relation to sensitization ever were calculated using generalized estimating equations. Fifty-one percent were sensitized at least once up to 16 years. Almost a quarter of ever-sensitized children did not have any disease. After adjustment for potential confounders, sensitization ever was significantly associated with the following: (i) eczema throughout childhood, (ii) multimorbidity of eczema, asthma, and rhinitis from 1 to 16 years (OR for multimorbidity: 5.11, 95% CI: 3.99-6.55), (iii) asthma and rhinitis from 4 to 16 years of age. Specific IgE is strongly associated with eczema and allergic multimorbidity throughout childhood and with asthma and rhinitis from age 4 years. However, 23% of the children with IgE sensitization do not develop any disease in childhood. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A study of the prevalence and clinical significance of venom-specific IgE.

PubMed

Zora, J A; Swanson, M C; Yunginger, J W

1988-01-01

The prevalence of unrecognized Hymenoptera-venom sensitization, assessed by venom skin tests (VSTs) in adults with no history of adverse reactions to sting, has been as high as 12% in previous epidemiologic studies. To assess further the clinical importance of positive VSTs in such individuals, we skin tested 33 subjects stung in the field during the preceding 12 months without reaction, and 33 persons who denied being stung in the preceding 3 years. Among the recently stung group, 12/33 had at least one positive VST (greater than or equal to 2+) at 1.0 microgram/ml, whereas 5/33 had positive VST at 0.1 microgram/ml. In contrast, only 2/33 nonstung subjects had positive VST at 1.0 microgram/ml, and none were positive at 0.1 microgram/ml. To estimate, prospectively, the sensitization rate after insect stings, we studied a third group of 11 nonsensitive patients with negative skin tests to Hymenoptera. After a deliberate in-hospital honeybee sting, only 1/11 developed a persistently positive honeybee VST. From among the three groups, we then performed nine sting challenges in eight patients with positive VSTs, and all stings were tolerated without significant reaction. We also measured IgE antibodies to Hymenoptera venoms in random blood bank donors. During April to May, 2/216 sera contained elevated venom-specific IgE antibodies, whereas 14/201 sera collected from October to November contained elevated venom-specific IgE antibodies. We conclude that a small but appreciable portion of the population has venom-specific IgE antibodies and that the prevalence is seasonably variable. Our data indicate that persons recently stung without significant reaction contribute to this group but that only a small portion of this group is at risk for a systemic reaction with a future sting.

Rapid desensitization induces internalization of antigen-specific IgE on mouse mast cells.

PubMed

Oka, Tatsuya; Rios, Eon J; Tsai, Mindy; Kalesnikoff, Janet; Galli, Stephen J

2013-10-01

Rapid desensitization transiently prevents severe allergic reactions, allowing administration of life-saving therapies in previously sensitized patients. However, the mechanisms underlying successful rapid desensitization are not fully understood. We sought to investigate whether the mast cell (MC) is an important target of rapid desensitization in mice sensitized to exhibit IgE-dependent passive systemic anaphylaxis in vivo and to investigate the antigen specificity and underlying mechanisms of rapid desensitization in our mouse model. C57BL/6 mice (in vivo) or primary isolated C57BL/6 mouse peritoneal mast cells (PMCs; in vitro) were passively sensitized with antigen-specific anti-2,4-dinitrophenyl IgE, anti-ovalbumin IgE, or both. MCs were exposed over a short period of time to increasing amounts of antigen (2,4-dinitrophenyl-human serum albumin or ovalbumin) in the presence of extracellular calcium in vitro or by means of intravenous administration to sensitized mice in vivo before challenging the mice with or exposing the PMCs to optimal amounts of specific or irrelevant antigen. Rapidly exposing mice or PMCs to progressively increasing amounts of specific antigen inhibited the development of antigen-induced hypothermia in sensitized mice in vivo and inhibited antigen-induced PMC degranulation and prostaglandin D2 synthesis in vitro. Such MC hyporesponsiveness was induced antigen-specifically and was associated with a significant reduction in antigen-specific IgE levels on MC surfaces. Rapidly exposing MCs to progressively increasing amounts of antigen can both enhance the internalization of antigen-specific IgE on the MC surface and also desensitize these cells in an antigen-specific manner in vivo and in vitro. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Development of allergy and IgE antibodies during the first five years of life in Estonian children.

PubMed

Julge, K; Vasar, M; Björkstén, B

2001-12-01

Epidemiological studies have demonstrated a low prevalence of allergic diseases and atopic sensitization among schoolchildren and young adults in the formerly socialist countries of Central and Eastern Europe as compared to Western Europe. The aim of our study was to prospectively investigate IgE responses to food and inhalant allergens and the development of allergy during early childhood in a population with a low prevalence of atopic disorders. In a population-based prospective study, 273 children were followed from birth through the first 5 years of life, recording manifestations of allergy by questionnaires and clinical examinations at 0.5, 1, 2 and 5 years (n = 213). Skin prick tests (SPT) were performed using natural foods (cow's milk, egg white) and commercial extracts of inhaled allergens (cat, dog, D. pteronyssinus, birch, timothy). In addition, serum IgE levels and circulating IgE antibodies against the seven allergens were determined. The prevalence of allergic diseases at 5 years of life was 19%. Atopic dermatitis was the most common allergic disease at all ages. The point prevalence of positive skin prick tests was 7% at 0.5, 1 and 2 years of age, and 3% at 5 years. Circulating IgE antibodies against food allergens were common at all ages, i.e. 13, 23, 36 and 36%, respectively, at 0.5, 1, 2 and 5 years. The prevalence of circulating IgE antibodies to inhalant allergens increased from 1.5% at 0.5 years to 11% at 1, 19% at 2 and 47% at 5 years. The antibody levels were generally low, however. The value of positive SPT and the presence of IgE antibodies in the diagnosis of clinical allergy were low. The results of this prospective study carried out in a previously socialist country with a low allergy prevalence among schoolchildren and young adults indicate that transient sensitization in early childhood is followed by a down-regulation of skin reactivity.

Rapid polyclonal desensitization with antibodies to IgE and FcεRIα.

PubMed

Khodoun, Marat V; Kucuk, Zeynep Yesim; Strait, Richard T; Krishnamurthy, Durga; Janek, Kevin; Lewkowich, Ian; Morris, Suzanne C; Finkelman, Fred D

2013-06-01

Rapid desensitization, a procedure in which persons allergic to an antigen are treated at short intervals with increasing doses of that antigen until they tolerate a large dose, is an effective, but risky, way to induce temporary tolerance. We wanted to determine whether this approach can be adapted to suppress all IgE-mediated allergies in mice by injecting serially increasing doses of monoclonal antibodies (mAbs) to IgE or FcεRIα. Active and passive models of antigen- and anti-IgE mAb-induced IgE-mediated anaphylaxis were used. Mice were desensitized with serially increasing doses of anti-IgE mAb, anti-FcεRIα mAb, or antigen. Development of shock (hypothermia), histamine and mast cell protease release, cytokine secretion, calcium flux, and changes in cell number and FcεRI and IgE expression were evaluated. Rapid desensitization with anti-IgE mAb suppressed IgE-mediated immediate hypersensitivity; however, some mice developed mild anaphylaxis during desensitization. Rapid desensitization with anti-FcεRIα mAb that only binds FcεRI that is not occupied by IgE suppressed both active and passive IgE-mediated anaphylaxis without inducing disease. It quickly, but temporarily, suppressed IgE-mediated anaphylaxis by decreasing mast cell signaling through FcεRI, then slowly induced longer lasting mast cell unresponsiveness by removing membrane FcεRI. Rapid desensitization with anti-FcεRIα mAb was safer and longer lasting than rapid desensitization with antigen. A rapid desensitization approach with anti-FcεRIα mAb safely desensitizes mice to IgE-mediated anaphylaxis by inducing mast cell anergy and later removing all mast cell IgE. Rapid desensitization with an anti-human FcεRIα mAb may be able to prevent human IgE-mediated anaphylaxis. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

IgE, IgG4 and IgA specific to Bet v 1-related food allergens do not predict oral allergy syndrome.

PubMed

Guhsl, E E; Hofstetter, G; Lengger, N; Hemmer, W; Ebner, C; Fröschl, R; Bublin, M; Lupinek, C; Breiteneder, H; Radauer, C

2015-01-01

Birch pollen-associated plant food allergy is caused by Bet v 1-specific IgE, but presence of cross-reactive IgE to related allergens does not predict food allergy. The role of other immunoglobulin isotypes in the birch pollen-plant food syndrome has not been investigated in detail. Bet v 1-sensitized birch pollen-allergic patients (n = 35) were diagnosed for food allergy by standardized interviews, skin prick tests, prick-to-prick tests and ImmunoCAP. Concentrations of allergen-specific IgE, IgG1, IgG4 and IgA to seven Bet v 1-related food allergens were determined by ELISA. Bet v 1, Cor a 1, Mal d 1 and Pru p 1 bound IgE from all and IgG4 and IgA from the majority of sera. Immunoglobulins to Gly m 4, Vig r 1 and Api g 1.01 were detected in <65% of the sera. No significant correlation was observed between plant food allergy and increased or reduced levels of IgE, IgG1, IgG4 or IgA specific to most Bet v 1-related allergens. Api g 1-specific IgE was significantly (P = 0.01) elevated in celeriac-allergic compared with celeriac-tolerant patients. Likewise, frequencies of IgE (71% vs 15%; P = 0.01) and IgA (86% vs 38%; P = 0.04) binding to Api g 1.01 were increased. Measurements of allergen-specific immunoglobulins are not suitable for diagnosing Bet v 1-mediated plant food allergy to hazelnut and Rosaceae fruits. In contrast, IgE and IgA to the distantly related allergen Api g 1 correlate with allergy to celeriac. © 2014 The Authors. Allergy Published by John Wiley & Sons Ltd.

Measurement of IgE antibodies using liquid allergens--an inter-method and inter-laboratory quality assessment.

PubMed

Aberer, Werner; Kränke, Birger

2002-11-30

The determination of IgE antibodies is important for the in vitro diagnosis of allergic diseases. However, not all systems currently available in the market fulfill essential quality criteria, e.g. regarding characteristics such as sensitivity and specificity, and the data do not always reflect true clinical relevance in the required fashion. Recent innovations may reduce the workload for the technician, and thus help save time and money. More importantly, they might reduce potential sources of error. Two allergy systems, the well established Pharmacia CAP system that uses the allergens conventionally in a solid phase and the ALLERgen system that employs liquid allergens, were compared with regard to quality criteria and practicability. Defined serum pools were checked for within-run and between-days imprecision of IgE antibody detection in two independent laboratories. Serum specimens from allergic patients and controls were tested in parallel using both methods for total and antigen-specific IgE antibody detection under standardized conditions. In addition, one laboratory working exclusively with the ALLERgen system participated in the Austrian inter-laboratory quality assessment program. The two systems were comparable in terms of sensitivity and specificity, and also showed good correlation. Within-run evaluations were excellent for total IgE and antigen-specific IgE, and the between-days imprecision was satisfactory. Coefficients of variation were within an acceptable range for the different groups of allergens. In the external quality control program the data obtained with the ALLERgen system showed good concordance with other systems in use; up to 94% of the results were identical when considering clinically relevant sensitizations. Regarding practicability, both systems were most satisfactory for the operator. The ALLERgen system offered a certain advantage in terms of automated operation, which resulted in shorter fixed and variable phases of personnel

Maternal Genetic Variants of IL4/IL13 Pathway Genes on IgE With "Western or Eastern Environments/Lifestyles".

PubMed

Zhang, Guicheng; Khoo, Siew-Kim; Mäkelä, Mika J; Candelaria, Pierre; Hayden, Catherine M; von Hertzen, Leena; Laatikainen, Tiina; Vartiainen, Erkki; Goldblatt, Jack; Haahtela, Tari; LeSouëf, Peter N

2014-07-01

We investigated maternal genetic effects of four IL-4/IL-13 pathway genes as well as their interactions with the "Western or Eastern lifestyles/environments" on IgE in Karelian children. This study included 609 children and their mothers. Total IgE levels in children and mothers were measured and 10 single nucleotide polymorphisms (SNPs) in IL-4, IL-4Ra, IL-13, and STAT6 were genotyped in mothers and their children. The maternal G allele of IL-13 130 (rs20541) was significantly (P=0.001) associated with decreased IgE in children in the Karelian population (Pooling Finnish and Russian children), as well as in Finnish (P=0.030) and Russian children (P=0.018). The IgE levels were significantly (P=0.001) higher in Russian children whose mothers were homozygous for the G allele of the IL-4Ra 50 (rs1805010) SNP than that in Russian children of mothers who were AG heterozygotes or AA homozygotes. After accounting for children's genotypes, we observed interactive effects on children's IgE for maternal IL-13 130 genotypes (P=0.014) and maternal IL-4Ra 50 genotypes (P=0.0003) with "Western or Eastern" lifestyles/environments. With the adjustment for multiple comparisons using a false discovery rate (FDR) of 0.05, the interactive effect of the maternal IL-4Ra50 SNP was significant. Maternal genetic variants in IL-4/IL-13 pathway genes, such as IL-13 130 and IL-4Ra50, influenced IgE levels in school children that were independent of the children's genetic effects. These effects differ in "Western or Eastern" environments.

Prevalence of IgE reactivities in mold-allergic subjects to commercially available fungal enzymes.

PubMed

Horner, W Elliott; Armstrong, Maricelis; El-Dahr, Jane; McCants, Marjorie; Reese, Gerald; Kobernick, Aaron K; Lehrer, Samuel B

2008-01-01

Fungi are important aeroallergens. However, fungal allergen sources of consistent quality for clinical testing are not readily available. Because some allergens have been identified as enzymes, we assessed the prevalence of IgE reactivity to commercially available fungal enzymes. The purpose of this study was to determine IgE antibody reactivity by radioallergosorbent assay (RAST) to commercially available fungal enzymes in mold-allergic individuals. Sera from 20 subjects with symptoms of respiratory allergies and skin test reactivity to 2 or more fungal allergens (4 conidial [imperfecti] fungi and/or 8 basidiomycetes) were selected. Controls were six atopic individuals with neither history of fungal allergy nor skin test reactivity to fungi. Seventeen commercial fungal enzymes were used as antigens to evaluate the subjects' IgE antibody reactivity by RAST. Sera from most fungus-allergic individuals showed substantial IgE antibody reactivity to enzymes; control sera showed little or no reactivity. The mean reactivity to all commercial enzymes of all subjects tested was RAST > or = 3% with only one exception. The most reactive fungal enzymes were invertase (bakers' yeast, Saccharomyces cerevisiae), cellulase (Trichoderma viride), and glucosidase (brewers yeast, S. cerevisiae) with mean binding of 14.6, 9.5, and 8.8%, respectively. Using RAST results with a combination of four enzymes from S. cerevisiae (brewers yeast glucosidase, bakers' yeast maltase, invertase, and invertase V), a sensitivity of 100% was shown for detecting mold-allergic patients. The studies suggest that fungal enzymes may be useful source materials for the identification of fungal allergens and may also provide readily available source materials to produce improved diagnostic and therapeutic reagents.

The clinical efficacy of in vitro allergen-specific IgE antibody test in the diagnosis of allergic children with asthma.

PubMed

Chou, Tzn-Yu; Wu, Kuo-Yao; Shieh, Chi-Chang; Wang, Jiu-Yao

2002-01-01

Asthma is a very common respiratory allergic disease in Taiwan. The aims of this study were to investigate the allergen-sensitized profile and its relationship with serum total IgE levels in allergic asthmatic children in Taiwan. Moreover, the number of allergens to be tested for the most efficient and effective diagnosis of allergic diseases was also examined. Total IgE and IgE specific for a panel of common aeroallergens were assayed in 200 serum samples of asthmatic children using Pharmacia CAP system (Pharmacia, Uppsala, Sweden). House dust mites Der p (Dermatophagoides pteronyssinus), Der f (Dermatophagoides farinae), and Bt (Blomia Tropicalis) had the highest sensitized rates at 82.5%, 82.0%, and 72%, respectively. Candida albican (14.0%) and Bermuda grass (8.0%) were the most common sensitized fungus and pollen in our subjects, respectively. The accumulated sensitized rate (10%) for pollens was lower than those of fungus (21.5%) and house dust allergens (84%). The average serum total IgE of the allergen-negative asthmatic children (n=30) was significantly lower than that of children with at least one allergen sensitized asthma (n=170) (377.9 +/- 123.6 vs. 1117.8 +/- 235.7 IU/ml, p<0.05). The level of total IgE was significantly correlated with the concentrations of mite-specific IgE antibodies, but not with the numbers of allergen sensitized. In addition, the detection rate was 84% when the 4 most common allergens (Der p, Der f, Dog dander, and cockroach) were tested, similar to the result after testing for all 12.

Food aversion: a critical balance between allergen-specific IgE levels and taste preference.

PubMed

Mirotti, Luciana; Mucida, Daniel; de Sá-Rocha, Luis Carlos; Costa-Pinto, Frederico Azevedo; Russo, Momtchilo

2010-03-01

Animals sensitized to allergens change their feeding behavior and avoid drinking the otherwise preferred sweetened solutions containing the allergens. This phenomenon, known as food aversion, appears to be mediated by allergen-specific IgE antibodies. Here we investigated food aversion in BALB/c and C57BL/6 mice, which differ in their allergic responses to the allergen ovalbumin as well as in their preference for sweet taste. BALB/c mice present higher levels of IgE and a natural lower preference for sweet flavors when compared to C57BL/6 mice. Specifically, we studied a conflicting situation in which animals simultaneously experienced the aversive contact with the allergen and the attractive sweet taste of increasing concentrations of sucrose. We found that BALB/c mice were more prone to develop food aversion than C57BL/6 mice and that this aversive behavior could be abolished in both strains by increasing the palatability of the solution containing the allergen. In both strains food aversion was positively correlated with the levels of allergen-specific IgE antibodies and inversely correlated with their preference for sucrose sweetened solutions. 2009 Elsevier Inc. All rights reserved.

IgE Inhibits Toll-like Receptor 7- and Toll-like Receptor 9-Mediated Expression of Interferon-α by Plasmacytoid Dendritic Cells in Patients With Systemic Lupus Erythematosus.

PubMed

Khoryati, Liliane; Augusto, Jean-François; Shipley, Emilie; Contin-Bordes, Cécile; Douchet, Isabelle; Mitrovic, Stéphane; Truchetet, Marie-Elise; Lazaro, Estibaliz; Duffau, Pierre; Couzi, Lionel; Jacquemin, Clément; Barnetche, Thomas; Vacher, Pierre; Schaeverbeke, Thierry; Blanco, Patrick; Richez, Christophe

2016-09-01

Plasmacytoid dendritic cells (PDCs) play a central role in pathogenesis of systemic lupus erythematosus (SLE) through their unique ability to produce large amounts of type I interferon (IFN) upon Toll-like receptor 7 (TLR-7) and TLR-9 triggering. PDCs express specific surface regulatory receptors involved in negative regulation of IFNα secretion. These receptors use the γ-chain of high-affinity Fc receptor (FcR) for IgE, FcɛRI. We undertook this study to test our hypothesis that IgE engagement of FcɛRI on PDCs may impact IFNα production in SLE patients. Serum levels of total IgE were measured in healthy volunteers, SLE patients, and patients with IgE-dependent allergic disorders. FcɛRI expression on PDCs from SLE patients was evaluated by flow cytometry. Purified PDCs were incubated with monoclonal IgE for 24 hours, then stimulated for 18 hours with TLR agonists or immune complexes (ICs). IFNα production by PDCs was detected by quantitative real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay. Expression of TLR-7, TLR-9, and IFN regulatory factor 7 (IRF-7) in PDCs was quantified by quantitative real-time PCR. We observed significantly higher IgE levels in SLE patients with quiescent disease than in those with active disease. In SLE patients, IgE levels correlated inversely with disease activity. IgE levels were not associated with the presence of antinuclear IgE. Purified PDCs treated for 24 hours with monoclonal IgE up-regulated FcɛRI expression in an IgE dose-dependent manner. IgE-treated PDCs significantly decreased IFNα secretion and down-regulated CCR7 expression upon stimulation with TLR-7 and TLR-9 ligands and ICs from lupus patients. IgE treatment down-regulated expression of TLR-9 and IRF-7. Our results support the notion that IgE plays a protective role in SLE pathogenesis through the modulation of inflammatory response by PDCs. © 2016, American College of Rheumatology.

Mast Cells and IgE can Enhance Survival During Innate and Acquired Host Responses to Venoms*

PubMed Central

GALLI, STEPHEN J.; STARKL, PHILIPP; MARICHAL, THOMAS; TSAI, MINDY

2017-01-01

Mast cells and immunoglobulin E (IgE) antibodies are thought to promote health by contributing to host responses to certain parasites, but other beneficial functions have remained obscure. Venoms provoke innate inflammatory responses and pathology reflecting the activities of the contained toxins. Venoms also can induce allergic sensitization and development of venom-specific IgE antibodies, which can predispose some subjects to exhibit anaphylaxis upon subsequent exposure to the relevant venom. We found that innate functions of mast cells, including degradation of venom toxins by mast cell–derived proteases, enhanced survival in mice injected with venoms from the honeybee, two species of scorpion, three species of poisonous snakes, or the Gila monster. We also found that mice injected with sub-lethal amounts of honeybee or Russell’s viper venom exhibited enhanced survival after subsequent challenge with potentially lethal amounts of that venom, and that IgE antibodies, FcεRI, and probably mast cells contributed to such acquired resistance. PMID:28790503

Application of immuno-PCR assay for the detection of serum IgE specific to Bermuda allergen.

PubMed

Rahmatpour, Samine; Khan, Amjad Hayat; Nasiri Kalmarzi, Rasoul; Rajabibazl, Masoumeh; Tavoosidana, Gholamreza; Motevaseli, Elahe; Zarghami, Nosratollah; Sadroddiny, Esmaeil

2017-04-01

In vivo and in vitro tests are the two major ways of identifying the triggering allergens in sensitized individuals with allergic symptoms. Both methods are equally significant in terms of sensitivity and specificity. However, in certain circumstances, in vitro methods are highly preferred because they circumvent the use of sensitizing drugs in patients. In current study, we described a highly sensitive immuno-PCR (iPCR) assay for serum IgE specific to Bermuda allergens. Using oligonucleotide-labelled antibody, we used iPCR for the sensitive detection of serum IgE. The nucleotide sequence was amplified using conventional PCR and the bands were visualized on 2.5% agarose gel. Results demonstrated a 100-fold enhancement in sensitivity of iPCR over commercially available enzyme-linked immunosorbent assay (ELISA) kit. Our iPCR method was highly sensitive for Bermuda-specific serum IgE and could be beneficial in allergy clinics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Omalizumab therapy in atopic dermatitis: depletion of IgE does not improve the clinical course - a randomized, placebo-controlled and double blind pilot study.

PubMed

Heil, Peter Maximilian; Maurer, Dieter; Klein, Brigitte; Hultsch, Thomas; Stingl, Georg

2010-12-01

Our understanding of the pathogenic role of IgE in atopic dermatitis is incomplete. We asked whether blocking free IgE would alter the course of the disease. We administered either omalizumab, a humanized monoclonal mouse antibody against IgE, or placebo subcutaneously for 16 weeks to 20 atopic dermatitis patients and measured immunological and clinical disease parameters. Omalizumab (I) reduced free serum IgE, (II) lowered surface IgE and FcɛRI expression on different peripheral blood mononuclear cells, (III) reduced the saturation of FcɛRI with IgE, (IV) increased the number of free FcɛRI and (V) lowered the number of IgE+, but not of FcɛRI+ cells in skin. The in vivo relevance of these results is evidenced by the increase in the threshold allergen concentration required to give a type I hypersensitivity reaction in the titrated skin test. While not significantly altering the clinical disease parameters, omalizumab treatment led to an improvement of the atopy patch test results in single patients, i.e. an eczematous reaction upon epicutaneous allergen challenge. The interference with immediate and delayed type skin tests may imply that a therapeutic benefit of omalizumab treatment, if present at all, would be seen in patients with acute rather than chronic forms of the disease. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.

Specific IgE and IgG to gelatin in children with systemic cutaneous reactions to Japanese encephalitis vaccines.

PubMed

Sakaguchi, M; Miyazawa, H; Inouye, S

2001-06-01

Systemic allergic reactions to Japanese encephalitis (JE) vaccine that include urticaria, angioedema, and rash have been reported. In Japan, children who suffered from allergic immediate-type reactions to JE vaccine had antigelatin IgE in their sera. However, the immunologic mechanism of allergic nonimmediate-type reactions that consist of cutaneous signs appearing several hours or more after JE vaccination has not been defined. Serum samples were taken from 28 children who showed allergic nonimmediate-type cutaneous reactions to JE vaccine. Furthermore, serum samples were taken from 10 children who showed allergic immediate-type reactions with cutaneous signs and/or respiratory symptoms to JE vaccine. We have defined an immediate-type reaction as one occurring within 1 h after vaccination. Of 10 children who showed immediate-type reactions, all had antigelatin IgE and IgG. Of 28 children who showed systemic nonimmediate-type reactions, one had antigelatin IgE and nine (32%) had antigelatin IgG. The child who had antigelatin IgE showed urticaria 2 h after JE vaccination. These results suggest that some children who showed allergic nonimmediate-type reactions to JE vaccine were sensitized to gelatin.

Specific IgE and IgG measured by the MeDALL allergen-chip depend on allergen and route of exposure: The EGEA study.

PubMed

Siroux, Valérie; Lupinek, Christian; Resch, Yvonne; Curin, Mirela; Just, Jocelyne; Keil, Thomas; Kiss, Renata; Lødrup Carlsen, Karin; Melén, Erik; Nadif, Rachel; Pin, Isabelle; Skrindo, Ingebjørg; Vrtala, Susanne; Wickman, Magnus; Anto, Josep Maria; Valenta, Rudolf; Bousquet, Jean

2017-02-01

The nature of allergens and route and dose of exposure may affect the natural development of IgE and IgG responses. We sought to investigate the natural IgE and IgG responses toward a large panel of respiratory and food allergens in subjects exposed to different respiratory allergen loads. A cross-sectional analysis was conducted in 340 adults of the EGEA (Epidemiological study of the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy) (170 with and 170 without asthma) cohort. IgE and IgG responses to 47 inhalant and food allergen components were analyzed in sera using allergen microarray and compared between 5 French regions according to the route of allergen exposure (inhaled vs food allergens). Overall 48.8% of the population had allergen-specific IgE levels of 0.3 ISAC standardized units (ISU) or more to at least 1 of the 47 allergens with no significant differences across the regions. For ubiquitous respiratory allergens (ie, grass, olive/ash pollen, house dust mites), specific IgE did not show marked differences between regions and specific IgG (≥0.5 ISU) was present in most subjects everywhere. For regionally occurring pollen allergens (ragweed, birch, cypress), IgE sensitization was significantly associated with regional pollen exposure. For airborne allergens cross-reacting with food allergens, frequent IgG recognition was observed even in regions with low allergen prevalence (Bet v 1) or for allergens less frequently recognized by IgE (profilins). The variability in allergen-specific IgE and IgG frequencies depends on exposure, route of exposure, and overall immunogenicity of the allergen. Allergen contact by the oral route might preferentially induce IgG responses. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Suppression of in vivo polyclonal IgE responses by monoclonal antibody to the lymphokine B-cell stimulatory factor 1.

PubMed Central

Finkelman, F D; Katona, I M; Urban, J F; Snapper, C M; Ohara, J; Paul, W E

1986-01-01

The lymphokine B-cell stimulatory factor 1 (BSF-1) has been shown to greatly enhance the differentiation of lipopolysaccharide-activated B cells into IgG1- and IgE-secreting cells in vitro. To determine whether in vivo IgG1 and IgE antibody responses are BSF-1 dependent, the ability of a monoclonal rat IgG1 anti-BSF-1 antibody, 11B11, to affect polyclonal IgG1 and IgE production in mice infected with the nematode parasite Nippostrongylus brasiliensis or injected with a purified goat antibody to mouse IgD was studied. 11B11-containing ascites fluid or purified 11B11 strongly inhibited IgE production in both systems but did not affect IgG1 production, while control ascites or normal rat IgG1 had no IgE-inhibitory activity. These results indicate an important physiologic role for BSF-1 in the generation of IgE antibody responses and suggest means for limiting the production of antibodies responsible for allergic reactions without inhibiting protective antibody responses. PMID:3491987

ABPA diagnosis in cystic fibrosis patients: the clinical utility of IgE specific to recombinant Aspergillus fumigatus allergens.

PubMed

Almeida, Marina B; Bussamra, Maria Helena C F; Rodrigues, Joaquim C

2006-01-01

Allergic bronchopulmonary aspergillosis (ABPA) is a complicating factor of cystic fibrosis which can result in a devastating combination as lung disease progresses. The overlap between the signs and symptoms of the two conditions makes diagnosis problematic, even if standardized criteria are used. The objective of this study was to identify, in a group of cystic fibrosis patients, cases of ABPA by assaying IgE specific to recombinant Aspergillus fumigatus antigens and to compare the method with the Cystic Fibrosis Foundation diagnostic criteria. Fifty-four patients, aged 2 to 20 years, presenting characteristics that could occur with ABPA in isolation, were systematically assessed based on the following: clinical data, a chest CT scan, immediate hypersensitivity skin test for A. fumigatus, total serum IgE assay, RAST for A. fumigatus and serum IgE specific for the recombinant allergens Asp f1, f2, f3, f4 and f6. Thirty-nine patients were eligible for the study. Thirty-two of these were investigated. Sensitization to A. fumigatus was observed in 34%. Both the Cystic Fibrosis Foundation criteria and the recombinant antigen specific IgE assay defined three patients as suffering from ABPA; however, only two of these patients were diagnosed by both methods. The detection of A. fumigatus recombinant antigen specific IgE was a useful tool for the early detection of sensitization and diagnosis of ABPA. Nevertheless, diagnostic confirmation cannot be divorced from clinical findings, and before this method can be used for ABPA diagnosis, for detecting relapses and for defining cure criteria, longitudinal studies with larger numbers of patients are required.

IgE and allergen-specific immunotherapy-induced IgG4 recognize similar epitopes of Bet v 1, the major allergen of birch pollen.

PubMed

Groh, N; von Loetzen, C S; Subbarayal, B; Möbs, C; Vogel, L; Hoffmann, A; Fötisch, K; Koutsouridou, A; Randow, S; Völker, E; Seutter von Loetzen, A; Rösch, P; Vieths, S; Pfützner, W; Bohle, B; Schiller, D

2017-05-01

Allergen-specific immunotherapy (AIT) with birch pollen generates Bet v 1-specific immunoglobulin (Ig)G 4 which blocks IgE-mediated hypersensitivity mechanisms. Whether IgG 4 specific for Bet v 1a competes with IgE for identical epitopes or whether novel epitope specificities of IgG 4 antibodies are developed is under debate. We sought to analyze the epitope specificities of IgE and IgG 4 antibodies from sera of patients who received AIT. 15 sera of patients (13/15 received AIT) with Bet v 1a-specific IgE and IgG 4 were analyzed. The structural arrangements of recombinant (r)Bet v 1a and rBet v 1a _11x , modified in five potential epitopes, were analyzed by circular dichroism and nuclear magnetic resonance spectroscopy. IgE binding to Bet v 1 was assessed by ELISA and mediator release assays. Competitive binding of monoclonal antibodies specific for Bet v 1a and serum IgE/IgG 4 to rBet v 1a and serum antibody binding to a non-allergenic Bet v 1-type model protein presenting an individual epitope for IgE was analyzed in ELISA and western blot. rBet v 1a _11x had a Bet v 1a - similar secondary and tertiary structure. Monomeric dispersion of rBet v 1a _11x was concentration and buffer-dependent. Up to 1500-fold increase in the EC 50 for IgE-mediated mediator release induced by rBet v 1a _11x was determined. The reduction of IgE and IgG 4 binding to rBet v 1a _11x was comparable in 67% (10/15) of sera. Bet v 1a-specific monoclonal antibodies inhibited binding of serum IgE and IgG 4 to 66.1% and 64.9%, respectively. Serum IgE and IgG 4 bound specifically to an individual epitope presented by our model protein in 33% (5/15) of sera. Patients receiving AIT develop Bet v 1a-specific IgG 4 which competes with IgE for partly identical or largely overlapping epitopes. The similarities of epitopes for IgE and IgG 4 might stimulate the development of epitope-specific diagnostics and therapeutics. © 2016 John Wiley & Sons Ltd.

Use of Humanized RS-ATL8 Reporter System for Detection of Allergen-Specific IgE Sensitization in Human Food Allergy.

PubMed

Ali, Eman Ali; Nakamura, Ryosuke; Falcone, Franco H

2017-01-01

Allergen-specific Immunoglobulin E (IgE) determination lies at the heart of diagnosis of sensitization to food and other allergens. In the past few years, reporter systems capable of detecting the presence of allergen-specific IgE have been developed by several labs. These rely on humanized rat basophil leukemia cell lines stably transfected with reporter genes such as firefly luciferase. In this chapter, we describe protocols for the use of the RS-ATL8 cell line (IgE cross-linking-induced luciferase expression; EXiLE) in 96-well and 384-well formats. We also describe optional treatment steps for enveloped virus and complement inactivation.

Heat-induced alterations in cashew allergen solubility and IgE binding

USDA-ARS?s Scientific Manuscript database

Cashew nuts are included in a group of 8 foods that commonly cause food allergies. IgE binding to allergens within the nuts can cause allergic reactions that can be severe. Foods containing cashew nuts must be labeled to prevent accidental exposure to people who suffer from allergy to cashew nuts....

Role of specific IgE and skin-prick testing in predicting food challenge results to baked egg

PubMed Central

Cortot, Catherine F.; Sheehan, William J.; Permaul, Perdita; Friedlander, James L.; Baxi, Sachin N.; Gaffin, Jonathan M.; Dioun, Anahita F.; Hoffman, Elaine B.; Schneider, Lynda C.

2012-01-01

Previous studies suggest that children with egg allergy may be able to tolerate baked egg. Reliable predictors of a successful baked egg challenge are not well established. We examined egg white–specific IgE levels, skin-prick test (SPT) results, and age as predictors of baked egg oral food challenge (OFC) outcomes. We conducted a retrospective chart review of children, aged 2–18 years, receiving an egg white–specific IgE level, SPT, and OFC to baked egg from 2008 to 2010. Fifty-two oral baked egg challenges were conducted. Of the 52 challenges, 83% (n = 43) passed and 17% (n = 9) failed, including 2 having anaphylaxis. Median SPT wheal size was 12 mm (range, 0–35 mm) for passed challenges and 17 mm (range, 10–30 mm) for failed challenges (p = 0.091). The negative predictive value for passing the OFC was 100% (9 of 9) if SPT wheal size was <10 mm. Median egg white–specific IgE was 2.02 kU/L (range, <0.35–13.00 kU/L) for passed challenges and 1.52 kU/L (range, 0.51–6.10 kU/L) for failed challenges (p = 0.660). Receiver operating characteristic (ROC) curve analysis for SPT revealed an area under the curve (AUC) of 0.64. ROC curve analysis for egg white–specific IgE revealed an AUC of 0.63. There was no significant difference in age between patients who failed and those who passed (median = 8.8 years versus 7.0 years; p = 0.721). Based on our sample, SPT, egg white–specific IgE and age are not good predictors of passing a baked egg challenge. However, there was a trend for more predictability with SPT wheal size. PMID:22584194

Role of specific IgE and skin-prick testing in predicting food challenge results to baked egg.

PubMed

Cortot, Catherine F; Sheehan, William J; Permaul, Perdita; Friedlander, James L; Baxi, Sachin N; Gaffin, Jonathan M; Dioun, Anahita F; Hoffman, Elaine B; Schneider, Lynda C; Phipatanakul, Wanda

2012-01-01

Previous studies suggest that children with egg allergy may be able to tolerate baked egg. Reliable predictors of a successful baked egg challenge are not well established. We examined egg white-specific IgE levels, skin-prick test (SPT) results, and age as predictors of baked egg oral food challenge (OFC) outcomes. We conducted a retrospective chart review of children, aged 2-18 years, receiving an egg white-specific IgE level, SPT, and OFC to baked egg from 2008 to 2010. Fifty-two oral baked egg challenges were conducted. Of the 52 challenges, 83% (n = 43) passed and 17% (n = 9) failed, including 2 having anaphylaxis. Median SPT wheal size was 12 mm (range, 0-35 mm) for passed challenges and 17 mm (range, 10-30 mm) for failed challenges (p = 0.091). The negative predictive value for passing the OFC was 100% (9 of 9) if SPT wheal size was <10 mm. Median egg white-specific IgE was 2.02 kU/L (range, <0.35-13.00 kU/L) for passed challenges and 1.52 kU/L (range, 0.51-6.10 kU/L) for failed challenges (p = 0.660). Receiver operating characteristic (ROC) curve analysis for SPT revealed an area under the curve (AUC) of 0.64. ROC curve analysis for egg white-specific IgE revealed an AUC of 0.63. There was no significant difference in age between patients who failed and those who passed (median = 8.8 years versus 7.0 years; p = 0.721). Based on our sample, SPT, egg white-specific IgE and age are not good predictors of passing a baked egg challenge. However, there was a trend for more predictability with SPT wheal size.

The prevalence and diagnostic value of specific IgE antibodies to inhalant, animal and plant food, and ficus allergens in patients with natural rubber latex allergy.

PubMed

Ebo, D G; Bridts, C H; Hagendorens, M M; De Clerck, L S; Stevens, W J

2003-01-01

It is well recognised that natural rubber latex allergy can be associated with serological cross-reactivity to plant allergens, especially tropical fruits and Ficus. In contrast, data on the frequency and clinical value of specific IgE antibodies against these allergens remain rare. In addition, little is known about the prevalence and diagnostic value of specific IgE antibodies to classical inhalant and animal allergens in NRL allergic patients. The purpose of this study was to investigate the prevalence, the sensitivity, and the specificity of these different specific IgE antibodies in patients suffering from NRL allergy. Serum samples of 42 NRL allergic adults were investigated. All had a history of NRL allergy confirmed by a positive skin test for latex and a positive latex-specific IgE. Samples were analysed for IgE antibodies against 9 plant food allergens (avocado, banana, chestnut, fig, kiwi, papaya, peanut, pineapple and tomato) and Ficus benjamina. A specific IgE quantification for 3 animal food allergens (codfish, cow's milk, egg's white) and 8 common inhalant allergens (Dermatophagoïdes pteronyssinus, birch pollen, timothy grass pollen, mugwort pollen, cat and dog epithelium, Aspergillus fumigatus and Cladosporium herbarum) was also performed. Because double blind placebo-controlled challenges could not be considered, for ethical reasons, patient's food allergy or immediate hypersensitivity for Ficus and inhalant allergens was documented by a standardised questionnaire. Diagnosis of atopy was based on a relevant history and the presence of a specific IgE antibody to at least one classical inhalant allergen. For some IgE determinations presence or absence of cross-reactivity was investigated by CAP-inhibition tests. A specific IgE antibody to at least one of the investigated inhalant and animal food allergens was found in respectively 76% and 12% of the serum samples. A plant food-specific IgE antibody was observed in 88% of the serum samples, most

IgE reactivity to alpha1 and alpha2 chains of bovine type 1 collagen in children with bovine gelatin allergy.

PubMed

Sakaguchi, M; Hori, H; Hattori, S; Irie, S; Imai, A; Yanagida, M; Miyazawa, H; Toda, M; Inouye, S

1999-09-01

Anaphylactic reactions to measles, mumps, and rubella vaccines, including gelatin as a stabilizer, have been reported. It had been found that most of these reactions to live vaccines are caused by the bovine gelatin included in these vaccines. Gelatin mainly includes denatured type I collagen, which consists of alpha1 and alpha2 chains. The current study was designed to investigate the IgE reactivity to alpha1 and alpha2 chains of bovine type I collagen in gelatin-sensitive children. Serum samples were taken from 10 children who had anaphylaxis to the vaccines and high levels of specific IgE to bovine gelatin. Bovine type I collagen was isolated from bovine skin and then separated to alpha1 and alpha2 chains by column chromatography. IgE reactivity to denatured type I collagen and its alpha1 and alpha2 chains was analyzed by immunoblotting, ELISA, and histamine release from the mast cells passive sensitized with IgE antibodies in pooled serum of the children. All children had specific IgE to bovine type I collagen. Furthermore, IgE antibodies in their sera reacted with the alpha;2 chain but not with the alpha1 chain. Similarly, the mast cells sensitized with pooled sera in the children showed alpha2 chain-specific histamine release but not alpha1 chain-specific histamine release. In gelatin allergy denatured bovine type I collagen is a major allergen and IgE-binding sites exist in the alpha2 chain of type I collagen.

Evolution and predictive value of IgE responses toward a comprehensive panel of house dust mite allergens during the first 2 decades of life.

PubMed

Posa, Daniela; Perna, Serena; Resch, Yvonne; Lupinek, Christian; Panetta, Valentina; Hofmaier, Stephanie; Rohrbach, Alexander; Hatzler, Laura; Grabenhenrich, Linus; Tsilochristou, Olympia; Chen, Kuan-Wei; Bauer, Carl-Peter; Hoffman, Ute; Forster, Johannes; Zepp, Fred; Schuster, Antje; Wahn, Ulrich; Keil, Thomas; Lau, Susanne; Vrtala, Susanne; Valenta, Rudolf; Matricardi, Paolo Maria

2017-02-01

The evolution of the IgE response to the numerous allergen molecules of Dermatophagoides pteronyssinus is still unknown. We sought to characterize the evolutionary patterns of the IgE response to 12 molecules of D pteronyssinus from birth to adulthood and to investigate their determinants and clinical relevance. We investigated the clinical data and sera of 722 participants in the German Multicenter Allergy Study, a birth cohort started in 1990. Diagnoses of current allergic rhinitis (AR) related to mite allergy and asthma were based on yearly interviews at the ages of 1 to 13 years and 20 years. IgE to the extract and 12 molecules of D pteronyssinus were tested by means of ImmunoCAP and microarray technology, respectively, in sera collected at ages 1, 2, 3, 5, 6, 7, 10, 13, and 20 years. Exposure to mites at age 6 and 18 months was assessed by measuring Der p 1 weight/weight concentration in house dust. One hundred ninety-one (26.5%) of 722 participants ever had IgE to D pteronyssinus extract (≥0.35 kU A /L). At age 20 years, their IgE recognized most frequently Der p 2, Der p 1, and Der p 23 (group A molecules; prevalence, >40%), followed by Der p 5, Der p 7, Der p 4, and Der p 21 (group B molecules; prevalence, 15% to 30%) and Der p 11, Der p 18, clone 16, Der p 14, and Der p 15 (group C molecules; prevalence, <10%). IgE sensitization started almost invariably with group A molecules and expanded sequentially first to group B and finally to group C molecules. Early IgE sensitization onset, parental hay fever, and higher exposure to mites were associated with a broader polymolecular IgE sensitization pattern. Participants reaching the broadest IgE sensitization stage (ie, ABC) had significantly higher risk of mite-related AR and asthma than unsensitized participants. IgE to Der p 1 or Der p 23 at age 5 years or less predicted asthma at school age. Parental hay fever and early exposure to D pteronyssinus allergens promote IgE polysensitization to several

Protease-Activated Receptor-2 Activation Contributes to House Dust Mite-Induced IgE Responses in Mice

PubMed Central

Post, Sijranke; Heijink, Irene H.; Petersen, Arjen H.; de Bruin, Harold G.; van Oosterhout, Antoon J. M.; Nawijn, Martijn C.

2014-01-01

Aeroallergens such as house dust mite (HDM), cockroach, and grass or tree pollen are innocuous substances that can induce allergic sensitization upon inhalation. The serine proteases present in these allergens are thought to activate the protease-activated receptor (PAR)-2, on the airway epithelium, thereby potentially inducing allergic sensitization at the expense of inhalation tolerance. We hypothesized that the proteolytic activity of allergens may play an important factor in the allergenicity to house dust mite and is essential to overcome airway tolerance. Here, we aimed to investigate the role of PAR-2 activation in allergic sensitization and HDM-induced allergic airway inflammation. In our study, Par-2 deficient mice were treated with two different HDM extracts containing high and low serine protease activities twice a week for a period of 5 weeks. We determined airway inflammation through quantification of percentages of mononuclear cells, eosinophils and neutrophils in the bronchial alveolar lavage fluid and measured total IgE and HDM-specific IgE and IgG1 levels in serum. Furthermore, Th2 and pro-inflammatory cytokines including IL-5, IL-13, Eotaxin-1, IL-17, KC, Chemokine (C-C motif) ligand 17 (CCL17) and thymic stromal lymphopoietin (TSLP), were measured in lung tissue homogenates. We observed that independent of the serine protease content, HDM was able to induce elevated levels of eosinophils and neutrophils in the airways of both wild-type (WT) and Par-2 deficient mice. Furthermore, we show that induction of pro-inflammatory cytokines by HDM exposure is independent of Par-2 activation. In contrast, serine protease activity of HDM does contribute to enhanced levels of total IgE, but not HDM-specific IgE. We conclude that, while Par-2 activation contributes to the development of IgE responses, it is largely dispensable for the HDM-induced induction of pro-inflammatory cytokines and airway inflammation in an experimental mouse model of HDM

Effect of thermal processing on T cell reactivity of shellfish allergens - Discordance with IgE reactivity.

PubMed

Abramovitch, Jodie B; Lopata, Andreas L; O'Hehir, Robyn E; Rolland, Jennifer M

2017-01-01

Crustacean allergy is a major cause of food-induced anaphylaxis. We showed previously that heating increases IgE reactivity of crustacean allergens. Here we investigate the effects of thermal processing of crustacean extracts on cellular immune reactivity. Raw and cooked black tiger prawn, banana prawn, mud crab and blue swimmer crab extracts were prepared and IgE reactivity assessed by ELISA. Mass spectrometry revealed a mix of several allergens in the raw mud crab extract but predominant heat-stable tropomyosin in the cooked extract. PBMC from crustacean-allergic and non-atopic control subjects were cultured with the crab and prawn extracts and proliferation of lymphocyte subsets was analysed by CFSE labelling and flow cytometry. Effector responses were assessed by intracellular IL-4 and IFN-γ, and regulatory T (CD4+CD25+CD127loFoxp3+) cell proportions in cultures were also compared by flow cytometry. For each crustacean species, the cooked extract had greater IgE reactivity than the raw (mud crab p<0.05, other species p<0.01). In contrast, there was a trend for lower PBMC proliferative responses to cooked compared with raw extracts. In crustacean-stimulated PBMC cultures, dividing CD4+ and CD56+ lymphocytes showed higher IL-4+/IFN-γ+ ratios for crustacean-allergic subjects than for non-atopics (p<0.01), but there was no significant difference between raw and cooked extracts. The percentage IL-4+ of dividing CD4+ cells correlated with total and allergen-specific IgE levels (prawns p<0.01, crabs p<0.05). Regulatory T cell proportions were lower in cultures stimulated with cooked compared with raw extracts (mud crab p<0.001, banana prawn p<0.05). In conclusion, cooking did not substantially alter overall T cell proliferative or cytokine reactivity of crustacean extracts, but decreased induction of Tregs. In contrast, IgE reactivity of cooked extracts was increased markedly. These novel findings have important implications for improved diagnostics, managing

[Serum IgE in Guinea Pigs Died of Anaphylactic Shock and Its Forensic Signifi- cance When the Guinea Pig Cannot be Timely Refrigerated].

PubMed

Su, Jun; Yu, Jian; Liu, Yong

2015-10-01

To investigate the serum IgE with various postmortem intervals (PMI) in guinea pigs due to sudden death from anaphylactic shock and to explore the effect of refrigeration of corpse on serum IgE level and its application value in forensic medicine. The animal death models of anaphylactic shock were established. The corpses were preserved at room temperature (20 °C ) for 6 h and then refrigerated at 4 °C. The serum was sampled at 6, 12, 24, 36 and 48 hours after death. The IgE level of serum was detected with ELISA. The control group was also established. The serum IgE level had significant. difference between the experimental group and the control group (P < 0.05). There was no significant difference among the experimental groups at 6, 12, 24, 36 and 48 hours post- mortem (P > 0.05). If the corpses were placed in 4 °C conditions 6 hours after anaphylactic death, the serum IgE still shows a good marker within 48 h for forensic investigation.

The absence of serum IgE antibodies indicates non-type 2 disease in young asthmatics.

PubMed

Tsolakis, N; Malinovschi, A; Nordvall, L; Janson, C; Borres, M P; Alving, K

2018-06-01

Atopic asthma is associated with elevated type-2 biomarkers such as fraction of exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) count. However, increased type 2 markers have also been reported in traditionally defined non-atopic asthma. To determine a clinically useful level of IgE sensitization for ruling out type 2 asthma. Asthmatics (N = 408; age 10-35 years) were analysed using the multi-allergen tests Phadiatop and fx5 (ImmunoCAP). Subjects were grouped based on IgE-antibody concentrations: ≥0.35 kU A /L for at least one test (n = 326) or <0.35 kU A /L for both tests (n = 82). Τhe latter group was subsequently divided into 2 groups: IgE 0.10-0.34 kU A /L (n = 34) and IgE < 0.10 kU A /L (n = 48). The relationships between type 2 biomarkers, and inadequate asthma control (ACT < 20), reduced lung function (FEV 1  < 80%), recent asthma attacks and airway hyperresponsiveness (AHR) to methacholine were determined. In univariate analyses, at least one type 2 marker related to each asthma outcome in subjects with IgE ≥0.35 kU A /L. In subjects with IgE 0.10-0.34 kU A /L, elevated FeNO related to reduced lung function (P = .008) and B-Eos to AHR (P = .03). No associations were found in subjects with IgE < 0.10 kU A /L. In multivariate analysis, a relationship between FeNO and reduced lung function remained in subjects with IgE < 0.35 kU A /L (P = .03). Clinically relevant elevation of type 2 biomarkers was seen in young asthmatics with IgE antibodies <0.35 kU A /L, but not those with IgE < 0.10 kU A /L. It seems possible to define non-type 2 asthma through sensitive IgE-antibody measurement. © 2018 John Wiley & Sons Ltd.

Evaluation of the IgE cross-reactions among vespid venoms. A possible approach for the choice of immunotherapy.

PubMed

Caruso, B; Bonadonna, P; Severino, M G; Manfredi, M; Dama, A; Schiappoli, M; Rizzotti, P; Senna, G; Passalacqua, G

2007-05-01

Hymenoptera venom allergy can be effectively cured with specific immunotherapy, thus the correct identification of the allergen is essential. In the case of multiple skin and serum positivities it is important to know if a cross-reaction among venoms is present. We studied by CAP-inhibition assays the degree of cross-reactivity between Vespula vulgaris and Polistes dominulus. Serum samples were obtained from consecutive patients with a clinical history of grade III-IV reactions to hymenoptera sting and with nondiscriminative skin/CAP positivity to both Vespula and Polistes. Inhibition assays were carried out with a CAP method, incubating the sera separately with both venoms and subsequently measuring the specific immunoglobulin E (IgE) to venoms themselves. Forty-five patients (33 male, mean age 40 years, age range 12-74, total serum IgE 242 +/- 168 kU/l) were included. Their specific IgE to Vespula and Polistes were 12.03 +/- 5.70 kU/l and 10.7 +/- 2.0 kU/l (P = NS), respectively. At the CAP-inhibition assays, in 25 patients a >75% heterologous inhibition by P. dominulus venom against V. vulgaris-specific IgE was found. In six subjects V. vulgaris venom effectively inhibited the P. dominulus-specific IgE. In the remaining 14 cases the CAP-inhibition test provided intermediate and not discriminative results. In 31/45 patients, the double sensitizations to venoms were probably the result of cross-reactions and the CAP-inhibition allowed identifying the true double sensitizations. This approach may be helpful for the correct prescription of immunotherapy in the case of V. vulgaris and P. dominulus double positivity.

Adjuvant activity of diesel-exhaust particulates for the production of IgE antibody in mice.

PubMed

Muranaka, M; Suzuki, S; Koizumi, K; Takafuji, S; Miyamoto, T; Ikemori, R; Tokiwa, H

1986-04-01

The prevalence rate of allergic rhinitis caused by pollen has strikingly increased in Japan in the last three decades. The number of diesel cars in use has also rapidly increased in the country. This fact urged us to study the effects of particulates emitted from diesel cars on the production of IgE antibody. The primary IgE antibody responses in mice immunized with intraperitoneal injection of ovalbumin (OA) mixed with diesel-exhaust particulates (DEP) were higher than those in the animals immunized with OA alone. This effect of DEP on the production of IgE antibody in mice was also demonstrated when mice were immunized with repeated injections of dinitrophenylated-OA. In addition, persistent IgE-antibody response to major allergen of Japanese cedar pollen (JCPA), a most common pollen causing allergic rhinitis in Japan, was observed in mice immunized with JCPA mixed with DEP but not in the animals immunized with JCPA alone. The results do indicate that the adjuvant activity of DEP can not be excluded as a possible cause of the associated change in the number of diesel cars and allergic rhinitis caused by pollen in Japan.

Correlation between hypersensitivity to parenteral chymopapain and the presence of IgE anti-chymopapain antibody.

PubMed Central

Kapsalis, A A; Stern, I J; Bornstein, I

1978-01-01

A solid phase radioimmunoassay, similar to the RAST, was developed in an attempt to predict anaphylactic reactions in patients injected with the proteolytic enzyme chymopapain, used in therapy for prolapsed intervertebral disc. The test measured the serum content of anti-chymopapain antibodies of the IgE class. Of 1263 patients tested, twelve gave anaphylactic reactions. The test was predictive for seven of them (58%), while sixty were false positives. Measurements were also made of anti-chymopapain IgE or other classes of antibodies which developed in the sera of patients after chymopapain injection. The presence of antibodies to chymopapain in individuals who had not been injected was also demonstrated. PMID:709910

Evaluation of IgE reactivity of active and thermally inactivated actinidin, a biomarker of kiwifruit allergy.

PubMed

Grozdanovic, Milica; Popovic, Milica; Polovic, Natalija; Burazer, Lidija; Vuckovic, Olga; Atanaskovic-Markovic, Marina; Lindner, Buko; Petersen, Arnd; Gavrovic-Jankulovic, Marija

2012-03-01

Actinidin, an abundant cysteine protease from kiwifruit, is a specific biomarker of isolated allergy to kiwifruit. This study evaluates the IgE-binding properties of biologically active and thermally inactivated actinidin. Employing two different activity assays (caseinolytic assay and zymogram with gelatin) we showed that actinidin obtained from kiwifruit extract under native conditions represents a mixture of inactive and active enzyme. The structural integrity of actinidin was confirmed by SDS-PAGE, Edman degradation, mass fingerprint and Western blot with polyclonal antibodies. Although it was capable of inducing positive skin prick test reactions, we failed to detect IgE reactivity of active actinidin in Western blot with patient sera. Thermally inactivated actinidin exhibited IgE reactivity both in vivo and in vitro, indicating that heat processed kiwifruit products may induce clinical reactivity. These findings imply that apart from the allergenic epitopes on its surface, actinidin also contains hidden epitopes inside the protein which become accessible to IgE upon thermal treatment. Copyright © 2011 Elsevier Ltd. All rights reserved.

Pyoderma gangrenosum in association with microscopic colitis, idiopathic hypereosinophilic syndrome, selective IgE deficiency and diabetes mellitus.

PubMed

Riyaz, N; Sasidharanpillai, S; Rahima, S; Bindu, V; Shaan, M; Raghavan, N T; Mohan, L; Janardhanan, A K

2015-08-01

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis of unknown aetiology. We report a 27-year-old male patient with diabetes, who presented with a nonhealing ulcer on the left leg, pruritic hyperpigmented papules distributed over the trunk and limbs, and chronic diarrhoea. He had eosinophilia, low haemoglobin and serum IgE levels, and raised erythrocyte sedimentation rate. Histopathology of the leg ulcer was consistent with the diagnosis of PG, while the histology of the hyperpigmented papule revealed tissue eosinophilia. Subsequent evaluation was conclusive of the diagnosis of PG, idiopathic hypereosinophilic syndrome (IHES) and selective IgE deficiency. Dexamethasone pulse therapy achieved resolution of the ulcer and reduction in the eosinophilia. Further evaluation for the persistent diarrhoea led to a diagnosis of lymphocytic colitis (LC), which responded to budesonide. To our knowledge, the association of PG with IHES, selective IgE deficiency or LC has not been previously reported. © 2015 British Association of Dermatologists.

Circulating CXCR5+CD4+ T cells participate in the IgE accumulation in allergic asthma.

PubMed

Gong, Fang; Zhu, Hua-Yan; Zhu, Jie; Dong, Qiao-Jing; Huang, Xuan; Jiang, Dong-Jin

2018-05-01

The pathogenesis of allergic asthma is primarily characterized by abnormality in immunoglobin(Ig)E pathway, suggesting a possible role for follicular helper T cells (Tfh) in the genesis of excessive IgE accumulation. The blood chemokine (C-X-C motif) receptor 5 (CXCR)5 + CD4 + T cells, known as "circulating" Tfh, share common functional characteristics with Tfh cells from germinal centers. The aim of this study was to determine the phenotypes and functions of circulating CXCR5 + CD4 + T cells in allergic asthmatics. Here we found the frequency of the circulating CXCR5 + CD4 + T cells was raised in allergic asthma compared with healthy control (HC). Phenotypic assays showed that activated circulating CXCR5 + CD4 + T cells display the key features of Tfh cells, including invariably coexpressed programmed cell death (PD)-1 and inducible costimulator (ICOS). The frequency of interleukin IL-4 + -, IL-21 + -producing CXCR5 + CD4 + T cells was increased in allergic asthma patients compared with HC. Furthermore, sorted circulating CXCR5 + CD4 + T cells from allergic asthma patients boosted IgE production in coculture assay which could be inhibited by IL-4 or IL-21 blockage. Interestingly, IL-4 + -, IL-21 + -CXCR5 + CD4 + T cells positively correlated with total IgE in the blood. Our data indicated that circulating CXCR5 + CD4 + T cells may have a significant role in facilitating IgE production in allergic asthma patients. Copyright © 2018 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Unscrambling Egg Allergy: The Diagnostic Value of Specific IgE Concentrations and Skin Prick Tests for Ovomucoid and Egg White in the Management of Children with Hen's Egg Allergy.

PubMed

Marriage, D E; Erlewyn-Lajeunesse, M; Unsworth, D J; Henderson, A J

2012-01-01

Resolution of egg allergy occurs in the majority of egg allergic children. Positive specific IgE antibodies to ovomucoid (OVM) have been suggested to be of greater predictive value for persistent egg allergy than specific IgE to egg white. The performance of OVM-specific IgE antibody levels in a cohort of children referred for a routine egg challenge was compared with egg white specific IgE levels in predicting a positive egg challenge. 24/47 subjects had persistent egg allergy. Receiver operating characteristic analysis showed that OVM-specific IgE testing was the most useful test for the diagnosis of persistent egg allergy. The optimal decision points for the prediction of persistent egg allergy were >0.35 kUA/L for specific IgE levels to both EW and OVM, and ≥3 mm for SPT. Children with specific IgE levels suggestive of persistent egg allergy need not be subject to an egg provocation challenge, reducing both costs and risks to the child.

Serum IgG and IgE antibodies against mold-derived antigens in patients with symptoms of hypersensitivity.

PubMed

Makkonen, K; Viitala, K I; Parkkila, S; Niemelä, O

2001-03-01

Exposure to mold in water-damaged buildings has been suggested to be responsible for various health problems such as hypersensitivity and upper respiratory tract diseases. However, only little information is available on possible diagnostic tools for examining mold-associated health problems. We used recently developed immunofluorometric IgG and IgE assays (UniCAP) to examine serum IgG and IgE antibodies against mold-derived allergens from 70 mold-exposed individuals with (n = 55) or without (n = 15) symptoms of sensitization. Controls were healthy individuals (n = 31) without any history of such exposure. The IgG titers exceeded the upper normal limits of control individuals (mean +/- 2 S.D.) in 35% of symptomatic men and in 25% of women. The IgG titers were usually higher in women than in men (P < 0.05) showing no significant association with the severity of symptoms. During follow-up of eight mold-exposed subjects for 9-12 months the IgG titers remained relatively constant. Elevated anti-mold IgEs were found in six (11%) of the exposed subjects who were all symptomatic. Measurements of anti-mold IgGs may help to confirm exposure in patients with hypersensitivity symptoms and evidence of mold growth in living or working environment. Some exposed symptomatic patients present IgE-mediated responses. Combined measurements of IgGs and IgEs may prove to be of value in the comprehensive assessment and treatment of such patients.

Influence of protein expression system on elicitation of IgE antibody responses: experience with lactoferrin.

PubMed

Almond, Rachael J; Flanagan, Brian F; Kimber, Ian; Dearman, Rebecca J

2012-11-15

With increased interest in genetically modified (GM) crop plants there is an important need to understand the properties that contribute to the ability of such novel proteins to provoke immune and/or allergic responses. One characteristic that may be relevant is glycosylation, particularly as novel expression systems (e.g. bacterial to plant) will impact on the protein glycoprofile. The allergenicity (IgE inducing) and immunogenicity (IgG inducing) properties of wild type native human lactoferrin (NLF) from human milk (hm) and neutrophil granules (n) and a recombinant molecule produced in rice (RLF) have been assessed. These forms of lactoferrin have identical amino acid sequences, but different glycosylation patterns: hmNLF and nNLF have complex glycoprofiles including Lewis (Le)(x) structures, with particularly high levels of Le(x) expressed by nNLF, whereas RLF is simpler and rich in mannose residues. Antibody responses induced in BALB/c strain mice by intraperitoneal exposure to the different forms of lactoferrin were characterised. Immunisation with both forms of NLF stimulated substantial IgG and IgE antibody responses. In contrast, the recombinant molecule was considerably less immunogenic and failed to stimulate detectable IgE, irrespective of endotoxin and iron content. The glycans did not contribute to epitope formation, with equivalent IgE and IgG binding recorded for high titre anti-NLF antisera regardless of whether the immunising NLF or the recombinant molecule were used substrates in the analyses. These data demonstrate that differential glycosylation profiles can have a profound impact on protein allergenicity and immunogenicity, with mannose and Le(x) exhibiting opposing effects. These results have clear relevance for characterising the allergenic hazards of novel proteins in GM crops. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Polyphenol-Rich Pomegranate Juice Reduces IgE Binding to Cashew Nut Allergens

USDA-ARS?s Scientific Manuscript database

Cashew nut allergy is mediated by IgE binding to seed-storage proteins including Ana o 1, 2, and 3. Cashew nuts commonly cause severe reactions and only small amounts are needed. Polyphenol rich juices and polyphenol compounds have been demonstrated to complex with peanut allergens. The interacti...

Evidence for a Peak Shift in a Humoral Response to Helminths: Age Profiles of IgE in the Shuar of Ecuador, the Tsimane of Bolivia, and the U.S. NHANES

PubMed Central

Blackwell, Aaron D.; Gurven, Michael D.; Sugiyama, Lawrence S.; Madimenos, Felicia C.; Liebert, Melissa A.; Martin, Melanie A.; Kaplan, Hillard S.; Snodgrass, J. Josh

2011-01-01

Background The peak shift model predicts that the age-profile of a pathogen's prevalence depends upon its transmission rate, peaking earlier in populations with higher transmission and declining as partial immunity is acquired. Helminth infections are associated with increased immunoglobulin E (IgE), which may convey partial immunity and influence the peak shift. Although studies have noted peak shifts in helminths, corresponding peak shifts in total IgE have not been investigated, nor has the age-patterning been carefully examined across populations. We test for differences in the age-patterning of IgE between two South American forager-horticulturalist populations and the United States: the Tsimane of Bolivia (n = 832), the Shuar of Ecuador (n = 289), and the U.S. NHANES (n = 8,336). We then examine the relationship between total IgE and helminth prevalences in the Tsimane. Methodology/Principal Findings Total IgE levels were assessed in serum and dried blood spots and age-patterns examined with non-linear regression models. Tsimane had the highest IgE (geometric mean  = 8,182 IU/ml), followed by Shuar (1,252 IU/ml), and NHANES (52 IU/ml). Consistent with predictions, higher population IgE was associated with steeper increases at early ages and earlier peaks: Tsimane IgE peaked at 7 years, Shuar at 10 years, and NHANES at 17 years. For Tsimane, the age-pattern was compared with fecal helminth prevalences. Overall, 57% had detectable eggs or larva, with hookworm (45.4%) and Ascaris lumbricoides (19.9%) the most prevalent. The peak in total IgE occurred around the peak in A. lumbricoides, which was associated with higher IgE in children <10, but with lower IgE in adolescents. Conclusions The age-patterning suggests a peak shift in total IgE similar to that seen in helminth infections, particularly A. lumbricoides. This age-patterning may have implications for understanding the effects of helminths on other health outcomes, such as allergy, growth

Evidence for a peak shift in a humoral response to helminths: age profiles of IgE in the Shuar of Ecuador, the Tsimane of Bolivia, and the U.S. NHANES.

PubMed

Blackwell, Aaron D; Gurven, Michael D; Sugiyama, Lawrence S; Madimenos, Felicia C; Liebert, Melissa A; Martin, Melanie A; Kaplan, Hillard S; Snodgrass, J Josh

2011-06-01

The peak shift model predicts that the age-profile of a pathogen's prevalence depends upon its transmission rate, peaking earlier in populations with higher transmission and declining as partial immunity is acquired. Helminth infections are associated with increased immunoglobulin E (IgE), which may convey partial immunity and influence the peak shift. Although studies have noted peak shifts in helminths, corresponding peak shifts in total IgE have not been investigated, nor has the age-patterning been carefully examined across populations. We test for differences in the age-patterning of IgE between two South American forager-horticulturalist populations and the United States: the Tsimane of Bolivia (n=832), the Shuar of Ecuador (n=289), and the U.S. NHANES (n=8,336). We then examine the relationship between total IgE and helminth prevalences in the Tsimane. Total IgE levels were assessed in serum and dried blood spots and age-patterns examined with non-linear regression models. Tsimane had the highest IgE (geometric mean =8,182 IU/ml), followed by Shuar (1,252 IU/ml), and NHANES (52 IU/ml). Consistent with predictions, higher population IgE was associated with steeper increases at early ages and earlier peaks: Tsimane IgE peaked at 7 years, Shuar at 10 years, and NHANES at 17 years. For Tsimane, the age-pattern was compared with fecal helminth prevalences. Overall, 57% had detectable eggs or larva, with hookworm (45.4%) and Ascaris lumbricoides (19.9%) the most prevalent. The peak in total IgE occurred around the peak in A. lumbricoides, which was associated with higher IgE in children <10, but with lower IgE in adolescents. The age-patterning suggests a peak shift in total IgE similar to that seen in helminth infections, particularly A. lumbricoides. This age-patterning may have implications for understanding the effects of helminths on other health outcomes, such as allergy, growth, and response to childhood vaccination.

High correlation of specific IgE sensitization between birch pollen, soy and apple allergens indicates pollen-food allergy syndrome among birch pollen allergic patients in northern China.

PubMed

Hao, Guo-Dong; Zheng, Yi-Wu; Wang, Zhi-Xiang; Kong, Xing-Ai; Song, Zhi-Jing; Lai, Xu-Xin; Spangfort, Michael D

2016-05-01

Birch pollen sensitization and associated pollen-food syndrome among Chinese allergic patients have not been investigated. Sera from 203 allergic patients from the northern part of China and collected during February to July 2014 were investigated. Specific immunoglobulin E (IgE) against birch pollen extract Bet v and major birch pollen allergen Bet v 1 were measured using the ADVIA Centaur. The presence of major apple allergen Mal d 1 and soy bean allergen Gly m 4 specific IgE was measured by ImmunoCAP 100. Among the 203 sera, 34 sera (16.7%) had specific IgE to Bet v and of these, 28 sera (82.4%) contained Bet v 1-specific IgE. Among the 28 sera with Bet v 1-specific IgE, 27 sera (96.4%) contained Mal d 1-specific IgE and 22 sera (78.6%) contained Gly m 4-specific IgE. Of the 34 Bet v-positive sera, 6 sera (17.6%) contained no specific IgE for Bet v 1, Mal d 1, or Gly m 4. Almost all Bet v-positive sera were donated during the birch pollen season. The prevalence of birch allergy among patients visiting health care during pollen season can be as high as 16.7% in Tangshan City. The majority of Chinese birch allergic patients are IgE-sensitized to the major birch pollen allergen Bet v 1 as well as to the major apple allergen Mal d 1 and soy bean allergen Gly m 4. A relatively high number of patients (17.6%) are IgE-sensitized to birch pollen allergen(s) other than Bet v 1. The high prevalence of specific IgE to Mal d 1 and Gly m 4 among Bet v 1-sensitized patients indicates that pollen-food allergy syndrome could be of clinical relevance in China.

Effect of active tuberculosis on skin prick allergy tests and serum IgE levels.

PubMed

Kutlu, A; Bozkanat, E; Ciftçi, Fi; Bozkurt, B; Gorur, R; Ardiç, N; Taskapan, O

2008-01-01

Mycobacterium tuberculosis has been shown to suppress allergic airway disease driven by type 2 helper T cells in animal models. In this study, we investigated the effect of active tuberculosis on skin prick test (SPT) positivity and serum immunoglobulin (Ig) E levels of atopic patients with and without tuberculosis infection. Seventeen atopic HIV-negative men with pulmonary tuberculosis and 18 atopic healthy male controls at our military hospital were studied prospectively between March 2005 and March 2006. The sums of all SPT positive tests and positivity to house dust mite alone were calculated before initiation of treatment and after 6 months. Measurement of total serum IgE levels was also performed at the same moments. The mean (SD) initial serum total IgE concentrations were significantly higher in the tuberculosis patients than in the healthy controls (324.1 [317.67] U/mL vs. 146.7 [75.29] U/mL, respectively; P < .05), The total serum IgE concentrations after 6 months of treatment were also higher in the patients than in the controls. The mean sum of SPT positivity was higher in the tuberculosis patients than in the controls at both testing times. Our study does not support the hypothesis that M tuberculosis suppresses atopy and atopic disorders, but large, prospective experimental studies are needed before excluding the possibility of a relationship.

IgE sensitization to Anisakis pegreffii in Italy: Comparison of two methods for the diagnosis of allergic anisakiasis.

PubMed

Mattiucci, S; Colantoni, A; Crisafi, B; Mori-Ubaldini, F; Caponi, L; Fazii, P; Nascetti, G; Bruschi, F

2017-07-01

IgE sensitization to Anisakis pegreffii in Italian subjects suffering from gastro-allergic anisakiasis (GAA) (N=5), or showing chronic urticaria (CU+) after fish consumption (N=100), was investigated. A control group (N=5) was also included. IgE response was analysed by immunoblotting (WB) assay, using both excretory/secretory products (ESPs) and crude extract (CE) of A. pegreffii larvae. The results were compared with those achieved by the conventional immunological method for Anisakis allergy (ie, immunoCAP). Among the 110 subjects, 28 showed IgE positivity with both WB and iCAP methods; 13 proved IgE reactivity, in WB assay, to ESP antigens of A. pegreffii, here provisionally indicated as Ani s 1-like, Ani s 7-like, Ani s 13-like; only 15 sera have shown IgE-WB reaction to Ani s 7-like and Ani s 13-like. iCAP and WB exhibited a high concordance value (κ=1.00) when iCAP value was <0.35 (negative result) and >50.0 (positive result). In the sera samples recorded as positive to Anisakis allergy, Ani s 1-like was responsible for 46.4% of the sensitivity, while Ani s 7-like and Ani s 13-like for 100%. They could be considered as major antigens in the diagnosis of allergic anisakiasis caused by A. pegreffii. © 2017 John Wiley & Sons Ltd.

The Interaction Between Prenatal Exposure to Home Renovation and Reactive Oxygen Species Genes in Cord Blood IgE Response is Modified by Maternal Atopy

PubMed Central

Yu, Jinho; Shin, Youn Ho; Kim, Kyung Won; Suh, Dong In; Yu, Ho-Sung; Kang, Mi-Jin; Lee, Kyung-Shin; Hong, Seo Ah; Choi, Kil Yong; Lee, Eun; Yang, Song-I; Seo, Ju-Hee; Kim, Byoung-Ju; Kim, Hyo-Bin; Lee, So-Yeon; Choi, Suk-Joo; Oh, Soo-Young; Kwon, Ja-Young; Lee, Kyung-Ju; Park, Hee Jin; Lee, Pil Ryang; Won, Hye-Sung

2016-01-01

Purpose Although home renovation exposure during childhood has been identified as a risk factor for the development of allergy, there is limited information on the association between prenatal exposure to home renovation and cord blood (CB) IgE response. The aims of this study were to identify the effect of prenatal exposure to home renovation on CB IgE levels, and to investigate whether this exposure interacts with neonatal genes and whether the effect can be modified by maternal atopy. Methods This study included 1,002 mother-neonate pairs from the COhort for Childhood Origin of Asthma and allergic diseases (COCOA). Prenatal environmental factors were collected using a questionnaire. The levels of CB IgE were measured by the ImmunoCAP system, and DNA was extracted from CB. Results Exposure to home renovation during the prenatal period was associated with significantly higher levels of CB IgE only in neonates from atopic mothers, and the effect of renovation exposure on CB IgE levels persisted from 31 months before birth. Furthermore, prenatal exposure to home renovation increased the risk of CB IgE response interacting with polymorphisms of NRF2 and GSTP1 genes only in neonates from atopic mothers. Conclusions Maternal atopy modified the effect of prenatal exposure to home renovation on CB serum IgE response as well as the interaction between the exposure and neonatal genes involved in the oxidative stress pathway. These findings suggest that the genetically susceptible offspring of atopic mothers may be more vulnerable to the effect of prenatal exposure to home renovation on the development of allergy. PMID:26540500

Positive serum specific IgE has a short half-life in patients with penicillin allergy and reversal does not always indicate tolerance.

PubMed

Hjortlund, Janni; Mortz, Charlotte Gotthard; Stage, Tore Bjerregaard; Skov, Per Stahl; Dahl, Ronald; Bindslev-Jensen, Carsten

2014-01-01

The positive and negative predictive values of specific IgE to penicillins are not well established for penicillin hypersensitivity. One reason may be that serum IgE levels to penicillin diminish over time. The objective in this study was to investigate variations in serum half-life (T½) for specific IgE to penicillins (s-IgE) and to evaluate the outcome of penicillin challenges in patients with previous but not present specific IgE to penicillins. Two subgroups were investigated. All included patients had a history of penicillin allergy with reported symptoms such as urticaria/angioedema or unclassified cutaneous rash. T½ of specific IgE to penicillins was calculated based on sera from 29 patients with repeated measurements of s-IgE. Twenty-two patients with a previous positive s-IgE was followed and challenged with penicillin when IgE had become negative. The T½ for s-IgE varied between the 26 patients with decreasing s-IgE from 1.6 months to 76.4 months and 52% had a T½ of less than a year. The three patients with stable and increasing IgE-values showed T½ approaching infinity A total of 29 challenges with β-lactams were performed. Four different patterns were seen when evaluating the clinical reaction to challenge (positive/negative) and post-challenge boost of s-IgE (yes/no). Eight (36.4%) had negative challenge and negative post-challenge s-IgE, eight (36.4%) negative challenge, but positive post-challenge s-IgE levels. 3 (13.6%) had positive challenge and positive post-challenge s-IgE whereas 3 (13.6%) were challenge positive, but had negative post-challenge s-IgE. Specific IgE to penicillins declines over time stressing the importance of a close time relation between diagnostic work-up and clinical reaction. Reversal of previously positive s-IgE may still be associated with positive penicillin challenges and/or re-boostering of s-IgE to positivity.

Effect of industrial processing on the IgE reactivity of three commonly consumed Mo-roccan fish species in Fez region.

PubMed

Mejrhit, N; Azdad, O; Aarab, L

2018-03-02

Objectives. The aim of this work was to study the effect of industrial processing on the allergenicity of three commonly consumed Moroccan fish species in Fez region (sardine, common pandora, and shrimp). Methods. This work was conducted by a sera-bank obtained from 1248 patients recruited from Fez Hospitals. Their sera were analyzed for specific IgE binding to raw fish extracts. Among them, 60 patients with higher specific IgE levels were selected, and used to estimate the binding variation of IgE to these products under several processing (frying, cooking, canning, marinade, and fermentation) using ELISA analysis. Results. ELISA results demonstrated that all the studied processing cause a reduction in the immunoreactivity of human IgE to fish products, with a high action with marinade and fermentation compared to other processing. This alteration was also observed with rabbit IgG in all processed products, showing that the maximum reduction was marked in fermented sardine with 64.5%, in cooked common pandora with 58%, and in fermented shrimp with 69.2%. Conclusion. In conclusion, our study has shown that the allergenicity of the three studied fish could be reduced by different industrial processes with different degrees.

Prevalence of IgE antibodies to grain and grain dust in grain elevator workers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lewis, D.M.; Romeo, P.A.; Olenchock, S.A.

1986-04-01

IgE-mediated allergic reactions have been postulated to contribute to respiratory reactions seen in workers exposed to grain dusts. In an attempt better to define the prevalence of IgE antibodies in workers exposed to grain dusts, we performed the radioallergosorbent test (RAST) on worker sera using both commercial allergens prepared from grain and worksite allergens prepared from grain dust samples collected at the worksite. We found that the two types of reagents identified different populations with respect to the specificity of IgE antibodies present. The RAST assay performed using worksite allergens correlated well with skin test procedures. These results may allowmore » us to gain better understanding of allergy associated with grain dust exposure, and document the utility of the RAST assay in assessment of occupational allergies.« less

Prevalence of IgE antibodies to grain and grain dust in grain elevator workers.

PubMed Central

Lewis, D M; Romeo, P A; Olenchock, S A

1986-01-01

IgE-mediated allergic reactions have been postulated to contribute to respiratory reactions seen in workers exposed to grain dusts. In an attempt better to define the prevalence of IgE antibodies in workers exposed to grain dusts, we performed the radioallergosorbent test (RAST) on worker sera using both commercial allergens prepared from grain and worksite allergens prepared from grain dust samples collected at the worksite. We found that the two types of reagents identified different populations with respect to the specificity of IgE antibodies present. The RAST assay performed using worksite allergens correlated well with skin test procedures. These results may allow us to gain better understanding of allergy associated with grain dust exposure, and document the utility of the RAST assay in assessment of occupational allergies. PMID:3709478

Serum IgE and IgG responses to food antigens in normal and atopic dogs, and dogs with gastrointestinal disease.

PubMed

Foster, A P; Knowles, T G; Moore, A Hotston; Cousins, P D G; Day, M J; Hall, E J

2003-05-12

In human food allergy, with or without concurrent atopy, there may be significant increases in serum allergen-specific IgE. Serological methods have been tried but are not currently recommended for diagnosis of suspected food allergy in dogs. The aim of this study was to investigate humoral immune responses to food antigens in dogs. Serum IgG and IgE antibodies specific for food antigens were measured by enzyme linked immunosorbent assay (ELISA) using polyclonal anti-dog IgG and IgE reagents. Antigens tested were beef, chicken, pork, lamb, chicken, turkey, white fish, whole egg, wheat, soybean, barley, rice, maize corn, potato, yeast and cow's milk. Three groups were examined: normal dogs, dogs with atopic dermatitis (AD); and dogs with one of four types of gastrointestinal (GI) disease: small intestinal bacterial overgrowth (SIBO), inflammatory bowel disease (IBD), food-responsive disease, and infectious diarrhoea. Statistically significant differences in food-specific antibodies were not detected between the GI subgroups. There were statistically significant differences in the IgE concentration between the normal dogs, and dogs with atopic or GI disease, for all of the antigens tested. There were statistically significant differences in the average IgG concentrations between the normal dogs, and dogs with atopic or GI disease, for all of the antigens tested, except egg and yeast. The relationship of antigen responses for pooled data was analysed using principle component analysis and cluster plots. Some clustering of variables was apparent for both IgE and IgG. For example, all dogs (normal and diseased) made a similar IgG antibody response to chicken and turkey. Compared with other groups, atopic dogs had more food allergen-specific IgE and this would be consistent with a Th(2) humoral response to food antigens. Dogs with GI disease had more food allergen-specific IgG compared with the other groups. This may reflect increased antigen exposure due to increased

Novel IgE Inhibitors for the Treatment of Food Allergies

DTIC Science & Technology

2015-10-01

currently the only FDA approved monoclonal anti-IgE therapy. We solved the IgE:omalizumab crystal structure to 2.54 Å. This structure elucidates the...Surprisingly, the complex structure shares significant similarity with the disruptive IgE inhibitor E2_79, and provides mechanistic insight into the...efficiency with which disruptive inhibitors are able to bind to, and accelerate FcεRIα dissociation from preformed IgE:FcεRIα complexes. Structural

IgE recognition of chimeric isoforms of the honeybee (Apis mellifera) venom allergen Api m 10 evaluated by protein array technology.

PubMed

Van Vaerenbergh, Matthias; De Smet, Lina; Rafei-Shamsabadi, David; Blank, Simon; Spillner, Edzard; Ebo, Didier G; Devreese, Bart; Jakob, Thilo; de Graaf, Dirk C

2015-02-01

Api m 10 has recently been established as novel major allergen that is recognized by more than 60% of honeybee venom (HBV) allergic patients. Previous studies suggest Api m 10 protein heterogeneity which may have implications for diagnosis and immunotherapy of HBV allergy. In the present study, RT-PCR revealed the expression of at least nine additional Api m 10 transcript isoforms by the venom glands. Two distinct mechanisms are responsible for the generation of these isoforms: while the previously known variant 2 is produced by an alternative splicing event, novel identified isoforms are intragenic chimeric transcripts. To the best of our knowledge, this is the first report of the identification of chimeric transcripts generated by the honeybee. By a retrospective proteomic analysis we found evidence for the presence of several of these isoforms in the venom proteome. Additionally, we analyzed IgE reactivity to different isoforms by protein array technology using sera from HBV allergic patients, which revealed that IgE recognition of Api m 10 is both isoform- and patient-specific. While it was previously demonstrated that the majority of HBV allergic patients display IgE reactivity to variant 2, our study also shows that some patients lacking IgE antibodies for variant 2 display IgE reactivity to two of the novel identified Api m 10 variants, i.e. variants 3 and 4. Copyright © 2014 Elsevier Ltd. All rights reserved.

Treatment of cashew extracts with Aspergillopepsin reduces IgE binding to cashew allergens

USDA-ARS?s Scientific Manuscript database

Cashew nuts can cause serious and sometimes life threatening reactions in people that suffer from food allergies. These reactions are mediated by immunoglobulin E binding (IgE) to allergenic cashew proteins. Enzymes from Aspergillus fungal species are used in many industrial and pharmaceutical appli...

Structural characterization and IgE epitope analysis of arginine kinase from Scylla paramamosain

USDA-ARS?s Scientific Manuscript database

Arginine kinase (AK) has been reported as the pan-allergen of shellfish, however, there is limited information about its IgE epitopes and structural characteristics. In this study, AK from Scylla paramamosain was purified and characterized. The purified AK was a glycoprotein with the molecular weigh...

The effect of three-monthly albendazole treatment on Th2 responses: Differential effects on IgE and IL-5.

PubMed

de Ruiter, K; Tahapary, D L; Wammes, L J; Wiria, A E; Hamid, F; van Lieshout, L; Smit, J W A; Houwing-Duistermaat, J J; Sartono, E; Supali, T; Yazdanbakhsh, M

2017-06-01

Helminth parasites induce a strong Th2 response, characterized by high levels of IgE and elevated signature cytokines such as IL-5. As many global deworming programmes are underway, there is concern that this might lead to emergence of Th1-mediated pathologies when the counterbalancing helminth-induced Th2 response is absent. Therefore, we assessed the effect of deworming on Th2-mediated responses in a household-clustered randomized controlled trial in Indonesia. Total plasma IgE and whole-blood IL-5 responses to mitogen phytohaemagglutinin (PHA) were measured in 1494 and 682 subjects, respectively, at baseline, 9 and 21 months after three-monthly single-dose treatment with albendazole or placebo. Anthelmintic treatment did not result in complete removal of helminth infections in the community. However, treatment significantly decreased IgE levels in albendazole- compared to placebo-treated subjects. IL-5 responses to PHA were not significantly affected by anthelmintic treatment and tended to increase in albendazole-treated subjects, indicating that intensive treatment of helminth parasites has different outcomes on B-cell (IgE levels) and T-cell (IL-5) responses. The data shows that 2 years of deworming can have differential effects on responses typified as Th2-mediated, which needs to be taken into account when examining the impact of helminths on noncommunicable diseases. © 2017 John Wiley & Sons Ltd.

T-helper 17-related cytokines and IgE antibodies during hepatitis A virus infection in children.

PubMed

Trujillo-Ochoa, Jorge L; Corral-Jara, Karla F; Escobedo-Meléndez, Griselda; Realpe, Mauricio; Panduro, Arturo; Roman, Sonia; Fierro, Nora A

2015-04-01

We determined the serum IgE levels and T-helper (Th)17-related cytokines during distinct hepatitis A virus (HAV)-induced clinical courses in children. A significantly higher concentration of macrophage inflammatory protein 3α, interleukin (IL)-17E and IL-17F in HAV-infected children with intermediate liver injury compared with those with minor liver damage was found. A reduction in the IgE levels in those patients who showed the highest levels of IL-17F in the group of intermediate liver injury was found. The data suggested that the Th17-related profile is associated with the severity of HAV infection and might play a role on the modulation achieved by HAV during allergies.

Effects of routine prophylactic vaccination or administration of aluminum adjuvant alone on allergen-specific serum IgE and IgG responses in allergic dogs.

PubMed

Tater, Kathy C; Jackson, Hilary A; Paps, Judy; Hammerberg, Bruce

2005-09-01

To determine the acute corn-specific serum IgE and IgG, total serum IgE, and clinical responses to s.c. administration of prophylactic vaccines and aluminum adjuvant in corn-allergic dogs. 20 allergic and 8 nonallergic dogs. 17 corn-allergic dogs were vaccinated. Eight clinically normal dogs also were vaccinated as a control group. Serum corn-specific IgE, corn-specific IgG, and total IgE concentrations were measured in each dog before vaccination and 1 and 3 weeks after vaccination by use of an ELISA. The corn-allergic dogs also had serum immunoglobulin concentrations measured at 8 and 9 weeks after vaccination. Twenty allergic dogs received a s.c. injection of aluminum adjuvant, and serum immunoglobulin concentrations were measured in each dog 1, 2, 3, 4, and 8 weeks after injection. The allergic dogs were examined during the 8 weeks after aluminum administration for clinical signs of allergic disease. The allergic dogs had significant increases in serum corn-specific IgE and IgG concentrations 1 and 3 weeks after vaccination but not 8 or 9 weeks after vaccination. Control dogs did not have a significant change in serum immunoglobulin concentrations after vaccination. After injection of aluminum adjuvant, the allergic dogs did not have a significant change in serum immunoglobulin concentrations or clinical signs. Allergen-specific IgE and IgG concentrations increase after prophylactic vaccination in allergic dogs but not in clinically normal dogs. Prophylactic vaccination of dogs with food allergies may affect results of serologic allergen-specific immunoglobulin testing performed within 8 weeks after vaccination.

Effect of tyrosinase-aided crosslinking on the IgE binding potential and conformational structure of shrimp (Metapenaeus ensis) tropomyosin.

PubMed

Ahmed, Ishfaq; Lv, Liangtao; Lin, Hong; Li, Zhenxing; Ma, Jiaju; Guanzhi, Chen; Sun, Lirui; Xu, Lili

2018-05-15

The present study was performed to determine crosslinking and oxidative reactions catalyzed by tyrosinase (Tyr), caffeic acid (CA) and their combination with respect to IgE binding potential and conformational structure of shrimp tropomyosin (TM). Cross-links and IgE binding potentials were analyzed by SDS-PAGE, western blot and indirect ELISA. While structural changes were characterized using surface hydrophobicity, ultraviolet (UV), fluorescence and circular dichroism (CD) spectroscopies. Maximum reduction in the IgG (37.19%) and IgE binding potentials (49.41%) were observed when treated with 2000 nkat/g Tyr + CA, as indicated by ELISA analyses. These findings correlated well with the denaturation of protein, as evident by slight blue shift and alterations in the ellipticities observed via structural analyses. The results demonstrated that addition of CA mediator with Tyr pronouncedly enhanced crosslinking, and altered the conformational structure, thereby mitigated allergenicity of TM, thus showing promise in developing novel food structures with reduced allergenic potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessment of IgE binding to native and hydrolyzed soy protein in serum obtained from dogs with experimentally induced soy protein hypersensitivity.

PubMed

Serra, Montserrat; Brazís, Pilar; Fondati, Alessandra; Puigdemont, Anna

2006-11-01

To assess binding of IgE to native, whole hydrolyzed, and separated hydrolyzed fractions of soy protein in serum obtained from dogs with experimentally induced soy protein hypersensitivity. 8 naïve Beagles (6 experimentally sensitized to native soy protein and 2 control dogs). 6 dogs were sensitized against soy protein by administration of allergens during a 90-day period. After the sensitization protocol was completed, serum concentrations of soy-specific IgE were measured and intradermal skin tests were performed in all 6 dogs to confirm that the dogs were sensitized against soy protein. Serum samples from each sensitized and control dog underwent western blot analysis to assess the molecular mass band pattern of the different allergenic soy fractions and evaluate reactivities to native and hydrolyzed soy protein. In sera from sensitized dogs, a characteristic band pattern with 2 major bands (approx 75 and 50 kd) and 2 minor bands (approx 31 and 20 kd) was detected, whereas only a diffuse band pattern associated with whole hydrolyzed soy protein was detected in the most reactive dog. Reactivity was evident only for the higher molecular mass peptide fraction. In control dogs, no IgE reaction to native or hydrolyzed soy protein was detected. Data suggest that the binding of soy-specific IgE to the hydrolyzed soy protein used in the study was significantly reduced, compared with binding of soy-specific IgE to the native soy protein, in dogs with experimentally induced soy hypersensitivity.

Detection of ovomucoid-specific low-affinity IgE in infants and its relationship to eczema.

PubMed

Kawamoto, Norio; Kamemura, Norio; Kido, Hiroshi; Fukao, Toshiyuki

2017-06-01

Allergen-specific low-affinity IgE was previously detected in cord blood by a highly sensitive densely carboxylated protein (DCP) chip, but not by ImmunoCAP. Here, we investigated the presence of low-affinity IgE during the early life of infants and observed its relationship with eczema. We conducted a birth cohort study, collecting sera at birth and 6 and 14 months of age (n = 110). We monitored the ovomucoid (OM)- and egg white (EW)-specific IgE (sIgE) by ImmunoCAP or DCP chip and analyzed the antigen affinity of sIgE by binding inhibition assays in the presence or absence of a mild chaotropic agent, diethyl amine (DEA). The low- and high-affinity OM-sIgEs and sensitization risk factors were analyzed by a multivariate logistic analysis. The OM-sIgE measured by DCP chip significantly correlated with that measured by ImmunoCAP, but some samples assessed as OM-sIgE positive by DCP chip were considered OM-sIgE negative by ImmunoCAP. Binding inhibition analysis after DEA treatment was performed for participants judged as OM-sIgE positive by DCP chip at 14 M. The group assessed as negative for OM- and EW-sIgE by ImmunoCAP at 6 and 14 months showed a larger binding inhibition curve shift after DEA treatment than did the group assessed as positive at these times, indicating the presence of low-affinity sIgE antibodies at 14 months. The logistic regression analysis found that persistent eczema from 6 to 14 months is a significant risk factor for developing high-affinity, but not low-affinity, sIgE. Human infant peripheral blood contains allergen-specific low-affinity sIgE. Persistent eczema is related to the development of high-affinity, but not low-affinity, IgE. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Identification of Aspergillus (A. flavus and A. niger) Allergens and Heterogeneity of Allergic Patients' IgE Response.

PubMed

Vermani, Maansi; Vijayan, Vannan Kandi; Agarwal, Mahendra Kumar

2015-08-01

Aspergillus species (A. flavus and A. niger) are important sources of inhalant allergens. Current diagnostic modalities employ crude Aspergillus extracts which only indicate the source to which the patient has been sensitized, without identifying the number and type of allergens in crude extracts. We report a study on the identification of major and minor allergens of the two common airborne Aspergillus species and heterogeneity of patients' IgE response to them. Skin prick tests were performed on 300 patients of bronchial asthma and/or allergic rhinitis and 20 healthy volunteers. Allergen specific IgE in patients' sera was estimated by enzyme allergosorbent test (EAST). Immunoblots were performed to identify major/minor allergens of Aspergillus extracts and to study heterogeneity of patients'IgE response to them. Positive cutaneous responses were observed in 17% and 14.7% of patients with A. flavus and A. niger extracts, respectively. Corresponding EAST positivity was 69.2% and 68.7%. In immunoblots, 5 allergenic proteins were identified in A. niger extract, major allergens being 49, 55.4 and 81.5 kDa. Twelve proteins bound patients' IgE in A. flavus extract, three being major allergens (13.3, 34 and 37 kDa). The position and slopes of EAST binding and inhibition curves obtained with individual sera varied from patient to patient. The number and molecular weight of IgE-binding proteins in both the Aspergillus extracts varied among patients. These results gave evidence of heterogeneity of patients' IgE response to major/minor Aspergillus allergens. This approach will be helpful to identify disease eliciting molecules in the individual patients (component resolved diagnosis) and may improve allergen-specific immunotherapy.

Food allergen-specific serum IgG and IgE before and after elimination diets in allergic dogs.

PubMed

Zimmer, Anja; Bexley, Jennifer; Halliwell, Richard E W; Mueller, Ralf S

2011-12-15

Serum food allergen-specific antibody testing is widely offered to identify suitable ingredients for diets to diagnose adverse food reaction (AFR) in dogs with allergic skin disease. Antibody concentrations in blood samples obtained during an unsuccessful diet to help in the choice of diet changes may be influenced by the previous diet. The objective of this paper was to measure food antigen-specific IgE and IgG for the most commonly used 16 food antigens before and after an elimination diet. Levels of food-specific serum IgE and IgG antibodies were measured by enzyme-linked immunosorbent assay (ELISA). Dogs had detectable IgE antibodies to beef, pork, lamb and cows' milk; and detectable IgG antibodies to beef, pork, lamb, cows' milk, chicken and turkey. Of 19 dogs with complete data sets, 14 dogs showed clear improvement during diet and in 7 dogs AFR could be diagnosed by deterioration on rechallenge and subsequent improvement on refeeding the diet. Serum was obtained before and 6-8 weeks after beginning such a diet. There was no significant difference in pre- and post-diet levels for any of the individual allergens nor for the total IgE and IgG concentrations of all antigens (P=0.55 and P=0.53 respectively). In these 19 dogs in which an elimination diet was used for the diagnosis of food allergy and in which 14 were probably food allergic and 7 were proven food allergic there were no significant differences in food-specific antibodies before and after an elimination diet of 6-8 weeks. Copyright © 2011 Elsevier B.V. All rights reserved.

Characterization of histamine-releasing activity: role of cytokines and IgE heterogeneity.

PubMed

Liao, T N; Hsieh, K H

1992-07-01

Histamine-releasing factors (HRFs) are a group of cytokines that cause histamine release (HR) from basophils and mast cells. The concept of the priming effect of cytokines and the heterogeneity of IgE involved in the HRF-induced HR have been emphasized in recent years. In this study, we performed a series of experiments to elucidate the above-mentioned hypotheses. The stock HRF were obtained by stimulating mononuclear cells (MNC) with phytohemagglutinin (PHA). Maximal activity was observed 36 hr after culture. By gel filtration, HRF was eluted with a peak activity ranging from 12 to 18 KD. A large portion (75%) of HRF activity could be neutralized by a combination of antibodies against interleukin 1 (IL-1), IL-3, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha). The stimulation of basophils with 100 ng/ml each of IL-3, IL-6, IL-7, GM-CSF, or TNF-alpha alone caused 10% HR; however, when the cells were pretreated with 10 ng/ml of either IL-3, IL-6, IL-7, IL-8, TNF-alpha, or GM-CSF and then stimulated with anti-IgE, a marked increase in HR was regularly observed. The combination of 100 ng/ml each of IL-1, IL-3, IL-8, GM-CSF, and TNF-alpha could induce only about 20% HR; furthermore, such combinations did not have an additive or synergistic priming effect on anti-IgE-induced HR compared to the effect of single cytokines. Stripping of surface-bound IgE with lactic acid markedly reduced the capacity of basophils to release histamine in response to MNC-HRF and anti-IgE. Passive sensitization of IgE-stripped basophils with high-HRF responders' serum could restore their responsiveness to both MNC-HRF and anti-IgE, but passive sensitization with low-HRF responders' serum could restore responsiveness to anti-IgE only. Moreover, passage of MNC-HRF through high-, but not low-HRF, responders' IgE-Sepharose columns significantly reduced the HR activity of MNC-HRF. Finally, although the eluant could induce only 10% HR

[Recognition of excretory/secretory antigens of Anisakis type I and evolution of IgE in experimentally infected rats].

PubMed

Gómez-Mateos, Magdalena; Valero-López, Adela; de la Rubia-Nieto, Teresa; Romero-López, María Del Carmen; Díaz-Sáez, Victoriano

2014-10-01

Anisakis spp., during parasitism, release excretory-secretory antigens that, in contact with the human immune system, can trigger a hypersensitivity response mediated by IgE, causing various allergic symptoms. To evaluate the IgE response in Wistar rats after infection with L3 larvae of the parasite Anisakis spp. Some determining factors involved in the technique have been improved in this work, such as: the concentration of polyacrylamide used in the preparation of the gels, the antigen concentration used, and the temperature required for denaturation of proteins. Immune responses (Ag-Ab) observed by the immunoblotting technique showed a greater intensity with serum obtained after reinfection, which have recognized proteins that may correspond to the major antigen Ani s 1 and other polypeptides of interest in the diagnosis of human anisakiasis. This paper concludes that immunoblotting is a useful technique to detect IgE antibodies against Anisakis proteins. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Identification of IgE- binding pollen protein from Cannabis sativa in pollen-hypersensitive patients from north Pakistan.

PubMed

Choudhary, Shazia; Murad, Sheeba; Hayat, Muhammad Qasim; Shakoor, Zahid; Arshad, Muhammad

2017-01-01

Cannabis sativa (C.sativa) is well-known for its medicinal, industrial and recreational use. However, allergies in relation to Cannabis sativa (C.sativa) are rarely reported. C. sativa is one of the common weeds found in Pakistan and its pollen grains are common in spring and fall season. Although categorized as an aeroallergen, there are limited number of reports regarding allergenic potential in C. sativa. Therefore, the current study is aimed at exploring the IgE- binding potential among the C. sativa pollen in local pollen allergic patients. Initial screening of C. sativa sensitized individuals was carried out by dot blot from the sera of pollen allergic patients. Proteins from the pollen grains were extracted and resolved on 10% gel. Eight bands were visible on gel however only one protein fragment i.e. of 14KDa size was found to bind to IgE as analyzed through protein gel blot analysis. Strong IgE affinity of a 14 kDa protein fragment from C. sativa pollen extract suggests its allergenic potential. Further study is required to find the exact nature of this protein fragment.

High frequency of IgE sensitization towards kiwi seed storage proteins among peanut allergic individuals also reporting allergy to kiwi.

PubMed

van Odijk, Jenny; Sjölander, Sigrid; Brostedt, Peter; Borres, Magnus P; Englund, Hillevi

2017-01-01

IgE sensitization to storage proteins from nuts and seed is often related to severe allergic symptoms. There is a risk of immunological IgE cross-reactivity between storage proteins from different species. The potential clinical implication of such cross-reactivity is that allergens other than the known sensitizer can cause allergic symptoms. Previous studies have suggested that kiwi seed storage proteins may constitute hidden food allergens causing cross-reactive IgE-binding with peanut and other tree nut homologs, thereby mediating a potential risk of causing allergy symptoms among peanut ant tree nut allergic individuals. The objective of this study was to investigate the degree of sensitization towards kiwi fruit seed storage proteins in a cohort of peanut allergic individuals. A cohort of 59 adolescents and adults with peanut allergy was studied, and self reported allergies to a number of additional foods were collected. Quantitative IgE measurements to seed storage proteins from kiwi and peanut were performed. In the cohort, 23 out of the 59 individuals were reporting kiwi fruit allergy (39%). The frequency of IgE sensitization to kiwi fruit and to any kiwi seed storage protein was higher among peanut allergic individuals also reporting kiwi fruit allergy ( P  = 0.0001 and P  = 0.01). A positive relationship was found between IgE levels to 11S globulin (r = 0.65) and 7S globulin (r = 0.48) allergens from kiwi and peanut, but IgE levels to 2S albumin homologs did not correlate. Patients reporting kiwi fruit allergy also reported allergy to hazelnut ( P  = 0.015), soy ( P  < 0.0001), pea ( P  = 0.0002) and almond ( P  = 0.016) to a higher extent than peanut allergic individuals without kiwi allergy. Thirty-nine percent of the peanut allergic patients in this cohort also reported kiwi fruit allergy, they displayed a higher degree of sensitization to kiwi storage proteins from both kiwi and peanut, and they also reported a higher extent of allergy

Detection of specific IgE antibodies to major and minor antigenic determinants in sera of penicillin allergic patients.

PubMed

Zhao, Yongxing; Qiao, Hailing

2003-12-01

To investigate the mechanism(s) of penicillins allergic reaction. The radioallergosorbent test (RAST) was used to detect 9 specific IgE antibodies, including major antigenic determinants: benzylpenicilloyl (BPO), ampicilloyl (APO), amoxicilloyl (AXO), phenoxomethylpenicilloyl (PVO) and flucloxacilloyl (FLUO), and minor antigenic determinants: benzylpenicillanyl (BPA), amoxicillanyl (AXA), 6-aminopenicillanic (APA) and phenoxomethylpenicillany (PVA), in the sera of 32 penicillin allergic patients. The relationship between specific IgE antibodies and penicillins chemical structures was studied by radioallergosorbent inhibition test. Nineteen of 32 patients (59.4%) were RAST positive, among whom, five cases were positive only to one or two antigenic minor determinants, and three cases were positive only to one or three major antigenic determinants. The remaining 11 patients were positive not only to major antigenic determinants but also minor antigenic determinants. In 9 specific IgE antibodies, the positive rate of PVA-IgE was the highest (34.38%), followed by BPO-IgE (31.25%). The positive rate of FLUO-IgE was the lowest (15.63%). Of the total patient group, 53.13% were positive to one or more minor antigenic determinants, while 37.5% (12/32) were positive to one or more major antigenic determinants. The percentage of patients with urticarial reactions who were positive to minor antigenic determinants (63.16%) was significantly higher than observed in the anaphylactic shock group (38.5%, P < 0.05). The minor antigenic determinant was important in allergic reaction. The combining sites of the specific IgE antibodies were likely to be the side-chain of drug or the overwhelming drug molecule.

Agreement between allergen-specific IgE assays and ensuing immunotherapy recommendations from four commercial laboratories in the USA

PubMed Central

Plant, Jon D; Neradelik, Moni B; Polissar, Nayak L; Fadok, Valerie A; Scott, Brian A

2014-01-01

Background Canine allergen-specific IgE assays in the USA are not subjected to an independent laboratory reliability monitoring programme. Hypothesis/Objectives The aim of this study was to evaluate the agreement of diagnostic results and treatment recommendations of four serum IgE assays commercially available in the USA. Methods Replicate serum samples from 10 atopic dogs were submitted to each of four laboratories for allergen-specific IgE assays (ACTT®, VARL Liquid Gold, ALLERCEPT® and Greer® Aller-g-complete®). The interlaboratory agreement of standard, regional panels and ensuing treatment recommendations were analysed with the kappa statistic (κ) to account for agreement that might occur merely by chance. Six comparisons of pairs of laboratories and overall agreement among laboratories were analysed for ungrouped allergens (as tested) and also with allergens grouped according to reported cross-reactivity and taxonomy. Results The overall chance-corrected agreement of the positive/negative test results for ungrouped and grouped allergens was slight (κ = 0.14 and 0.13, respectively). Subset analysis of the laboratory pair with the highest level of diagnostic agreement (κ = 0.36) found slight agreement (κ = 0.13) for ungrouped plants and fungi, but substantial agreement (κ = 0.71) for ungrouped mites. The overall agreement of the treatment recommendations was slight (κ = 0.11). Altogether, 85.1% of ungrouped allergen treatment recommendations were unique to one laboratory or another. Conclusions and clinical importance Our study indicated that the choice of IgE assay may have a major influence on the positive/negative results and ensuing treatment recommendations. PMID:24461034

Detection of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens

PubMed Central

Vojdani, Aristo

2009-01-01

Background Despite the first documented case of food allergy to cooked food in 1921 by Prausnitz and Kustner, all commercial food antigens are prepared from raw food. Furthermore, all IgE and IgG antibodies against dietary proteins offered by many clinical laboratories are measured against raw food antigens. Methods We developed an enzyme-linked immunosorbent assay for the measurement of IgE, IgG, IgA and IgM antibodies against raw and processed food antigens. Sera with low or high reactivity to modified food antigens were subjected to myelin basic protein, oxidized low density lipoprotein, and advanced glycation end products (AGE) such as AGE-human serum albumin and AGE-hemoglobin. Results Compared to raw food antigens, IgE antibodies showed a 3–8-fold increase against processed food antigens in 31% of the patients. Similarly, IgG, IgA and IgM antibodies against modified food antigens overall were found at much higher levels than antibody reactions against raw food antigens. Almost every tested serum with high levels of antibodies against modified food antigens showed very high levels of antibodies against myelin basic protein, oxidized low density lipoprotein, AGE-human serum albumin and AGE-hemoglobin. Conclusion We conclude that the determination of food allergy, intolerance and sensitivity would be improved by testing IgE, IgG, IgA and IgM antibodies against both raw and processed food antigens. Antibodies against modified food antigens, by reacting with AGEs and tissue proteins, may cause perturbation in degenerative and autoimmune diseases such as diabetes, atherosclerosis, inflammation, autoimmunity, neurodegeneration and neuroautoimmunity. PMID:19435515

Heterogeneity of the IgE response to allergenic determinants of cefaclor in serum samples from patients with cefaclor-induced anaphylaxis.

PubMed

Kim, Sang-Hoon; Choi, Jeong-Hee; Park, Hae-Sim

2005-06-01

Beta-lactam antibiotics, such as cefaclor, may cause IgE-mediated anaphylactic reactions. However, the clinically available serologic test has not been widely accepted, and the antigenic determinants of these drugs are unclear. To describe 4 cases of anaphylaxis caused by cefaclor in which a specific IgE response to cefaclor was demonstrated. Four patients with anaphylaxis to cefaclor and 35 nonatopic controls never exposed to cefaclor were studied. Skin tests and oral challenges with this drug were performed. The specific IgE response to the antigenic determinant of cefaclor-human serum albumin (HSA) conjugate was compared in each patient. The serum specific IgE to cefaclor-HSA conjugate was detected using enzyme-linked immunosorbent assay (ELISA). Also, ELISA inhibition studies using various concentrations of cefaclor-HSA, HSA alone, and free cefaclor were performed, as were hapten inhibition studies using cefaclor, cephalexin, cefadroxil, ampicillin, ceftriaxone, and cefotaxime. Three patients showed high levels of serum specific IgE to cefaclor-HSA and marked inhibition patterns to free cefaclor and cefaclor-HSA conjugate on ELISA inhibition testing. Hapten inhibition testing in 3 individual serum samples showed 2 different patterns. In patient 3, significant dose-dependent inhibitions (up to 92%) were noted with additions of free cefaclor and cefaclor-HSA conjugate, and lesser inhibitions (up to 74%) were noted with cephalexin, which shares the aminobenzyl side chain. In patients 1 and 2, marked dose-dependent inhibitions were noted only with additions of cefaclor-HSA conjugate and free cefaclor, whereas minimal inhibitions were noted with the other 5 compounds. The specific IgE response to cefaclor-HSA conjugate in patients with cefaclor anaphylaxis occurs against the hapten, in which heterogeneity of the antigenic determinant was noted to depend on the individual.

What are the main environmental exposures associated with elevated IgE in Cuban infants? A population-based study

PubMed Central

Fundora-Hernández, Hermes; Venero-Fernández, Silvia J; Suárez-Medina, Ramón; Mora-Faife, Esperanza de la C; García-García, Gladys; del Valle-Infante, Ileana; Gómez-Marrero, Liem; Venn, Andrea; Britton, John; Fogarty, Andrew W

2014-01-01

Objective Immunoglobulin E (IgE) plays a key role in allergy disease pathogenesis, but little is known about the environmental factors associated with higher IgE levels in infants. The aim of this study was to determine the risk factors for elevated serum total IgE infants living in Havana. Methods Eight hundred and seventy-seven infants provided blood samples. Data on allergic disease symptoms and a wide range of exposures were collected. Results The median IgE was 35IU/ml (interquartile range 13–96). The risk of having an IgE level above the median was higher for children who had been breastfed for 4 months or more (adjusted odds ratio (OR) 1.28; 95% confidence interval (CI): 1.02–1.61) and for children who reported cockroaches in their home (OR 1.30; 95% CI: 1.03–1.63). The risk was lower for children whose mother was in paid employment (OR 0.73; 95% CI: 0.54–0.97 compared with those who did not), for children living in homes where gas and electricity were used for cooking (OR 0.45; 95% CI: 0.32–0.62 compared with electricity only) and for children with domestic pets at birth (OR 0.83; 95% CI: 0.70-1.00). There was no association between paracetamol use and serum IgE levels. Conclusions Associations between gas fuel use and maternal employment indicate that IgE levels in early life are lower in children who may be living in relative affluence. The discrepancy in the effect of early exposure to pets or cockroaches may reflect differences in these allergens, or be confounded by relative affluence. Further investigation of this cohort will determine how these effects translate into the expression of allergic disease in later life. Objectif Les immunoglobulines E (IgE) jouent un rôle clé dans la pathogenèse de la maladie allergique, mais on sait peu sur les facteurs environnementaux associés à des taux plus élevés d'IgE chez les nourrissons. Le but de cette étude était de déterminer les facteurs de risque pour un taux élevé d'IgE s

IFN-gamma-mediated inhibition of human IgE synthesis by IL-21 is associated with a polymorphism in the IL-21R gene.

PubMed

Pène, Jérôme; Guglielmi, Laurence; Gauchat, Jean-François; Harrer, Nathalie; Woisetschläger, Maximilian; Boulay, Vera; Fabre, Jean-Michel; Demoly, Pascal; Yssel, Hans

2006-10-15

IL-21 is a cytokine produced by CD4+ T cells that has been reported to regulate human, as well as, mouse T and NK cell function and to inhibit Ag-induced IgE production by mouse B cells. In the present study, we show that human rIL-21 strongly enhances IgE production by both CD19+ CD27- naive, and CD19+ CD27+ memory B cells, stimulated with anti-CD40 mAb and rIL-4 and that it promotes the proliferative responses of these cells. However, rIL-21 does not significantly affect anti-CD40 mAb and rIL-4-induced Cepsilon promoter activation in a gene reporter assay, nor germline Cepsilon mRNA expression in purified human spleen or peripheral blood B cells. In contrast, rIL-21 inhibits rIL-4-induced IgE production in cultures of PBMC or total splenocytes by an IFN-gamma-dependent mechanism. The presence of a polymorphism (T-83C), in donors heterozygous for this mutation was found to be associated not only with lower rIL-21-induced IFN-gamma production levels, but also with a lower sensitivity to the inhibitory effects of IL-21 on the production of IgE, compared with those in donors expressing the wild-type IL-21R. Taken together, these results show that IL-21 differentially regulates IL-4-induced human IgE production, via its growth- and differentiation-promoting capacities on isotype-, including IgE-, committed B cells, as well as via its ability to induce IFN-gamma production, most likely by T and NK cells, whereas the outcome of these IL-21-mediated effects is dependent on the presence of a polymorphism in the IL-21R.

High IgE sensitization to maize and rice pollen in the highlands of Madagascar

PubMed Central

Ramavovololona; Sénéchal, Hélène; Andrianarisoa, Ange; Rakotoarimanana, Vololona; Godfrin, Dominique; Peltre, Gabriel; Poncet, Pascal; Sutra, Jean-Pierre

2014-01-01

Introduction Maize and rice are two crops constituting the main food supply in many under-developed and developing countries. Despite the large area devoted to the culture, the sensitization to the pollen from these plants is reported to be low and often considered as an occupational allergy. Methods Sixty five Malagasy pollen allergic patients were clinically and immunochemically investigated with regard to maize and rice pollen allergens. Pollen extracts were electrophoretically separated in 1 and 2 dimensions and IgE and IgG reactivities detected upon immunoblotting. Results When exploring the sensitization profile of Malagasy allergic patients to maize and rice pollen, it appears that a high proportion of these patients consulting during grass pollinating season were sensitized to both pollen as revealed by skin prick testing (62 vs. 59%) and IgE immunoblotting (85 vs. 40%). Several clinically relevant allergens were recognized by patients’ serum IgE in maize and rice pollen extracts. Conclusion The high levels of maize and rice pollen sensitization should be related, in this tropical region, to a specific environmental exposure including i) a proximity of the population to the allergenic sources and ii) a putative exacerbating effect of a highly polluted urban atmosphere on pollen allergenicity. Cross-reactivities between wild and cultivated grasses and also between rice and maize pollen are involved as well as some specific maize sensitizations. The presence of dense urban and peri-urban agriculture, in various African regions and worldwide, could be a high environmental risk factor for people sensitive to maize pollen. PMID:25870739

Heat-induced alterations in cashew allergen solubility and IgE binding.

PubMed

Mattison, Christopher P; Bren-Mattison, Yvette; Vant-Hull, Barry; Vargas, Aurora M; Wasserman, Richard L; Grimm, Casey C

2016-01-01

Cashew nuts are an increasingly common cause of food allergy. We compare the soluble protein profile of cashew nuts following heating. SDS-PAGE indicate that heating can alter the solubility of cashew nut proteins. The 11S legumin, Ana o 2, dominates the soluble protein content in ready to eat and mildly heated cashew nuts. However, we found that in dark-roasted cashew nuts, the soluble protein profile shifts and the 2S albumin Ana o 3 composes up to 40% of the soluble protein. Analysis of trypsin-treated extracts by LC/MS/MS indicate changes in the relative number and intensity of peptides. The relative cumulative intensity of the 5 most commonly observed Ana o 1 and 2 peptides are altered by heating, while those of the 5 most commonly observed Ana o 3 peptides remaine relatively constant. ELISA experiments indicate that there is a decrease in rabbit IgG and human serum IgE binding to soluble cashew proteins following heating. Our findings indicate that heating can alter the solubility of cashew allergens, resulting in altered IgE binding. Our results support the use of both Ana o 2 and Ana o 3 as potential cashew allergen diagnostic targets.

Effect of heat and enzymatic treatments on human IgE and rabbit IgG sensitivity to white bean allergens.

PubMed

Bousfiha, Amal; Lotfi, Aarab

2013-08-28

The aim of this study was to evaluate the sensitivity of the population of Fez and Casablanca in Morocco to dry white beans (Phaseolus Vulgaris) and to investigate the effect of food processing (heat and/or enzymatic hydrolysis by pepsin) on this sensitivity. Work was based on a bank consisting of 146 sera from patients with atopic hypersensitivity in order to evaluate specific immunoglobulin E (IgE) levels to native and processed white bean proteins by ELISA. Under the same conditions, we assessed the immunoreactivity of rabbit IgG obtained by immunization with native white bean proteins.Evaluation of specific IgE to the white bean proteins showed that 51% of children and 39% of adults had positive values. The heat treatment and pepsin hydrolysis of dry bean proteins showed a reduction of 68% of IgE binding recognition in more than 65% of all patients. After heating, all patients indicated a reduction greater than 36%. With rabbit IgG, we observed a decrease by 25% of binding under heat treatment while enzymatic digestion reduced IgG recognition by 46.6%.These findings suggest that epitopes recognized by IgE in the studied population were conformational sites whereas those recognized by rabbit IgG were probably sequential. In conclusion, these results demonstrate that the Moroccan population was very sensitive to white beans and this sensitivity could be reduced after heat treatment or enzymatic hydrolysis.

Instellar Gas Experiment (IGE): Testing interstellar gas particles to provide information on the processes of nucleosynthesis in the big bang stars and supernova

NASA Technical Reports Server (NTRS)

Lind, Don

1985-01-01

The Interstellar Gas Experiment (IGE) is designed to collect particles of the interstellar gas - a wind of interstellar media particles moving in the vicinity of the solar system. These particles will be returned to earth where the isotopic ratios of the noble gases among these particles will be measured. IGE was designed and programmed to expose 7 sets of six copper-beryllium metallic collecting foils to the flux of neutral interstellar gas particles which penetrate the heliosphere to the vicinity of the earth's orbit. These particles are trapped in the collecting foils and will be returned to earth for mass-spectrographic analysis when Long Duration Exposure Facility (LDEF) on which IGE was launched, is recovered.

Specific IgE Antibodies in Young Children with Atopic Dermatitis--Correlation of Multiple Allergen Simultaneous Immunoblot Test and ImmunoCap System.

PubMed

Konopka, Ewa; Ceregra, Aldona; Maciorkowska, Elzbieta; Surowska, Barbara; Trojanowska, Ilona; Roszko-Kirpsza, Izabela; Cukrowska, Bozena

2016-01-01

Sensitization to food allergens is a common condition in pediatric atopic dermatitis (AD). Recently, the multiple allergen simultaneous test (MAST) allowing for a comprehensive assessment of atopy has been developed, but the usefulness in young AD children is not known. The aim of this study was to determine IgE specificity in AD children using MAST and to compare the results for selected food allergens with the reference ImmunoCap system. The study enrolled 50 children up to 2 years old with a diagnosis of AD. IgE antibodies were measured with the MAST-immunoblots. Children with specific IgE levels ≥ 0.35 kU/L were identified as sensitized to allergens. Most often children were sensitized to food allergens (egg white and yolk, hazelnuts, potato, cow's milk proteins, wheat flour, codfish, and soybean), but a high percentage of them also had IgE antibodies against house dust mites (12%), grass (10%), and birch (10%). Eight percent of children were sensitized to domestic animals (cats and dogs). Almost perfect (kappa index 0.8 - 1.0) and substantial (kappa index 0.6 - 0.8) agreement between MAST and ImmunoCap was found for food allergens except codfish. Pearson's analysis of antibody classes showed a very strong correlation between two methods (r = 0.8 - 1.0) for egg white, hazelnuts, potato, cow's milk proteins, wheat flour, and soybean, and a strong correlation (r = 0.6 - 0.79) was observed for peanut, egg yolk, and codfish. The study showed the frequent occurrence of IgE antibodies against food and airborne and animal allergens in young AD children and confirmed the usefulness of MAST-immunoblots for screening of sensitization in pediatric patients.

T-helper 17-related cytokines and IgE antibodies during hepatitis A virus infection in children

PubMed Central

Trujillo-Ochoa, Jorge L; Corral-Jara, Karla F; Escobedo-Meléndez, Griselda; Realpe, Mauricio; Panduro, Arturo; Roman, Sonia; Fierro, Nora A

2015-01-01

We determined the serum IgE levels and T-helper (Th)17-related cytokines during distinct hepatitis A virus (HAV)-induced clinical courses in children. A significantly higher concentration of macrophage inflammatory protein 3α, interleukin (IL)-17E and IL-17F in HAV-infected children with intermediate liver injury compared with those with minor liver damage was found. A reduction in the IgE levels in those patients who showed the highest levels of IL-17F in the group of intermediate liver injury was found. The data suggested that the Th17-related profile is associated with the severity of HAV infection and might play a role on the modulation achieved by HAV during allergies. PMID:25946253

Nanoparticles rapidly assess specific IgE in plasma

NASA Astrophysics Data System (ADS)

Ashraf, Sarmadia; Qadri, Shahnaz; al-Ramadi, Basel; Haik, Yousef

2012-08-01

Allergy is the sixth leading cause of chronic disease in the world. This study demonstrates the feasibility of detecting allergy indicators in human plasma, noninvasively, at the point of care and with a comparable efficiency and reduced turnaround time compared with the gold standard. Peanut allergy was utilized as a model due to its widespread occurrence among the US population and fatality if not treated. The detection procedure utilized magnetic nanoparticles that were coated with an allergen layer (peanut protein extract). Peanut immunoglobulin E (IgE) was detected in concentrations close to the minimum detection range of CAP assay. The results were obtained in minutes compared with the CAP assay which requires more than 3 h.

Production of large numbers of hybridomas producing monoclonal antibodies against rat IgE using mast cell-deficient w/wv and sl/sld strains of mice.

PubMed

Rup, B J

1989-08-15

A number of different mouse strains and immunization protocols were used to attempt to make monoclonal antibodies against rat IgE for use in studies of the structure, biological activities and regulation of this class of antibody. Successful production of large numbers of monoclonal antibodies was achieved when mast cell deficient (w/wv and sl/sld) but not conventional (BALB/c, CAF1 or SJL) mice were used. These results suggest that the poor response of conventional strains of mice to rat IgE may be due to the presence of mast cells bearing high affinity receptors for IgE in these mice.

Conjunctivitis and Total IgE in Lacrimal Fluid: Lacrytest Screening

PubMed Central

Monzón, Susana; Arrondo, Elena; Bartra, Joan; Torres, Ferran; Basagaña, María; San Miguel, M. del Mar; Alonso, Rosario; Cisteró-Bahima, Anna

2009-01-01

Total tear IgE has been considered to play an important role in allergic conjunctivitis, and measurement has been considered useful for diagnosis. The aim of this study was to ascertain whether Lacrytest®, a new commercialised method to detect IgE levels in lacrimal fluid, could constitute a screening test for the diagnosis of allergic conjunctivitis. This was a cross-sectional study. Patients with seasonal and perennial allergic conjunctivitis, vernal keratoconjunctivitis and a control group were included. Clinical history, ophthalmic examination, skin prick test and conjunctival provocation test were obtained. Lacrytest® was later performed in all groups. Fifty-four patients were enrolled: thirty with IgE-mediated conjunctivitis and, nine with vernal keratoconjunctivitis and fifteen controls. Lacrytest® was negative in all controls, positive in 20% of the IgE-mediated conjunctivitis group and in 88.9% of the vernal keratoconjunctivitis group. Global statistically-significant differences were found among the three groups (P = .003). Sensitivity of the test in the IgE-mediated conjunctivitis group was 20%, specificity 100%, positive predictive value 100%, and negative predictive value 38.46%, while in VKC sensitivity was 88.88%, specificity 100%, positive predictive value 100%, and negative predictive value 93.75%. Our data confirm that this test is not useful for screening allergic conjunctivitis. Lacrytest®, while not providing any useful information to an allergist, could be helpful for ophthalmologists to confirm an IgE-mediated or VKC conjunctivitis. PMID:20975798

Agreement between allergen-specific IgE assays and ensuing immunotherapy recommendations from four commercial laboratories in the USA.

PubMed

Plant, Jon D; Neradelik, Moni B; Polissar, Nayak L; Fadok, Valerie A; Scott, Brian A

2014-02-01

Canine allergen-specific IgE assays in the USA are not subjected to an independent laboratory reliability monitoring programme. The aim of this study was to evaluate the agreement of diagnostic results and treatment recommendations of four serum IgE assays commercially available in the USA. Replicate serum samples from 10 atopic dogs were submitted to each of four laboratories for allergen-specific IgE assays (ACTT(®) , VARL Liquid Gold, ALLERCEPT(®) and Greer(®) Aller-g-complete(®) ). The interlaboratory agreement of standard, regional panels and ensuing treatment recommendations were analysed with the kappa statistic (κ) to account for agreement that might occur merely by chance. Six comparisons of pairs of laboratories and overall agreement among laboratories were analysed for ungrouped allergens (as tested) and also with allergens grouped according to reported cross-reactivity and taxonomy. The overall chance-corrected agreement of the positive/negative test results for ungrouped and grouped allergens was slight (κ = 0.14 and 0.13, respectively). Subset analysis of the laboratory pair with the highest level of diagnostic agreement (κ = 0.36) found slight agreement (κ = 0.13) for ungrouped plants and fungi, but substantial agreement (κ = 0.71) for ungrouped mites. The overall agreement of the treatment recommendations was slight (κ = 0.11). Altogether, 85.1% of ungrouped allergen treatment recommendations were unique to one laboratory or another. Our study indicated that the choice of IgE assay may have a major influence on the positive/negative results and ensuing treatment recommendations. © 2014 The Authors. Veterinary Dermatology published by John Wiley & Sons Ltd on behalf of the ESVD and the ACVD.

Patterns of IgE responses to multiple allergen components and clinical symptoms at age 11 years

PubMed Central

Simpson, Angela; Lazic, Nevena; Belgrave, Danielle C.M.; Johnson, Phil; Bishop, Christopher; Mills, Clare; Custovic, Adnan

2015-01-01

Background The relationship between sensitization to allergens and disease is complex. Objective We sought to identify patterns of response to a broad range of allergen components and investigate associations with asthma, eczema, and hay fever. Methods Serum specific IgE levels to 112 allergen components were measured by using a multiplex array (Immuno Solid-phase Allergen Chip) in a population-based birth cohort. Latent variable modeling was used to identify underlying patterns of component-specific IgE responses; these patterns were then related to asthma, eczema, and hay fever. Results Two hundred twenty-one of 461 children had IgE to 1 or more components. Seventy-one of the 112 components were recognized by 3 or more children. By using latent variable modeling, 61 allergen components clustered into 3 component groups (CG1, CG2, and CG3); protein families within each CG were exclusive to that group. CG1 comprised 27 components from 8 plant protein families. CG2 comprised 7 components of mite allergens from 3 protein families. CG3 included 27 components of plant, animal, and fungal origin from 12 protein families. Each CG included components from different biological sources with structural homology and also nonhomologous proteins arising from the same biological source. Sensitization to CG3 was most strongly associated with asthma (odds ratio [OR], 8.20; 95% CI, 3.49-19.24; P < .001) and lower FEV1 (P < .001). Sensitization to CG1 was associated with hay fever (OR, 12.79; 95% CI, 6.84-23.90; P < .001). Sensitization to CG2 was associated with both asthma (OR, 3.60; 95% CI, 2.05-6.29) and hay fever (OR, 2.52; 95% CI, 1.38-4.61). Conclusions Latent variable modeling with a large number of allergen components identified 3 patterns of IgE responses, each including different protein families. In 11-year-old children the pattern of response to components of multiple allergens appeared to be associated with current asthma and hay fever but not eczema. PMID

Sensitization with 7S globulins from peanut, hazelnut, soy or pea induces IgE with different biological activities which are modified by soy tolerance.

PubMed

Kroghsbo, Stine; Bøgh, Katrine L; Rigby, Neil M; Mills, E N Clare; Rogers, Adrian; Madsen, Charlotte B

2011-01-01

It is not known why some foods sensitizing via the gastrointestinal tract are prevalent allergenic foods and others are not. Eating habits, processing, and the food matrix have been suggested to influence the allergenicity of a given food. Factors related to protein structure, such as stability to digestion, have also been suggested. 7S globulins from peanut, hazelnut, soy, and pea were studied to determine whether related proteins would induce a similar sensitization when removed from their 'normal' matrix. Brown Norway rats (soy tolerant or nontolerant) were immunized i.p. 3 times with 100 μg purified peanut, hazelnut, soy, or pea 7S without adjuvant. Sera were analyzed for specific antibodies by different ELISAs (IgG1, IgG2a, and IgE), inhibition ELISA, and rat basophilic leukemia cell assay. The 4 related 7S globulins induced a response with an almost identical level of specific antibodies, but peanut 7S induced IgE of higher avidity than hazelnut and pea 7S which, again, had a higher avidity than IgE induced by soy 7S. Soy tolerance reduced the functionality of IgE without influencing antibody titers. Although the 4 7S globulins are structurally related allergens, they induce antibodies with different antigen-binding characteristics. Peanut 7S induces IgE of a higher avidity than hazelnut and pea 7S which, again, has a higher avidity than IgE induced by soy 7S. We also show that soy tolerance influences the function of antibodies to peanut 7S. These findings may help explain how antibodies of different clinical significances can develop in different individuals sensitized to the same allergen. Copyright © 2011 S. Karger AG, Basel.

Molecular allergy diagnostics using IgE singleplex determinations: methodological and practical considerations for use in clinical routine: Part 18 of the Series Molecular Allergology.

PubMed

Kleine-Tebbe, Jörg; Jakob, Thilo

Allergen molecules (synonyms: single allergens, allergen components) open up new horizons for the targeted allergen-specific diagnostics of immunoglobulin E (IgE) in singleplex determination. The following rationales support the targeted use of allergen molecules and, more importantly, improve test properties: (1) increased test sensitivity ("analytical sensitivity"), particularly when important allergens are under-represented or lacking in the extract; (2) improved test selectivity (analytical specificity), particularly when the selected IgE repertoire against an allergen yields additional information on: (a) potential risk, (b) possible cross-reactivity, or (c) primary (species-specific) sensitization. However, the appropriate indication for the use of single allergens can only be established on a case-by-case basis (depending on the clinical context and previous history) and in an allergen-specific manner (depending on the allergen source and the single allergens available), rather than in a standardized way. Numerous investigations on suspected food allergy, insect venom allergy, or sensitization to respiratory allergens have meanwhile demonstrated the successful use of defined molecules for allergen-specific singleplex IgE diagnosis. Specific IgE to single allergens is limited in its suitability to predict the clinical relevance of sensitivity on an individual basis. In food allergies, one can at best identify the relative risk of a clinical reaction on the basis of an IgE profile, but no absolutely reliable prediction on (future) tolerance can be made. Ultimately, the clinical relevance of all IgE findings depends on the presence of corresponding symptoms and can only be assessed on an individual basis (previous history, symptom log, and provocation testing with the relevant allergen source where appropriate). Thus, also in molecular allergology, the treating physician and not the test result should determine the clinical relevance of diagnostic findings

Clinical routine utility of basophil activation testing for diagnosis of hymenoptera-allergic patients with emphasis on individuals with negative venom-specific IgE antibodies.

PubMed

Korošec, Peter; Šilar, Mira; Eržen, Renato; Čelesnik, Nina; Bajrović, Nissera; Zidarn, Mihaela; Košnik, Mitja

2013-01-01

Previous reports suggest the usefulness of basophil activation testing (BAT) in Hymenoptera-allergic patients with negative venom-specific IgE antibodies. We sought to evaluate the diagnostic utility of this testing in a routine clinical laboratory setting. Twenty-one patients with anaphylactic reactions to Hymenoptera sting (median grade III) and negative venom-specific IgE were routinely and prospectively tested with BAT. We were able to diagnose 81% (17 of 21) of patients with BAT and 57% (12 of 21) with intradermal skin testing. Three wasp venom-allergic patients showed IgE positivity to rVes v 5. Four patients (19%) were negative for all tests. In the case of double-positive BAT, the culprit insect correlated with the venom that induced a significantly higher basophil response. BAT allows the identification of severe Hymenoptera-allergic patients with negative specific IgE and skin tests. The routine use of this cellular test should facilitate prescription of venom immunotherapy in complex cases with inconclusive diagnostic results. Copyright © 2013 S. Karger AG, Basel.

Analysis of calcium-induced conformational changes in calcium-binding allergens and quantitative determination of their IgE binding properties.

PubMed

Parody, Nuria; Fuertes, Miguel Angel; Alonso, Carlos; Pico de Coaña, Yago

2013-01-01

The polcalcin family is one of the most epidemiologically relevant families of calcium-binding allergens. Polcalcins are potent plant allergens that contain one or several EF-hand motifs and their allergenicity is primarily associated with the Ca(2+)-bound form of the protein. Conformation, stability, as well as IgE recognition of calcium-binding allergens greatly depend on the presence of protein-bound calcium ions. We describe a protocol that uses three techniques (SDS-PAGE, circular dichroism spectroscopy, and ELISA) to describe the effects that calcium has on the structural changes in an allergen and its IgE binding properties.

[Multiple myeloma (IgG-kappa) infiltrating central nervous system, lymph nodes, liver, and kidneys, and with elevation of IgE].

PubMed

Toyota, Shigeo; Nakamura, Norihiko; Dan, Kazuo

2004-05-01

A 63-year-old man was admitted because of general malaise, fever, headache, generalized lymphadenopathy and hepatomegaly in July 2002. He was diagnosed as having multiple myeloma (MM) (IgG-kappa type) with atypical plasma cells in the bone marrow, lymph nodes and cerebrospinal fluid. Systemic and intrathecal chemotherapy were effective. Because of an increase of polyclonal IgE, electrophoretic patterns revealed an M-peak which was not as sharp as that in IgG myeloma. IgE production is not impaired by the pathologic process in MM patients.

Allergen-specific IgG antibodies purified from mite-allergic patients sera block the IgE recognition of Dermatophagoides pteronyssinus antigens: an in vitro study.

PubMed

Siman, Isabella Lima; de Aquino, Lais Martins; Ynoue, Leandro Hideki; Miranda, Juliana Silva; Pajuaba, Ana Claudia Arantes Marquez; Cunha-Júnior, Jair Pereira; Silva, Deise Aparecida Oliveira; Taketomi, Ernesto Akio

2013-01-01

One of the purposes of specific immunotherapy (SIT) is to modulate humoral immune response against allergens with significant increases in allergen-specific IgG levels, commonly associated with blocking activity. The present study investigated in vitro blocking activity of allergen-specific IgG antibodies on IgE reactivity to Dermatophagoides pteronyssinus (Dpt) in sera from atopic patients. Dpt-specific IgG antibodies were purified by ammonium sulfate precipitation followed by protein-G affinity chromatography. Purity was checked by SDS-PAGE and immunoreactivity by slot-blot and immunoblot assays. The blocking activity was evaluated by inhibition ELISA. The electrophoretic profile of the ammonium sulfate precipitated fraction showed strongly stained bands in ligand fraction after chromatography, compatible with molecular weight of human whole IgG molecule. The purity degree was confirmed by detecting strong immunoreactivity to IgG, negligible to IgA, and no reactivity to IgE and IgM. Dpt-specific IgG fraction was capable of significantly reducing levels of IgE anti-Dpt, resulting in 35%-51% inhibition of IgE reactivity to Dpt in atopic patients sera. This study showed that allergen-specific IgG antibodies purified from mite-allergic patients sera block the IgE recognition of Dermatophagoides pteronyssinus antigens. This approach reinforces that intermittent measurement of serum allergen-specific IgG antibodies will be an important objective laboratorial parameter that will help specialists to follow their patients under SIT.

Negativization rates of IgE radioimmunoassay and basophil activation test in immediate reactions to penicillins.

PubMed

Fernández, T D; Torres, M J; Blanca-López, N; Rodríguez-Bada, J L; Gomez, E; Canto, G; Mayorga, C; Blanca, M

2009-02-01

Skin test sensitivity in patients with immediate allergy to penicillins tends to decrease over time, but no information is available concerning in vitro tests. We analysed the negativization rates of two in vitro methods that determine specific immunoglobulin E (IgE) antibodies, the basophil activation test using flow cytometry (BAT) and the radioallergosorbent test (RAST), in immediate allergic reactions to penicillins. Forty-one patients with immediate allergic reactions to amoxicillin were followed up over a 4-year period. BAT and RAST were performed at 6-month intervals. Patients were randomized into groups: Group I, skin tests carried out at regular intervals; Group II, skin tests made only at the beginning of the study. Differences were observed between RAST and BAT (P < 0.01), the latter showing earlier negativization. Considering different haptens, significant differences for the rate of negativization were only found for amoxicillin (P < 0.05). Comparisons between Groups I (n = 10) and II (n = 31) showed a tendency to become negative later in Group I with RAST. Levels of specific IgE antibodies tended to decrease over time in patients with immediate allergic reactions to amoxicillin. Conversion to negative took longer for the RAST assay, although the differences were only detected with the amoxicillin hapten. Skin testing influenced the rate of negativization of the RAST assay, contributing to maintenance of in vitro sensitivity. Because of the loss of sensitivity over time, the determination of specific IgE antibodies to penicillins in patients with immediate allergic reactions must be done as soon as possible after the reaction.

Analytical criteria for performance characteristics of IgE binding methods for evaluating safety of biotech food products.

PubMed

Holzhauser, Thomas; Ree, Ronald van; Poulsen, Lars K; Bannon, Gary A

2008-10-01

There is detailed guidance on how to perform bioinformatic analyses and enzymatic degradation studies for genetically modified crops under consideration for approval by regulatory agencies; however, there is no consensus in the scientific community on the details of how to perform IgE serum studies. IgE serum studies are an important safety component to acceptance of genetically modified crops when the introduced protein is novel, the introduced protein is similar to known allergens, or the crop is allergenic. In this manuscript, we describe the characteristics of the reagents, validation of assay performance, and data analysis necessary to optimize the information obtained from serum testing of novel proteins and genetically modified (GM) crops and to make results more accurate and comparable between different investigations.

Mutational epitope analysis of Pru av 1 and Api g 1, the major allergens of cherry (Prunus avium) and celery (Apium graveolens): correlating IgE reactivity with three-dimensional structure.

PubMed Central

Neudecker, Philipp; Lehmann, Katrin; Nerkamp, Jörg; Haase, Tanja; Wangorsch, Andrea; Fötisch, Kay; Hoffmann, Silke; Rösch, Paul; Vieths, Stefan; Scheurer, Stephan

2003-01-01

Birch pollinosis is often accompanied by adverse reactions to food due to pollen-allergen specific IgE cross-reacting with homologous food allergens. The tertiary structure of Pru av 1, the major cherry (Prunus avium) allergen, for example, is nearly identical with Bet v 1, the major birch (Betula verrucosa) pollen allergen. In order to define cross-reactive IgE epitopes, we generated and analysed mutants of Pru av 1 and Api g 1.0101, the major celery (Apium graveolens) allergen, by immunoblotting, EAST (enzyme allergosorbent test), CD and NMR spectroscopy. The mutation of Glu45 to Trp45 in the P-loop region, a known IgE epitope of Bet v 1, significantly reduced IgE binding to Pru av 1 in a subgroup of cherry-allergic patients. The backbone conformation of Pru av 1 wild-type is conserved in the three-dimensional structure of Pru av 1 Trp45, demonstrating that the side chain of Glu45 is involved in a cross-reactive IgE epitope. Accordingly, for a subgroup of celery-allergic patients, IgE binding to the homologous celery allergen Api g 1.0101 was enhanced by the mutation of Lys44 to Glu. The almost complete loss of IgE reactivity to the Pru av 1 Pro112 mutant is due to disruption of its tertiary structure. Neither the mutation Ala112 nor deletion of the C-terminal residues 155-159 influenced IgE binding to Pru av 1. In conclusion, the structure of the P-loop partially explains the cross-reactivity pattern, and modulation of IgE-binding by site-directed mutagenesis is a promising approach to develop hypo-allergenic variants for patient-tailored specific immunotherapy. PMID:12943529

Polymorphisms of endotoxin pathway and endotoxin exposure: in vitro IgE synthesis and replication in a birth cohort.

PubMed

Sahiner, U M; Semic-Jusufagic, A; Curtin, J A; Birben, E; Belgrave, D; Sackesen, C; Simpson, A; Yavuz, T S; Akdis, C A; Custovic, A; Kalayci, O

2014-12-01

Genetic variants in endotoxin signaling pathway are important in modulating the effect of environmental endotoxin on asthma and atopic phenotypes. Our objective was to determine the single nucleotide polymorphisms (SNPs) in the endotoxin signaling pathway that may influence in vitro IgE synthesis and to investigate the relationship between these variants and endotoxin exposure in relation to the development of asthma and atopy in a birth cohort. Peripheral blood mononuclear cells from 45 children with asthma were stimulated with 2 and 200 ng/ml lipopolysaccharide in vitro and IgE was measured in the culture supernatants. Children were genotyped for 121 SNPs from 30 genes in the endotoxin signaling pathway. Variants with a dose-response IgE production in relation to lipopolysaccharide (LPS) were selected for replication in a population-based birth cohort, in which we investigated the interaction between these SNPs and endotoxin exposure in relation to airway hyper-responsiveness, wheeze, and atopic sensitization. Twenty-one SNPs in nine genes (CD14, TLR4, IRF3, TRAF-6, TIRAP, TRIF, IKK-1, ST-2, SOCS1) were found to modulate the effect of endotoxin on in vitro IgE synthesis, with six displaying high linkage disequilibrium. Of the remaining 15 SNPs, for seven we found significant relationships between genotype and endotoxin exposure in the genetic association study in relation to symptomatic airway hyper-responsiveness (CD14-rs2915863 and rs2569191, TRIF-rs4807000), current wheeze (ST-2-rs17639215, IKK-1-rs2230804, and TRIF-rs4807000), and atopy (CD14-rs2915863 and rs2569192, TRAF-6-rs5030411, and IKK-1-rs2230804). Variants in the endotoxin signaling pathway are important determinants of asthma and atopy. The genotype effect is a function of the environmental endotoxin exposure. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

IgE sensitization to gelatin: the probable role of gelatin-containing diphtheria-tetanus-acellular pertussis (DTaP) vaccines.

PubMed

Sakaguchi, M; Inouye, S

2000-04-03

We recently found that most events of anaphylaxis to live attenuated viral vaccines containing gelatin as a stabilizer might be caused by the gelatin. However, the mechanism that the children were sensitized to gelatin was unclear. In Japan, both diphtheria-tetanus-acellular pertussis (DTaP) vaccines with and without gelatin are available. We explored the possibility that gelatin-containing DTaP vaccines before live viral vaccines sensitize children to gelatin. We received the serum samples of 87 children who had systemic immediate-type reactions including anaphylaxis to the vaccines from both physicians and vaccine manufacturers throughout Japan. We then surveyed the DTaP vaccination histories of the children who demonstrated anti-gelatin IgE. Of the above 87 children, 79 (91%) had anti-gelatin IgE. We successfully collected DTaP vaccination histories including the manufacturers' names and numbers of doses on 55 children. Only one child had not received any DTaP vaccine, the other 54 had received gelatin-containing DTaP vaccines and none received gelatin-free DTaP vaccines. We concluded that there was a strong causal relationship between gelatin-containing DTaP vaccination, anti-gelatin IgE production, and risk of anaphylaxis following subsequent immunization with live viral vaccines which contain a larger amount of gelatin.

CD23 surface density on B cells is associated with IgE levels and determines IgE-facilitated allergen uptake, as well as activation of allergen-specific T cells.

PubMed

Selb, Regina; Eckl-Dorna, Julia; Neunkirchner, Alina; Schmetterer, Klaus; Marth, Katharina; Gamper, Jutta; Jahn-Schmid, Beatrice; Pickl, Winfried F; Valenta, Rudolf; Niederberger, Verena

2017-01-01

Increasing evidence suggests that the low-affinity receptor for IgE, CD23, plays an important role in controlling the activity of allergen-specific T cells through IgE-facilitated allergen presentation. We sought to determine the number of CD23 molecules on immune cells in allergic patients and to investigate whether the number of CD23 molecules on antigen-presenting cells is associated with IgE levels and influences allergen uptake and allergen-specific T-cell activation. Numbers of CD23 molecules on immune cells of allergic patients were quantified by using flow cytometry with QuantiBRITE beads and compared with total and allergen-specific IgE levels, as well as with allergen-induced immediate skin reactivity. Allergen uptake and allergen-specific T-cell activation in relation to CD23 surface density were determined by using flow cytometry in combination with confocal microscopy and T cells transfected with the T-cell receptor specific for the birch pollen allergen Bet v 1, respectively. Defined IgE-allergen immune complexes were formed with human monoclonal allergen-specific IgE and Bet v 1. In allergic patients the vast majority of CD23 molecules were expressed on naive IgD + B cells. The density of CD23 molecules on B cells but not the number of CD23 + cells correlated with total IgE levels (R S  = 0.53, P = .03) and allergen-induced skin reactions (R S  = 0.63, P = .008). Uptake of allergen-IgE complexes into B cells and activation of allergen-specific T cells depended on IgE binding to CD23 and were associated with CD23 surface density. Addition of monoclonal IgE to cultured PBMCs significantly (P = .04) increased CD23 expression on B cells. CD23 surface density on B cells of allergic patients is correlated with allergen-specific IgE levels and determines allergen uptake and subsequent activation of T cells. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Work-related allergy and asthma in spice mill workers - The impact of processing dried spices on IgE reactivity patterns.

PubMed

van der Walt, Anita; Lopata, Andreas L; Nieuwenhuizen, Natalie E; Jeebhay, Mohamed F

2010-01-01

Three spice mill workers developed work-related allergy and asthma after prolonged exposure to high levels (>10 mg/m(3)) of inhalable spice dust. Patterns of sensitization to a variety of spices and putative allergens were identified. Work-related allergy and asthma were assessed on history, clinical evaluation, pulmonary function and fractional exhaled nitric oxide. Specific IgE reactivity to a range of common inhalant, food and spice allergens was evaluated using ImmunoCAP and allergen microarray. The presence of non-IgE-mediated reactions was determined by basophil stimulation (CAST-ELISA). Specific allergens were identified by immunoblotting to extracts of raw and dried processed garlic, onion and chili pepper. Asthma was confirmed in all 3 subjects, with work-related patterns prominent in worker 1 and 3. Sensitization to multiple spices and pollen was observed in both atopic workers 1 and 2, whereas garlic and chili pepper sensitization featured in all 3 workers. Microarray analysis demonstrated prominent profilin reactivity in atopic worker 2. Immunoblotting demonstrated a 50-kDa cross-reactive allergen in garlic and onion, and allergens of approximately 40 and 52 kDa in chili pepper. Dry powdered garlic and onion demonstrated greater IgE binding. This study demonstrated IgE reactivity to multiple spice allergens in workers exposed to high levels of inhalable spice dust. Processed garlic and onion powder demonstrated stronger IgE reactivity than the raw plant. Atopy and polysensitization to various plant profilins, suggesting pollen-food syndrome, represent additional risk factors for sensitizer-induced work-related asthma in spice mill workers. 2010 S. Karger AG, Basel.

Serum concentrations of allergen-specific IgE in horses with equine recurrent airway obstruction and healthy controls assessed by ELISA.

PubMed

Niedzwiedz, Artur; Jaworski, Zbigniew; Kubiak, Krzysztof

2015-09-01

Equine recurrent airway obstruction (RAO), also known as heaves, is one of the most common respiratory problems in older horses. When RAO-affected horses stay pastured or in a dust-free environment for a prolonged time, clinical signs as well as airway inflammation wane. A number of environmental, immunologic, infectious, and genetic factors play an important role in the pathogenesis of RAO, and the immunologic basis of this disease is still poorly understood. The aim of this study was to investigate the concentrations of allergen-specific IgE in the serum of horses suffering from RAO and healthy controls. The study included a group of 14 adult Polish Konik horses, kept in a standardized environment, and divided into 2 groups: 7 horses which did not have any respiratory problems comprised the control group and 7 horses with a history of RAO constituted the study group. A clinical and laboratory evaluation, endoscopic examination, and bronchoalveolar lavage (BAL) were performed in all horses. Sera of all horses were tested against allergens from 9 molds and 3 mites using the Heska Allercept assay. In the serologic tests, a statistically significant difference between both groups was found for specific IgE against mites, wherein Tyrophagus putrescentia correlated most clearly with RAO. There was no difference between groups for IgE specific against molds. On the basis of our observations and results, we conclude that RAO is associated with increased serum concentrations of specific serum IgE against mites, in particular T putrescentia. © 2015 American Society for Veterinary Clinical Pathology.

Cross-reactivity of IgE antibodies with allergens in birch pollen, fruits and vegetables.

PubMed

Halmepuro, L; Vuontela, K; Kalimo, K; Björkstén, F

1984-01-01

Allergens extracted from apple, carrot, celery tuber and orange were coupled to radioallergosorbent test (RAST) discs. These and commercial birch, mugwort and timothy pollen discs were used to study sera from 90 patients for the presence of IgE antibodies which react with the allergens in question. Individual sera frequently gave positive results with several discs - in particular with birch pollen, apple, carrot and celery tuber discs. If IgE antibodies to birch pollen or apple allergens were detected, there was a 90% chance of antibodies being found also to the second one of these two source materials. Skin tests and patient histories indicated similar clustering of allergies. RAST inhibition experiments showed that the clustering phenomenon was due to cross-reactivity. All immunological determinants in fruits and vegetables appeared to be present also in birch pollen, but all birch pollen determinants were not present in fruits and vegetables. 45 children with atopic dermatitis were studied to establish whether a positive orange RAST would correlate with a history of atopic dermatitis aggravated by orange. The results were negative.

Are allergic multimorbidities and IgE polysensitization associated with the persistence or re-occurrence of foetal type 2 signalling? The MeDALL hypothesis.

PubMed

Bousquet, J; Anto, J M; Wickman, M; Keil, T; Valenta, R; Haahtela, T; Lodrup Carlsen, K; van Hage, M; Akdis, C; Bachert, C; Akdis, M; Auffray, C; Annesi-Maesano, I; Bindslev-Jensen, C; Cambon-Thomsen, A; Carlsen, K H; Chatzi, L; Forastiere, F; Garcia-Aymerich, J; Gehrig, U; Guerra, S; Heinrich, J; Koppelman, G H; Kowalski, M L; Lambrecht, B; Lupinek, C; Maier, D; Melén, E; Momas, I; Palkonen, S; Pinart, M; Postma, D; Siroux, V; Smit, H A; Sunyer, J; Wright, J; Zuberbier, T; Arshad, S H; Nadif, R; Thijs, C; Andersson, N; Asarnoj, A; Ballardini, N; Ballereau, S; Bedbrook, A; Benet, M; Bergstrom, A; Brunekreef, B; Burte, E; Calderon, M; De Carlo, G; Demoly, P; Eller, E; Fantini, M P; Hammad, H; Hohman, C; Just, J; Kerkhof, M; Kogevinas, M; Kull, I; Lau, S; Lemonnier, N; Mommers, M; Nawijn, M; Neubauer, A; Oddie, S; Pellet, J; Pin, I; Porta, D; Saes, Y; Skrindo, I; Tischer, C G; Torrent, M; von Hertzen, L

2015-09-01

Allergic diseases [asthma, rhinitis and atopic dermatitis (AD)] are complex. They are associated with allergen-specific IgE and nonallergic mechanisms that may coexist in the same patient. In addition, these diseases tend to cluster and patients present concomitant or consecutive diseases (multimorbidity). IgE sensitization should be considered as a quantitative trait. Important clinical and immunological differences exist between mono- and polysensitized subjects. Multimorbidities of allergic diseases share common causal mechanisms that are only partly IgE-mediated. Persistence of allergic diseases over time is associated with multimorbidity and/or IgE polysensitization. The importance of the family history of allergy may decrease with age. This review puts forward the hypothesis that allergic multimorbidities and IgE polysensitization are associated and related to the persistence or re-occurrence of foetal type 2 signalling. Asthma, rhinitis and AD are manifestations of a common systemic immune imbalance (mesodermal origin) with specific patterns of remodelling (ectodermal or endodermal origin). This study proposes a new classification of IgE-mediated allergic diseases that allows the definition of novel phenotypes to (i) better understand genetic and epigenetic mechanisms, (ii) better stratify allergic preschool children for prognosis and (iii) propose novel strategies of treatment and prevention. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Downregulation of IL-8, ECP, and total IgE in the tears of patients with atopic keratoconjunctivitis treated with rebamipide eyedrops.

PubMed

Ueta, Mayumi; Shoji, Jun; Sotozono, Chie; Kinoshita, Shigeru

2014-01-01

Rebamipide eyedrops are approved in Japan for the treatment of dry eye disease. Some patients with allergic conjunctival diseases also manifest dry eye. Earlier we reported that rebamipide suppressed polyI:C-induced inflammatory cytokines in human conjunctival epithelial cells. In the current study we examined the effect of rebamipide eyedrops on the level of interleukin-8 (IL-8), eosinophil cationic protein (ECP), and total IgE on the ocular surface. We prescribed rebamipide eyedrops to patients with atopic keratoconjunctivitis (AKC) who presented with dry eye (6 eyes in 4 AKC patients) and measured the IL-8, ECP, and total IgE levels in their tears before- and 2, and 4-6 weeks after the start of rebamipide treatment. To measure the IL-8 and total IgE levels in their tears we used BD™ CBA Flex sets; ECP measurements were with ELISA. The level of IL-8, ECP, and total IgE in the tears of AKC patients was reduced significantly 4-6 weeks after the start of rebamipide treatment. We also recorded subjective symptoms associated with AKC, e.g. itching, foreign body sensation, and eye mucus discharge, by using a patient questionnaire. Their subjective symptoms associated with AKC were also significantly ameliorated at 2 and 4-6 weeks. Our observations suggest that the anti-inflammatory effects of rebamipide eyedrops help to combat human ocular surface inflammation and that they may be a new effective therapy in patients with AKC.

Pregnant women have increased incidence of IgE autoantibodies reactive with the skin and placental antigen BP180 (type XVII collagen)

PubMed Central

Noe, Megan H.; Messingham, Kelly A.N.; Brandt, Debra S.; Andrews, Janet I.; Fairley, Janet A.

2016-01-01

BP180 (type XVII collagen) is a transmembrane protein expressed in a variety of cell types. It is also the target of autoantibodies in cutaneous autoimmune disease including bullous pemphigoid and pemphigoid gestationis, a disease unique to pregnancy. The purpose of this study was to determine the prevalence and specificity of cutaneous autoantibodies in a cohort of pregnant women. De-identified sera were collected from pregnant women (n = 299) and from non-pregnant controls (n = 134). Sera were analyzed by ELISA for the presence of IgG and IgE autoantibodies directed against several cutaneous autoantigens. IgE antibodies against the NC16A domain of BP180 were detected in 7.7% of pregnant women, compared to 2.2% of healthy controls (p = 0.01). No increase in total or cutaneous autoantigen specific IgG was seen. Total serum IgE was within the normal range. Full-length BP180 was detected by western immunoblot in epidermal, keratinocyte, placental and cytotrophoblast (CTB) cell lysates. Furthermore, flow cytometry and indirect immunofluorescence confirmed the expression of BP180 on the surface of cultured CTBs. Finally, it was demonstrated that IgE antibodies in the pregnancy sera labeled not only cultured CTBs, but also the placental amnion and cutaneous basement membrane zone using indirect immunofluorescence. We conclude that some pregnant women develop antibodies specific for BP180, and that these autoantibodies are capable of binding both CTB and the placental amnion, potentially affecting placental function. PMID:20471095

Differential Decline in Leishmania Membrane Antigen-Specific Immunoglobulin G (IgG), IgM, IgE, and IgG Subclass Antibodies in Indian Kala-Azar Patients after Chemotherapy

PubMed Central

Anam, Khairul; Afrin, Farhat; Banerjee, Dwijadas; Pramanik, Netai; Guha, Subhasis K.; Goswami, Rama P.; Saha, Shiben K.; Ali, Nahid

1999-01-01

Pathogenesis in kala-azar is associated with depressed cellular immunity and significant elevation of antileishmanial antibodies. Since these antibodies are present even after cure, analysis of the parasite-specific isotypes and immunoglobulin G (IgG) subclasses in kala-azar patients may shed new light on the immune responses during progression and resolution of infection. Using leishmanial membrane antigenic extracts, we investigated the relative levels of specific IgG, IgM, IgA, IgE, and IgG subclasses in Indian kala-azar patient sera during disease, drug resistance, and cure. Acute-phase sera showed strong stimulation of IgG, followed by IgE and IgM and lastly by IgA antibodies. IgG subclass analysis revealed expression of all of the subclasses, with a predominance of IgG1 during disease. Following sodium stibogluconate (SAG) resistance, the levels of IgG, IgM, IgE, and IgG4 remained constant, while there was a decrease in the titers of IgG2 and IgG3. In contrast, a significant (2.2-fold) increase in IgG1 was observed in these individuals. Cure, in both SAG-responsive and unresponsive patients, correlated with a decline in the levels of IgG, IgM, IgE, and all of the IgG subclasses. The stimulation of IgG1 and the persistence, most importantly, of IgE and IgG4 following drug resistance, along with a decline in IgE, IgG4, and IgG1 with cure, demonstrate the potential of these isotypes as possible markers for monitoring effective treatment in kala-azar. PMID:10569788

Prevalence of anti-gelatin IgE antibodies in people with anaphylaxis after measles-mumps rubella vaccine in the United States.

PubMed

Pool, Vitali; Braun, M Miles; Kelso, John M; Mootrey, Gina; Chen, Robert T; Yunginger, John W; Jacobson, Robert M; Gargiullo, Paul M

2002-12-01

Anaphylaxis after immunization, although rare, is serious and potentially life-threatening. Understanding risk factors for this reaction is therefore important. Gelatin is added to many vaccines as a heat stabilizer. Japanese researchers have demonstrated a strong association between immediate hypersensitivity reactions to measles, mumps, rubella, varicella, and Japanese encephalitis immunizations and subsequent detection of anti-gelatin immunoglobulin E (IgE) antibodies. They suggested that previous receipt by these patients of diphtheria-tetanus-acellular pertussis vaccines with trace amounts of gelatin was responsible for the sensitization. We aimed to assess whether a similar association exists for vaccinees in the United States who reported anaphylaxis after receipt of measles-mumps-rubella (MMR) or measles vaccines and to review recent trends in reporting of hypersensitivity reactions. We conducted a retrospective case-control study. Cases of anaphylaxis that met a predefined case definition were identified from the US Vaccine Adverse Event Reporting System (VAERS). Mayo Clinic patients who received MMR vaccine uneventfully served as controls. The study subjects were interviewed to obtain the history of allergies. Sera from study subjects and their matched controls were tested for IgE antibodies to gelatin, whole egg, and vaccine viral antigens using solid-phase radioimmunoassay. Data from the Biologics Surveillance System on annual numbers of doses of MMR and varicella vaccines distributed in the United States were used to evaluate possible changes in reporting of selected allergic adverse events. Fifty-seven study subjects were recruited into the study and interviewed. Of these, 22 provided serum samples for IgE testing. Twenty-seven subjects served as a comparison group and provided a sample for IgE testing; 21 of these completed an allergy history questionnaire. Self-reported history of food allergies was present more frequently in the interviewed study

[Effect of Broncho-Vaxom on serum IgE and IgG levels in patients with bronchial asthma and chronic obstructive lung disease. A placebo-controlled double-blind study].

PubMed

Weiss, S; Fux, T

1987-09-26

In a double-blind study of 33 patients with bronchial asthma or chronic obstructive pulmonary disease, of whom 17 had proven atopies, the results showed a distinct diminution of the mean IgE level in the atopic patients at the end of 1-month treatment with Broncho-Vaxom, though not attaining statistical significance (trend with p less than 0.10), compared to a slight increase under placebo. Simultaneously the mean IgG level increased slightly in the atopic patients under Broncho-Vaxom and remained stable in the patients under placebo (p less than 0.10). The IgE and IgG values of the non-atopic patients in both treatment groups remained practically unchanged. Considering the small number of patients in each group, and the clear tendency towards a diminution of the IgE level, it may be concluded that the administration of Broncho-Vaxom to atopic patients does not lead to an increased IgE level but, on the contrary, seems rather to favour a decrease.

IgE sensitization to Thaumetopoea pityocampa : diagnostic utility of a setae extract, clinical picture and associated risk factors.

PubMed

Vega, José María; Moneo, Ignacio; García-Ortiz, José Carlos; González-Muñoz, Miguel; Ruiz, Carmen; Rodríguez-Mahillo, Ana Isabel; Roques, Alain; Vega, Jesús

2014-01-01

Setae from Thaumetopoea pityocampa larvae (the pine processionary moth or PPM) can induce hypersensitivity reactions, but their clinical role in IgE-mediated responses is still subject to discussion. The aim of this study was to evaluate a setae extract for in vivo and in vitro diagnosis in nonhospitalized patients with reactions to PPM. Forty-eight adult patients presenting with PPM cutaneous reactions were studied by skin prick test (SPT) and specific IgE using setae and whole larval (WL) extracts. Biological standardized extracts were used for skin tests. A total of 47.9% patients had a positive SPT for PPM (70% to both extracts, 17% only to the WL extract and 13% only to the setae extract). IgE immunoblotting detected several reactive bands in 91% of the SPT-positive cases. In multivariate analysis, male sex, immediate latency (<1 h) and duration of skin symptoms (<24 h) were independent predictors of a positive SPT. IgE sensitization to PPM was found in 48% of the study patients, which was associated with immediate reactions and evanescent cutaneous lesions. Most of these patients reacted to both WL and setae extracts, but some reacted to only one of them. According to our data, skin and in vitro tests to PPM should be performed using both extracts. © 2015 S. Karger AG, Basel.

Blood Interferon Signatures Putatively Link Lack of Protection Conferred by the RTS,S Recombinant Malaria Vaccine to an Antigen-specific IgE Response

PubMed Central

Rinchai, Darawan; Presnell, Scott; Vidal, Marta; Dutta, Sheetij; Chauhan, Virander; Cavanagh, David; Moncunill, Gemma; Dobaño, Carlota; Chaussabel, Damien

2017-01-01

Malaria remains a major cause of mortality and morbidity worldwide. Progress has been made in recent years with the development of vaccines that could pave the way towards protection of hundreds of millions of exposed individuals. Here we used a modular repertoire approach to re-analyze a publically available microarray blood transcriptome dataset monitoring the response to malaria vaccination. We report the seminal identification of interferon signatures in the blood of subjects on days 1, 3 and 14 following administration of the third dose of the RTS,S recombinant malaria vaccine. These signatures at day 1 correlate with protection, and at days 3 and 14 to susceptibility to subsequent challenge of study subjects with live parasites. In addition we putatively link the decreased abundance of interferon-inducible transcripts observed at days 3 and 14 post-vaccination with the elicitation of an antigen-specific IgE response in a subset of vaccine recipients that failed to be protected by the RTS,S vaccine. Furthermore, profiling of antigen-specific levels of IgE in a Mozambican cohort of malaria-exposed children vaccinated with RTS,S identified an association between elevated baseline IgE levels and subsequent development of naturally acquired malaria infection during follow up. Taken together these findings warrant further investigation of the role of antigen-specific IgE in conferring susceptibility to malaria infection. PMID:28883910

Ovomucoid (Gal d 1) specific IgE detected by microarray system predict tolerability to boiled hen's egg and an increased risk to progress to multiple environmental allergen sensitisation.

PubMed

Alessandri, C; Zennaro, D; Scala, E; Ferrara, R; Bernardi, M Livia; Santoro, M; Palazzo, P; Mari, A

2012-03-01

Egg allergy is a very common finding in early childhood. Detecting hen's egg (HE) allergy outgrowing and reintroduction of food containing egg is a task for the allergist. We sought to evaluate the suitability of boiled egg food challenge compared with IgE to allergenic molecules from HE white using a microarray system. Sixty-eight children referring to our centre by the family paediatricians for a suspected egg allergy were enrolled. Patients underwent double-blind, placebo-controlled food challenge with boiled and raw eggs. Challenge outcomes were compared with skin tests performed using egg white and yolk commercial extracts, to prick-prick test with boiled and raw egg white and yolk, total IgE, egg white specific IgE detected using ImmunoCAP and IgE to egg allergens available on the immunosolid phase allergen chip (ISAC) 103 microarray. Nineteen subjects (28%) were reactive to both raw and boiled egg, 14 (20.5%) to raw egg only and 35 (51.4%) tolerated both boiled and raw egg. Efficiency analysis was carried out using both raw and boiled egg challenges as gold standard. Forty four of 47 Gal d 1 negative patients tolerated boiled egg (94%). Conversely, 20 of 21 Gal d 1 positive patients reacted to raw egg (95%). None of the other tests was able to discriminate patients' response to HE challenge. Furthermore, Gal d 1 positivity seems to lead to broader environmental allergen IgE sensitization. The Gal d 1 IgE reactivity appears to be a very good predictor of HE clinical allergy. Gal d 1 positive children have a high frequency of HE allergy, whereas Gal d 1 negative children have a high frequency of tolerance to boiled egg. Multiple specific IgE detection by means of ISAC improves the diagnostic approach in HE allergic children, disclosing other food and inhalant allergic sensitizations, anyhow requiring a comprehensive clinical evaluation. © 2011 Blackwell Publishing Ltd.

Correlations Between Allergen-Specific IgE Serum Levels in Patients With Ocular Allergy.

PubMed

Polido, Júlia Gomes Fernandes; Cabral, Thiago; Perini, Paula de Resende Campos; Fernandes, Maria de Fátima Marcelos; de Freitas, Denise; dos Santos Araújo, Maria Emília Xavier; Serracarbassa, Pedro Durães

2015-09-01

To evaluate ocular allergies in patients at the Hospital do Servidor Publico Estadual de Sao Paulo (HSPE) and the correlations with serum allergen-specific immunoglobulin E levels. We performed a longitudinal study of patients with ocular allergies who were treated at the Cornea and Immunology and Allergy Department. Patients underwent an ophthalmologic examination to identify their primary presenting signs and symptoms. The allergy types were divided into 4 groups. We conducted the following laboratory tests and measurements: blood count, eosinophil count, total serum IgE, and specific IgE. Among 61 patients, 16 (26.2%) had a clinical diagnosis of seasonal allergic conjunctivitis, 23 (37.7%) had perennial allergic conjunctivitis, 19 (31.1%) had vernal keratoconjunctivitis, and 3 (4.9%) had atopic keratoconjunctivitis. Mixed dust mites were positive in 94.9% of patients. Dermatophagoides pteronyssinus (dp) and Dermatophagoides farinae (df) antigens were positive in 93.2% of patients followed by Blattella germanica, Blomia tropicalis, and mixed animal epithelia (81%, 75.9%, and 25.8%, respectively). Perennial allergic conjunctivitis was the most prevalent disorder and demonstrated higher positivity in class V/VI for specific antigens (mixed dust mites, dp, and df), indicating high antigenicity. Dust mites, D. pteronyssinus, D. farinae, B. germanica, and B. tropicalis were the primary triggers of the studied ocular allergies.

Interleukin-7 (IL-7) enhances class switching to IgE and IgG4 in the presence of T cells via IL-9 and sCD23.

PubMed

Jeannin, P; Delneste, Y; Lecoanet-Henchoz, S; Gretener, D; Bonnefoy, J Y

1998-02-15

Interleukin-7 (IL-7) is a B-cell growth factor produced by both bone marrow stroma cells and follicular dendritic cells (FDCs) located in primary lymphoid follicles and germinal centers. In this study, we have evaluated the role of IL-7 on human Ig class switching. IL-7 was added to peripheral blood mononuclear cells (PBMCs) or tonsillar B cells in the absence or presence of IL-4 and/or anti-CD40 monoclonal antibody (MoAb). Alone, IL-7 did not affect Ig production by PBMCs or by anti-CD40 MoAb-stimulated B cells. Rather, IL-7 potentiated IL-4-induced IgE and IgG4 production by PBMCs. In parallel, IgG3 production was also enhanced but to a lesser extent, whereas the production of the other isotypes was unaltered. The activity of IL-2, IL-9, or IL-15, which share usage of the common gamma chain for signaling, was also assessed. IL-9, like IL-7, potentiated mainly IgE and IgG4 production by IL-4-stimulated PBMCs. IL-15, in contrast, was ineffective, whereas IL-2 enhanced the production of all isotypes. More precisely, IL-7 potentiation of IgE and IgG4 production required the presence of T cells and was accompanied by an increase of the expression of two soluble molecules favoring preferentially IgE and IgG4 synthesis: CD23 (sCD23) and IL-9. Moreover, neutralizing anti-CD23 and anti-IL-9 antibodies partly inhibited the increase of IgE synthesis induced by IL-7. Thus, IL-7 produced locally in the germinal centers by FDCs may interact with T cells and potentiate human IgE and IgG4 switching by favoring IL-9 and sCD23 production.

No effect of interleukin-2 on IgE levels given in addition to antiretroviral therapy in HIV-infected adults with CD4 >300 cells/mm3.

PubMed

Ananworanich, Jintanat; Chantaphakul, Hiroshi; Teeratakulpisarn, Somsong; Siangphoe, Umaporn; Ubolyam, Sasiwimol; Chuenyam, Theshinee; Ungsedhaphan, Chaiwat; Lange, Joep; Cooper, David; Phanuphak, Praphan; Ruxrungtham, Kiat

2005-03-01

HIV-infected patients may have frequent atopy caused by an imbalance of Th1 and Th2 cytokines. The objective of the present study was to investigate whether IL-2 given in addition to antiretrovirals (ARV) would result in lower IgE levels and less allergic symptoms. Patients naive to IL-2 (n=28) began IL-2 plus ARV and were followed for 12 months. IgE, eosinophil and CD4 counts, HIV RNA, symptom scoring, PFT and skin prick test (SPT) were performed. It was found that the baseline median CD4 and IgE were 386.5 cells/mm3 and 63.5 IU/ml, respectively. Four patients had allergic rhinitis (AR) and 61% had a positive SPT to at least 1 antigen. At month 12, patients had higher CD4 counts (p < 0.001) compared to the baseline; however, there were no differences in IgE levels, allergic symptom scores or HIV RNA. The eosinophil count was higher after IL-2 administration. It was concluded that IL-2 plus ARV resulted in higher CD4 counts but had no effect on atopy.

Allergy to fish collagen: Thermostability of collagen and IgE reactivity of patients' sera with extracts of 11 species of bony and cartilaginous fish.

PubMed

Kobayashi, Yukihiro; Kuriyama, Takuma; Nakagawara, Ryoko; Aihara, Michiko; Hamada-Sato, Naoko

2016-10-01

Parvalbumin was identified as a major fish allergen, and has been well investigated. Collagen was identified as a second allergen; however, its allergenic properties remain uncharacterized. Although fish is an important staple in coastal countries, its thermostability is unknown. Therefore, we aimed to determine the thermostability of fish collagen as an allergen. Meat of seven bony and four cartilaginous fishes was heated at various temperatures and times, and extracts were analyzed using SDS-PAGE, IgE-ELISA, and SPTs. Collagen was dissolved from heated meat of Pacific mackerel into a crude extract. Collagen in the extracts was degraded at a high heating load-140 °C (10 min) or 100 °C (320 min). However, ELISA revealed the IgE reactivities of patients' sera with the extracts were unchanged even after heating the samples. Patients strongly reacted to extract proteins of other bony fish, which were detected by patients' IgE even after heating at 100 °C (320 min). In contrast, reactivities of the extracts of cartilaginous fish were lower than those of bony fish. SPTs in one patient revealed that all bony and cartilaginous fish extracts prepared from heated meat elicited allergic reactions. The IgE reactivity of patients' sera to fish collagen in extracts was retained even when fish meat was treated by a high heating load. As for the fish collagen, the IgE reactivities to cartilaginous fish were lower than that to bony fish. Reducing IgE reactivity to fish meat using heat is difficult, and other modalities will be required to produce hypoallergenic fish meat. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Development of an in vitro model system for studying the interaction of Equus caballus IgE with its high-affinity receptor FcεRI.

PubMed

Sabban, Sari; Ye, Hongtu; Helm, Birgit

2014-11-01

The interaction of IgE with its high-affinity Fc receptor (FcεRI) followed by an antigenic challenge is the principal pathway in IgE mediated allergic reactions. As a consequence of the high affinity binding between IgE and FcεRI, along with the continuous production of IgE by B cells, allergies usually persist throughout life, with currently no permanent cure available. Horses, especially race horses, which are commonly inbred, are a species of mammals that are very prone to the development of hypersensitivity responses, which can seriously affect their performance. Physiological responses to allergic sensitization in horses mirror that observed in humans and dogs. In this paper we describe the development of an in situ assay system for the quantitative assessment of the release of mediators of the allergic response pertaining to the equine system. To this end, the gene encoding equine FcεRIα was transfected into and expressed onto the surface of parental Rat Basophil Leukemia (RBL-2H3.1) cells. The gene product of the transfected equine α-chain formed a functional receptor complex with the endogenous rat β- and γ-chains. The resultant assay system facilitated an assessment of the quantity of mediator secreted from equine FcεRIα transfected RBL-2H3.1 cells following sensitization with equine IgE and antigenic challenge using β-hexosaminidase release as a readout. Mediator release peaked at 36.68% ± 4.88% at 100 ng ml(-1) of antigen. This assay was modified from previous assays used to study human and canine allergic responses. We have also shown that this type of assay system has multiple applications for the development of diagnostic tools and the safety assessment of potential therapeutic intervention strategies in allergic disease.

Development of an in vitro model system for studying the interaction of Equus caballus IgE with its high-affinity receptor FcεRI

PubMed Central

Sabban, Sari; Ye, Hongtu; Helm, Birgit

2014-01-01

The interaction of IgE with its high-affinity Fc receptor (FcεRI) followed by an antigenic challenge is the principal pathway in IgE mediated allergic reactions. As a consequence of the high affinity binding between IgE and FcεRI, along with the continuous production of IgE by B cells, allergies usually persist throughout life, with currently no permanent cure available. Horses, especially race horses, which are commonly inbred, are a species of mammals that are very prone to the development of hypersensitivity responses, which can seriously affect their performance. Physiological responses to allergic sensitization in horses mirror that observed in humans and dogs. In this paper we describe the development of an in situ assay system for the quantitative assessment of the release of mediators of the allergic response pertaining to the equine system. To this end, the gene encoding equine FcεRIα was transfected into and expressed onto the surface of parental Rat Basophil Leukemia (RBL-2H3.1) cells. The gene product of the transfected equine α-chain formed a functional receptor complex with the endogenous rat β- and γ-chains 1. The resultant assay system facilitated an assessment of the quantity of mediator secreted from equine FcεRIα transfected RBL-2H3.1 cells following sensitization with equine IgE and antigenic challenge using β-hexosaminidase release as a readout 2, 3. Mediator release peaked at 36.68% ± 4.88% at 100 ng ml-1 of antigen. This assay was modified from previous assays used to study human and canine allergic responses 4, 5. We have also shown that this type of assay system has multiple applications for the development of diagnostic tools and the safety assessment of potential therapeutic intervention strategies in allergic disease 6, 2, 3. PMID:25406512

Vig r 6, the cytokinin-specific binding protein from mung bean (Vigna radiata) sprouts, cross-reacts with Bet v 1-related allergens and binds IgE from birch pollen allergic patients’ sera

PubMed Central

Guhsl, Eva Elisabeth; Hofstetter, Gerlinde; Hemmer, Wolfgang; Ebner, Christof; Vieths, Stefan; Vogel, Lothar; Breiteneder, Heimo; Radauer, Christian

2014-01-01

Scope Birch pollen associated allergy to mung bean sprouts is caused by cross-reactivity between the birch pollen allergen Bet v 1 and the mung bean allergen Vig r 1. We aimed to determine the allergenicity of the cytokinin-specific binding protein from mung bean (Vig r 6), another allergen related to Bet v 1 with only 31% sequence identity. Methods and results Bet v 1, Gly m 4, Vig r 1, and Vig r 6 were produced in Escherichia coli. In an ELISA, 73 and 32% of Bet v 1-sensitized birch-allergic patients’ sera (n = 60) showed IgE binding to Vig r 1 and Vig r 6, respectively. Of 19 patients who reported allergic reactions or had positive prick-to-prick tests to mung bean sprouts, 79% showed IgE binding to Vig r 1 and 63% showed IgE binding to Vig r 6. Bet v 1 completely inhibited IgE binding to both mung bean allergens. Vig r 6 showed partial cross-reactivity with Vig r 1 and activated basophils sensitized with mung bean allergic patients’ sera. Conclusion We demonstrated IgE cross-reactivity despite low sequence identity between Vig r 6 and other Bet v 1-related allergens. Thus, IgE binding to Vig r 6 may contribute to birch pollinosis-associated mung bean sprout allergy. PMID:23996905

Comparisons of Serum Total IgE, IgG, and IgG1 Levels in Patients with and without Echinococcosis-Induced Anaphylactic Shock

PubMed Central

Li, Yimei; Zheng, Hong; Gu, Meilin; Cao, Xinghua; Wen, Hao; Liu, Zaoling; Liu, Tao

2012-01-01

We investigated serum total immunoglobulin E (IgE), IgG, and IgG1 levels in patients with and without echinococcosis-induced anaphylactic shock. This was a case-control study of 11 patients with echinococcosis-induced anaphylactic shock and 22 echinococcosis patients with cyst rupture but without anaphylactic shock. Blood was collected before surgery (T0), at the time of cyst rupture (T1), and shock (Tx), 1 h (T2), 1 day (T3), and 1 week (T4) after cyst rupture. Serum IgE, IgG, and IgG1 were determined by enzyme-linked immunosorbent assay. Serum IgE, IgG, and IgG1 levels were significantly higher in patients who developed anaphylactic shock at all time points. Increased pre-surgical IgG and IgG1 levels were identified to be a significant risk factors for developing anaphylactic shock. The results showed that a serum IgG concentration of 312.25 μg/mL could be used as a cut-off point to predict whether an echinococcosis patient would develop anaphylactic shock. PMID:22764299

The Immunomodulating Effect of a Diet Consisting of Green Vegetables, Beef, Whole Milk and Full-Fat Butter for Children with Non-Specific Elevated IgE.

PubMed

van der Gaag, Ellen Jose; Forbes, Kristina

2014-01-01

Non-specific elevated IgE and allergies are common in children, and their prevalence is increasing. Dietary changes could be an explanation for this increase. Zinc, iron, vitamins A, C and E, and polyunsaturated fatty acids all play possible roles in the etiology and possible treatment of allergies due to their numerous immunomodulating properties. To investigate the immunomodulating effect of recommending a nutrient-rich diet consisting of green vegetables, beef, whole milk and full-fat butter. We conducted a case-controlled, non-randomized, retrospective study. Children between the ages of 1 and 18 years with non-specific elevated IgE were included. Baseline and follow-up measurements of serum total IgE and clinical outcomes were retrospectively collected and compared for 49 children who received the dietary advice (to eat green vegetables, beef, whole milk and full-fat butter) and 56 children who did not. The initial analysis showed a significantly greater decrease in IgE in the intervention group compared to the control group; a 9.2 kU/l versus a 0.1 kU/l decrease, respectively (P = 0.02). When supplement (vitamin D) use was taken into account, however, no significant difference was produced by the dietary effect alone (unstandardized coefficient = 71.3 kU/l, P = 0.16). 53.2 % of participants in the intervention group reported considerable improvement in symptoms versus 28.6 % in the control group (P < 0.001). Overall, the effects of nutrients and vitamins on the decrease in IgE are promising. The separate contributions of dietary advice and/or supplements need to be investigated in the future.

Increasing Total Serum IgE, Allergic Bronchopulmonary Aspergillosis, and Lung Function in Cystic Fibrosis.

PubMed

Gothe, Florian; Kappler, Matthias; Griese, Matthias

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity disorder contributing to lung disease in cystic fibrosis (CF) and challenging to diagnose. This study analyzed the predictive value of increasing total IgE (t-IgE) levels in a CF cohort alongside with clinical and serologic data. A total of 387 children and young adults were followed from 2000 to 2006 and retrospectively classified into 6 groups. Patients with t-IgE levels < 95th percentile and without specific Aspergillus fumigatus (Af)-IgE were classified as "Naïve," those with Af-specific IgE (Af-sIgE) as "Sensitized." Patients with elevated t-IgE at entrance and Af-sIgE were labeled "Former ABPA," and those without, as "High t-IgE." Patients whose t-IgE values started normal and exceeded the 95th percentile during the study were labeled either "ABPA at risk" if Af-sIgE-positive or "Rising t-IgE" if not. Courses of t-IgE over time were divided into episodes with increasing IgE (ΔIgE) and related to pulmonary outcome. A total of 125 patients were classified Naïve (32%), 64 Sensitized (17%), 49 ABPA at risk (13%), 32 Rising t-IgE (8%), 102 Former ABPA (26%), and 15 High t-IgE (4%). A total of 874 ΔIgE episodes were accompanied by forced expiratory volume in 1 second (FEV 1 ) declines (r = -0.21, P < .0001). Steroid treatment of severest ΔIgE episodes resulted in improved long-term pulmonary outcomes (P < .01). This FEV 1 preservation effect was only detectable if t-IgE levels at least doubled within 3 months and exceeded the 95th age-specific percentile (P < .05). ΔIgE obtained from the course of t-IgE levels may be helpful in diagnosing treatment requiring ABPA and predicts the effect of systemic steroid treatment on pulmonary outcome. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Comparison of the results of intradermal test reactivity and serum allergen-specific IgE measurement for Malassezia pachydermatis in atopic dogs.

PubMed

Oldenhoff, Willam E; Frank, Glenn R; DeBoer, Douglas J

2014-12-01

Malassezia pachydermatis is part of the normal flora of canine skin. Malassezia hypersensitivity is recognized as a trigger for clinical signs of atopic dermatitis (AD) in some dogs. Determinations of Malassezia hypersensitivity are often made with intradermal testing (IDT), which may have limited availability in a first-opinion veterinary practice. The purpose of this study was to compare immediate IDT reactivity to M. pachydermatis with results of an enzyme-linked immunosorbent assay (ELISA) designed to detect anti-Malassezia IgE. Eighty-four dogs with a clinical diagnosis of AD. Multi-allergen IDT was performed on all dogs. Serum testing for allergen-specific IgE against a panel of common environmental allergens and M. pachydermatis was performed by ELISA using the FcεRIα receptor fragment as a detection reagent, with results reported as adjusted optical density (OD). A receiver operating characteristic (ROC) curve was used to analyse the results of the two tests. The median adjusted OD of the anti-Malassezia IgE ELISA for dogs reactive and nonreactive to M. pachydermatis on IDT was 0.137 and 0.024, respectively. Analysis of the ROC curve suggested a cut-off point for the anti-Malassezia ELISA that yielded a sensitivity of 77.0% and a specificity of 89% relative to IDT results. Substantial agreement was demonstrated between IDT reactivity and anti-Malassezia IgE as detected by the FcεRIα receptor reagent. Although correlation with a clinical diagnosis of Malassezia dermatitis was not attempted in this study, the results indicate that the ELISA may be used to demonstrate the presence of immediate-type Malassezia hypersensitivity in dogs with AD. © 2014 ESVD and ACVD.

Evaluation of a commercial IgE ELISA in comparison with IgA and IgM ELISAs, IgG avidity assay and complement fixation for the diagnosis of acute toxoplasmosis.

PubMed

Kodym, P; Machala, L; Rohácová, H; Sirocká, B; Malý, M

2007-01-01

A panel of sera from patients with known case histories representative of acute toxoplasmosis (primarily lymphadenopathy, n = 106), latent toxoplasmosis (asymptomatic, n = 368) and negative samples (n = 54) was used to evaluate the capacity of five serological tests to differentiate among patients with acute or latent toxoplasmosis and non-infected individuals. Positive IgA, IgE and IgM ELISA results and low IgG avidity and complement fixation test (CFT) titres of >or=256 were considered to be indicative of acute toxoplasmosis. The most sensitive methods were IgM ELISA (98.1%) and CFT (97.1%), albeit with low specificity (65.0% and 64.5%, respectively) and positive predictive values (43.3% and 42.7%, respectively). IgG avidity assay and IgE ELISA had the highest specificity (97.7% and 91.7%, respectively) and the highest positive predictive values (89.4% and 75.6%, respectively). The best association between serological results and clinical findings was obtained with IgE ELISA (86%, as expressed via Youden's index). In a subset of 259 samples categorised by the period between the onset of clinical symptoms and sampling, >50% of patients had enlarged lymph nodes for <4 months, despite a broad range of differences. However, IgM remained positive for 12-18 months, IgA for 6-9 months and IgE for 4-6 months. IgG avidity remained low for a maximum of 4 months, after which avidity increased despite the persistence of enlarged lymph nodes and a positive IgE assay. Detection of IgE appears to be a highly specific test for confirming the acute nature of Toxoplasma infections that have been detected by other sensitive methods.

Effects of geohelminth infection and age on the associations between allergen-specific IgE, skin test reactivity and wheeze: a case-control study

PubMed Central

Moncayo, A-L; Vaca, M; Oviedo, G; Workman, L J; Chico, M E; Platts-Mills, T A E; Rodrigues, L C; Barreto, M L; Cooper, P J

2013-01-01

Background Most childhood asthma in poor populations in Latin America is not associated with aeroallergen sensitization, an observation that could be explained by the attenuation of atopy by chronic helminth infections or effects of age. Objective To explore the effects of geohelminth infections and age on atopy, wheeze, and the association between atopy and wheeze. Methods A case-control study was done in 376 subjects (149 cases and 227 controls) aged 7–19 years living in rural communities in Ecuador. Wheeze cases, identified from a large cross-sectional survey, had recent wheeze and controls were a random sample of those without wheeze. Atopy was measured by the presence of allergen-specific IgE (asIgE) and skin prick test (SPT) responses to house dust mite and cockroach. Geohelminth infections were measured in stools and anti-Ascaris IgE in plasma. Results The fraction of recent wheeze attributable to anti-Ascaris IgE was 45.9%, while those for SPT and asIgE were 10.0% and 10.5% respectively. The association between atopy and wheeze was greater in adolescents than children. Although Anti-Ascaris IgE was strongly associated with wheeze (adj. OR 2.24 (95% CI 1.33–3.78, P = 0.003) and with asIgE (adj. OR 5.34, 95% CI 2.49–11.45, P < 0.001), the association with wheeze was independent of asIgE. There was some evidence that the association between atopy and wheeze was greater in uninfected subjects compared with those with active geohelminth infections. Conclusions and clinical relevance Atopy to house dust mite and cockroach explained few wheeze cases in our study population, while the presence of anti-Ascaris IgE was an important risk factor. Our data provided only limited evidence that active geohelminth infections attenuated the association between atopy and wheeze in endemic areas or that age modified this association. The role of allergic sensitization to Ascaris in the development of wheeze, independent of atopy, requires further investigation. PMID

Vig r 6, the cytokinin-specific binding protein from mung bean (Vigna radiata) sprouts, cross-reacts with Bet v 1-related allergens and binds IgE from birch pollen allergic patients' sera.

PubMed

Guhsl, Eva Elisabeth; Hofstetter, Gerlinde; Hemmer, Wolfgang; Ebner, Christof; Vieths, Stefan; Vogel, Lothar; Breiteneder, Heimo; Radauer, Christian

2014-03-01

Birch pollen associated allergy to mung bean sprouts is caused by cross-reactivity between the birch pollen allergen Bet v 1 and the mung bean allergen Vig r 1. We aimed to determine the allergenicity of the cytokinin-specific binding protein from mung bean (Vig r 6), another allergen related to Bet v 1 with only 31% sequence identity. Bet v 1, Gly m 4, Vig r 1, and Vig r 6 were produced in Escherichia coli. In an ELISA, 73 and 32% of Bet v 1-sensitized birch-allergic patients' sera (n = 60) showed IgE binding to Vig r 1 and Vig r 6, respectively. Of 19 patients who reported allergic reactions or had positive prick-to-prick tests to mung bean sprouts, 79% showed IgE binding to Vig r 1 and 63% showed IgE binding to Vig r 6. Bet v 1 completely inhibited IgE binding to both mung bean allergens. Vig r 6 showed partial cross-reactivity with Vig r 1 and activated basophils sensitized with mung bean allergic patients' sera. We demonstrated IgE cross-reactivity despite low sequence identity between Vig r 6 and other Bet v 1-related allergens. Thus, IgE binding to Vig r 6 may contribute to birch pollinosis-associated mung bean sprout allergy. © 2013 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Sensitization rates of causative allergens for dogs with atopic dermatitis: detection of canine allergen-specific IgE

PubMed Central

Kang, Min-Hee; Kim, Ha-Jung; Jang, Hye-Jin

2014-01-01

Allergen-specific IgE serology tests became commercially available in the 1980s. Since then these tests have been widely used to diagnose and treat allergic skin diseases. However, the relationship between a positive reaction and disease occurrence has been controversial. The purpose of this study was to evaluate allergens using a serologic allergy test in dogs with atopic dermatitis (AD). Dogs clinically diagnosed with AD (n=101) were tested using an allergen-specific IgE immunoassay. Among the total 92 environmental and food allergens, house dust and house dust mites were the most common. Several allergens including airborne pollens and molds produced positive reactions, and which was considered increasing allergens relating to the climate changes. The presence of antibodies against staphylococci and Malassezia in cases of canine AD was warranted in this study. Additionally, strong (chicken, turkey, brown rice, brewer's yeast, and soybean) and weakly (rabbit, vension, duck, and tuna) positive reactions to food allergens could be used for avoidance and limited-allergen trials. PMID:24962408

Sensitization rates of causative allergens for dogs with atopic dermatitis: detection of canine allergen-specific IgE.

PubMed

Kang, Min-Hee; Kim, Ha-Jung; Jang, Hye-Jin; Park, Hee-Myung

2014-12-01

Allergen-specific IgE serology tests became commercially available in the 1980s. Since then these tests have been widely used to diagnose and treat allergic skin diseases. However, the relationship between a positive reaction and disease occurrence has been controversial. The purpose of this study was to evaluate allergens using a serologic allergy test in dogs with atopic dermatitis (AD). Dogs clinically diagnosed with AD (n = 101) were tested using an allergen-specific IgE immunoassay. Among the total 92 environmental and food allergens, house dust and house dust mites were the most common. Several allergens including airborne pollens and molds produced positive reactions, and which was considered increasing allergens relating to the climate changes. The presence of antibodies against staphylococci and Malassezia in cases of canine AD was warranted in this study. Additionally, strong (chicken, turkey, brown rice, brewer's yeast, and soybean) and weakly (rabbit, vension, duck, and tuna) positive reactions to food allergens could be used for avoidance and limited-allergen trials.

Chickenpox in childhood is associated with decreased atopic disorders, IgE, allergic sensitization, and leukocyte subsets.

PubMed

Silverberg, Jonathan I; Kleiman, Edward; Silverberg, Nanette B; Durkin, Helen G; Joks, Rauno; Smith-Norowitz, Tamar A

2012-02-01

Wild-type varicella zoster infection (WTVZV) up to 8 yr of age has been shown to protect against atopic dermatitis (AD) and asthma. We sought to determine whether WTVZV in childhood protects against atopic disorders, allergic sensitization or decreases serum Immunoglobulin E (IgE) levels. We conducted a retrospective, practice-based study of outpatient pediatric practices in NY. One hundred children with WTVZV up to 8 yr of age and 323 children who received varicella vaccine (VV) were randomly selected. WTVZV up to 8 yr of age is associated with decreased odds of subsequent asthma (exact logistic regression; OR = 0.12, 95% CI = 0.03-0.57, p = 0.003), allergic rhinoconjunctivitis (OR = 0.16, 95% CI = 0.05-0.49, p = 0.0003), and AD (OR = 0.57, 95% CI = 0.33-0.96, p = 0.02), but not food allergies (p = 0.78); decreased total serum IgE levels [mixed linear model, LSM (95% CI): 129.09 (33.22-501.63) vs. 334.21 (102.38-1091.04) IU/ml; p = 0.02] remained significant at all time intervals after WTVZV (<5, 5-10, and >10) compared with VV (p = 0.003-0.03). WTVZV was associated with decreased allergic sensitization (logistic regression, OR = 0.11, 95% CI = 0.03-0.38, p = 0.0004). WTVZV is also associated with persistently decreased numbers of peripheral blood lymphocytes (p < 0.0001) for up to 12 yr (p = 0.0003-0.047), monocytes (p = 0.002) for up to 16 yr (p < 0.001) and basophils at ages 4-6, 10-12, and 14-16 (p < 0.03). WTVZV up to 8 yr of age protects against atopic disorders, which is likely mediated by suppression of IgE production and allergic sensitization, as well as altered leukocyte distributions. © 2011 John Wiley & Sons A/S.

Role of specific IgE to β-lactoglobulin in the gastrointestinal phenotype of cow's milk allergy.

PubMed

Poza-Guedes, Paloma; Barrios, Yvelise; González-Pérez, Ruperto; Sánchez-Machín, Inmaculada; Franco, Andres; Matheu, Víctor

2016-01-01

The prevalence of many phenotypes of food allergy is increasing. Specific gastrointestinal (GI) phenotype of food allergy (GI allergy) is also increasing but it is difficult to know the prevalence because of many entities. METHODS AND RESULTS: A 1 year retrospective study of pediatric patients complaining exclusively gastrointestinal symptoms after cow's milk consumption and at least one positive specific IgE (sIgE) to cow's milk (CM) proteins (CMP) was done (n = 39). The most prevalent symptom was abdominal cramps in 35 patients (90 %), discomfort or abdominal distention in 30 patients (75 %), diarrhea in 10 patients (25 %) and constipation in 5 patients (12 %). IgA anti-transglutaminase antibodies were absent and lactose intolerance was ruled out in all patients. Average of total IgE on this group was 288 UI/ml. sIgE against β-lactoglobulin was the dominant with an average of 4.14 kU/l. sIgE to casein (CAS), which is the dominant protein in systemic anaphylaxis was 1.74 kU/l; sIgE to α-lactoalbumin, the other whey protein, was 0.83 kU/l and sIgE levels to CM were 0.78 kU/l. The quotient sIgE CAS/sIgE β-lactoglobulin in these patients was always lower than 1. Patients experienced an improvement of their symptoms after a CM free diet. An open oral challenge with CM did mimic their initial symptoms in all patients. However, the open oral challenge with dairy products was well tolerated. Patients with a specific phenotype of GI allergy with CM have specific IgE against β-lactoglobulin, as a dominant sIgE. These patients could beneficiate of a diet with dairy products.

A comparative study of human IgE binding to proteins of a genetically modified (GM) soybean and six non-GM soybeans grown in multiple locations.

PubMed

Lu, Mei; Jin, Yuan; Ballmer-Weber, Barbara; Goodman, Richard E

2018-02-01

Prior to commercialization, genetically modified (GM) crops are evaluated to determine the allergenicity of the newly expressed protein. Some regulators require an evaluation of endogenous allergens in commonly allergenic crops including soybean to determine if genetic transformation increased endogenous allergen concentrations, even asking for IgE testing using sera from individual sensitized subjects. Little is known about the variability of the expression of endogenous allergens among non-GM varieties or under different environmental conditions. We tested IgE binding to endogenous allergenic proteins in an experimental non-commercial GM line, a non-GM near-isoline control, and five non-GM commercial soybean lines replicated at three geographically separated locations. One-dimensional (1D) and two-dimensional (2D) immunoblotting and ELISA were performed using serum or plasma from eleven soybean allergic patients. The results of immunoblots and ELISA showed no significant differences in IgE binding between the GM line and its non-GM near-isoline control. However, some distinct differences in IgE binding patterns were observed among the non-GM commercial soybean lines and between different locations, highlighting the inherent variability in endogenous allergenic proteins. Understanding the potential variability in the levels of endogenous allergens is necessary to establish a standard of acceptance for GM soybeans compared to non-GM soybean events and lines. Copyright © 2018. Published by Elsevier Ltd.

IgG and IgE antibodies to Chironomidae in asthmatic patients.

PubMed Central

Yamashita, N; Ito, K; Nakagawa, T; Haida, M; Okudaira, H; Nakada, S; Miyamoto, T; Shibuya, T; Kamei, K; Sasa, M

1987-01-01

IgG antibodies to Chironomidae and its correlations to radioallergosorbent and skin reactions were examined with the aim of clarifying the relationship between asthma and Chironomidae. The level of specific IgG antibody in asthmatic patients (0.698 +/- 0.034, n = 104) was significantly greater than that in normal subjects (0.367 +/- 0.032, n = 52) (P less than 0.01). The specific IgG level was not correlated to skin reaction, nor to IgE RAST scores. Specific IgG1 and IgG4 levels in asthmatic patients were significantly greater than in control subjects (n = 14) (P less than 0.01). Images Fig. 5 PMID:3652516

Determinants of total and specific IgE in infants with atopic dermatitis. ETAC Study Group. Early Treatment of the Atopic Child.

PubMed

1997-11-01

ETAC (Early Treatment of the Atopic Child), a multi-centre predominantly European study to investigate the potential for cetirizine to prevent the development of asthma in infants with atopic dermatitis has completed enrollment: 817 children have been randomised to 18 months' treatment with either active or placebo and a subsequent 18 months of post-treatment follow-up. Results of the therapeutic effects will not be available for some time, but the study has provided an opportunity to investigate influences on sensitization to allergens in a large cohort of 1-2 years olds with already established atopic dermatitis, resident in different countries and in different environments. The study shows that in infants with atopic dermatitis, raised serum total IgE has significantly different determinants from that a specific allergen sensitization. In infancy, increased total IgE is more affected by factors increasing risk of intercurrent infection and non-specific airway inflammation, such as environmental tobacco smoke exposure (p < 0.001) and the use of gas cookers (p = 0.02). Specific allergen sensitization as represented by detectable IgE antibodies is influenced primarily by allergen exposure. In Sweden, low level exposure to allergens is associated with reduced specific allergen sensitization rates even though the infants already have atopic dermatitis.

Relation between IgG antibodies to foods and IgE antibodies to milk, egg, cat, dog and/or mite in a cross-sectional study.

PubMed

Eysink, P E; De Jong, M H; Bindels, P J; Scharp-Van Der Linden, V T; De Groot, C J; Stapel, S O; Aalberse, R C

1999-05-01

Because IgG antibodies to foods can be detected before IgE antibodies to inhalants, increased levels of IgG antibodies to foods might be used as a predictor of IgE-mediated allergy in initially nonatopic children. To examine the cross-sectional relation between IgG to foods (i.e. mixture of wheat and rice, mixture of soybean and peanut, egg white, cow's milk, meat, orange and potato) and specific IgE to cat, dog, mite, milk and egg white in 1-year-old children. All atopic children (n = 120; 58 with and 62 without eczema) and a random sample of the nonatopic children (n = 144) of the Bokaal study were tested on their IgG response to foods. The IgG results of the food assays were dichotomized high or low using the 66th centile as a cut-off value. Atopic children more often had high IgG levels to foods than nonatopic children. IgG to egg white (OR = 7.50) and mixture of wheat and rice (OR = 4.79) were most strongly associated with positive specific IgE. In a stepwise logistic regression analysis egg white, mixture of wheat and rice, and orange were selected (OR = 3.76, OR = 2.43, and OR = 2.11, respectively). In children without eczema higher levels of IgG to foods were still significantly associated with atopy, which was most prominent for egg white, orange and cow's milk. An increased IgG antibody level to foods, especially to egg white, orange, and mixture of wheat and rice, indicates an increased risk of having IgE to cat, dog, mite, egg and/or milk allergens, even in the noneczematous group. Therefore, in another prospective study we are currently investigating the usefulness of IgG in early identification, i.e. before IgE antibodies can be detected, of children with an increased risk of developing allergic diseases in the future.

Effect of Heat Processing on IgE Reactivity and Cross-Reactivity of Tropomyosin and Other Allergens of Asia-Pacific Mollusc Species: Identification of Novel Sydney Rock Oyster Tropomyosin Sac g 1.

PubMed

Rolland, Jennifer M; Varese, Nirupama P; Abramovitch, Jodie B; Anania, Jessica; Nugraha, Roni; Kamath, Sandip; Hazard, Anita; Lopata, Andreas L; O'Hehir, Robyn E

2018-05-14

Shellfish allergy is an increasing global health priority, frequently affecting adults. Molluscs are an important shellfish group causing food allergy but knowledge of their allergens and cross-reactivity is limited. Optimal diagnosis of mollusc allergy enabling accurate advice on food avoidance is difficult. We characterized allergens of four frequently ingested Asia-Pacific molluscs: Sydney Rock Oyster (Saccostrea glomerata), Blue Mussel (Mytilus edulis), Saucer Scallop (Amusium balloti) and Southern Calamari (Sepioteuthis australis), examining cross-reactivity between species and with Blue Swimmer Crab tropomyosin, Por p 1. IgE ELISA showed that cooking increased IgE reactivity of mollusc extracts and basophil activation confirmed biologically relevant IgE reactivity. Immunoblotting demonstrated strong IgE reactivity of several proteins including one corresponding to heat-stable tropomyosin in all species (37-40 kDa). IgE-reactive Sydney Rock Oyster proteins were identified by mass spectrometry, and the novel major oyster tropomyosin allergen was cloned, sequenced and designated Sac g 1 by the IUIS. Oyster extracts showed highest IgE cross-reactivity with other molluscs, while mussel cross-reactivity was weakest. Inhibition immunoblotting demonstrated high cross-reactivity between tropomyosins of mollusc and crustacean species. These findings inform novel approaches for reliable diagnosis and improved management of mollusc allergy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

AllergoOncology: Generating a canine anti-cancer IgE against the epidermal growth factor receptor (EGFR).

PubMed

Fazekas-Singer, Judit; Singer, Josef; Ilieva, Kristina M; Matz, Miroslawa; Herrmann, Ina; Spillner, Edzard; Karagiannis, Sophia N; Jensen-Jarolim, Erika

2018-05-07

Anti-cancer immunotherapies currently rely on IgG antibodies. In line with the AllergoOncology concept we provide evidence that tumor-specific IgE, alone or combined with IgG, may be superior to IgG treatment alone. The novel can225IgE-λ was made for future studies in dogs as translational model patients. Copyright © 2018. Published by Elsevier Inc.

Mapping of IgE and IgG4 antibody-binding epitopes in Cyn d 1, the major allergen of Bermuda grass pollen.

PubMed

Yuan, Han-Chih; Wu, Keh-Gong; Chen, Chun-Jen; Su, Song-Nan; Shen, Horng-Der; Chen, Yann-Jang; Peng, Ho-Jen

2012-01-01

Bermuda grass pollen (BGP) is an important seasonal aeroallergen worldwide which induces allergic disorders such as allergic rhinitis, conjunctivitis and asthma. Cyn d 1 is the major allergen of BGP. This study is aimed to map human IgE and IgG(4) antibody-binding sequential epitopes on Cyn d 1 by dot immunoblotting. Synthetic peptides (10-mers; 5 overlapping residues) spanning the full length of Cyn d 1 were used for dot immunoblotting to map human IgE and IgG(1-4) antibody-binding regions with sera from BGP-allergic patients. Synthetic peptides with more overlapping residues were used for further mapping. Essential amino acids in each epitope were examined by single amino acid substitution with alanine. Peptides with sequence polymorphism of epitopes of Cyn d 1 were also synthesized to extrapolate their differences in binding capability. Four major IgE-binding epitopes (peptides 15(-1), 21, 33(-2) and 35(+1), corresponding to amino acids 70-79, 101-110, 159-167 and 172-181) and 5 major IgG(4)-binding epitopes (peptides 15(-1), 30(-2), 33(-2), 35(+1) and 39, corresponding to amino acids 70-79, 144-153, 159-167, 172-181 and 192-200) were identified. They are all located on the surface of the simulated Cyn d 1 molecule, and three of them are major epitopes for both IgE and IgG(4). Their critical amino acids were all characterized. Major epitopes for human IgG(1) to IgG(4) are almost identical. This is the first study to map the sequential epitopes for human IgE and IgG(4) subclasses in Cyn d 1. It will be helpful for future development in immunotherapy and diagnosis. Copyright © 2011 S. Karger AG, Basel.

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

PubMed

Tanaka, Akemi; Takeda, Taisuke; Hoshina, Takao; Fukai, Kazuyoshi; Yamano, Tsunekazu

2010-12-01

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.

Levels of house dust mite-specific serum immunoglobulin E (IgE) in different cat populations using a monoclonal based anti-IgE enzyme-linked immunosorbent assay.

PubMed

Bexley, Jennifer; Hogg, Janice E; Hammerberg, Bruce; Halliwell, Richard E W

2009-10-01

Levels of serum immunoglobulin E (IgE) specific for the house dust mites (HDMs) Dermatophagoides farinae (DF) and Dermatophagoides pteronyssinus (DP) in 58 cats with clinical signs suggestive of atopic dermatitis (allergic dermatitis cats), 52 cats with no history of allergic or immunological disease (nonallergic cats) and 26 specific pathogen-free (SPF) cats were measured using a monoclonal anti-IgE enzyme-linked immunosorbent assay. Reactivity to both native and reduced HDM allergens was compared. SPF cats had significantly lower levels of HDM-specific serum IgE than cats with allergic dermatitis and nonallergic cats. The difference in levels of HDM-specific IgE in the serum of cats with allergic dermatitis and nonallergic cats was significant for native DF allergen, but not for native DP allergen or reduced HDM allergens. The results suggest that DF in its native form may be a significant allergen in cats with allergic dermatitis. The clinical relevance of these reactions, however, remains to be proven.

469 Levels of IL-4, INF-&GAMMA; Total IGE and IGG4 in Serum of Allergic Children within Areas of Risk of Lead Exposure in Torreon Coahuila, Mexico

PubMed Central

Chavez Villarreal, Karen Giselle; Hernandez, Jahzeel Avila; Goytia Acevedo, Raquel Concepción; Velazquez, Rocio Meza; Guillen, Mario Rivera; Jurado, Michelle Gomez; García-Arenas, Guadalupe; Maravilla-Domínguez, Aurora

2012-01-01

Background There are precedents to suggest that lead exposure may increase the severity of allergic disease in children. In Torreon Coahuila is known the problem of lead contamination and its association with the body burden in children. The aim of this study was to evaluate clinical and biochemical characteristics of allergic disease in children living in areas at risk of lead exposure. Methods We included children between 6 and 11 years old with clinical diagnosis of allergy, who were attending by allergic consultation in the Center of attention Heavy Metals in Torreon, Coahuila, Mexico. Medical evaluation was performed following the diagnostic criteria described by ARIA, Global Initiative for Asthma and the Hanifin and Rajka criteria for atopic dermatitis. Skin tests were applied to 47 common allergens in the region. Were quantified in serum, the levels of IL-4, IFN-γ and IgG4 by ELISA, total IgE levels by chemiluminescence and lead in blood by spectrophotometry AA. Results We present the results of 33 patients (16 girls/17 boys) aged 8 ± 1.38. The main risk factors for allergy were current animal contact (66.7%), past animal exposure (60.6%) and passive smoking (51.5%). The predominant allergy diseases: rhinitis (97%), conjunctivitis (43.8%) and atopic dermatitis (33.3%). The allergens with the higher prevalence of responses were: thickets (91.2%) and grass (88.2%). The average blood lead level was 4.36 μg/dL ± 2.13 and median total IgE 660 IU/mL. We present the analysis of the levels of cytokines, total IgE and IgG4 according to the types of allergy, severity and frequency of the disease. Conclusions IgE levels according to the type of allergic disease, severity and frequency seem to be related to the balance IL-4/INF g. The IgG4 seems to be positively related to total IgE levels in rhinitis, conjunctivitis and dermatitis and negatively with Asthma and other allergies. No association was found between blood lead levels and total IgE.

Performing IgE serum testing due to bioinformatics matches in the allergenicity assessment of GM crops.

PubMed

Goodman, Richard E

2008-10-01

Proteins introduced into genetically modified (GM) organisms through genetic engineering must be evaluated for their potential to cause allergic disease under various national laws and regulations. The Codex Alimentarius Commission guidance document (2003) calls for testing of serum IgE binding to the introduced protein if the gene was from an allergenic source, or the sequence of the transferred protein has >35% identity in any segment of 80 or more amino acids to a known allergen or shares significant short amino acid identities. The Codex guidance recognized that the assessment will evolve based on new scientific knowledge. Arguably, the current criteria are too conservative as discussed in this paper and they do not provide practical guidance on serum testing. The goals of this paper are: (1) to summarize evidence supporting the level of identity that indicates potential risk of cross-reactivity for those with existing allergies; (2) to provide example bioinformatics results and discuss their interpretation using published examples of proteins expressed in transgenic crops; and (3) to discuss key factors of experimental design and methodology for serum IgE tests to minimize the rate of false negative and false positive identification of potential allergens and cross-reactive proteins.

Timescale Separation of Positive and Negative Signaling Creates History-Dependent Responses to IgE Receptor Stimulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harmon, Brooke; Chylek, Lily A.; Liu, Yanli

The high-affinity receptor for IgE expressed on the surface of mast cells and basophils interacts with antigens, via bound IgE antibody, and triggers secretion of inflammatory mediators that contribute to allergic reactions. To understand how past inputs (memory) influence future inflammatory responses in mast cells, a microfluidic device was used to precisely control exposure of cells to alternating stimulatory and non-stimulatory inputs. We determined that the response to subsequent stimulation depends on the interval of signaling quiescence. For shorter intervals of signaling quiescence, the second response is blunted relative to the first response, whereas longer intervals of quiescence induce anmore » enhanced second response. Through an iterative process of computational modeling and experimental tests, we found that these memory-like phenomena arise from a confluence of rapid, short-lived positive signals driven by the protein tyrosine kinase Syk; slow, long-lived negative signals driven by the lipid phosphatase Ship1; and slower degradation of Ship1 co-factors. This work advances our understanding of mast cell signaling and represents a generalizable approach for investigating the dynamics of signaling systems.« less

Increased levels of IgE and autoreactive, polyreactive IgG in wild rodents: implications for the hygiene hypothesis

USGS Publications Warehouse

Devalapalli, A.P.; Lesher, A.; Shieh, K.; Solow, J.S.; Everett, M.L.; Edala, A.S.; Whitt, P.; Long, Renee R.; Newton, N.; Parker, W.

2006-01-01

To probe the potential role of Th1 versus Th2 reactivity underlying the hygiene hypothesis, intrinsic levels of Th1-associated and Th2-associated antibodies in the serum of wild rodents were compared with that in various strains of laboratory rodents. Studies using rat lung antigens as a target indicated that wild rats have substantially greater levels of autoreactive, polyreactive immunoglobulin G (IgG), but not autoreactive, polyreactive IgM than do laboratory rats, both on a quantitative and qualitative basis. Increased levels of serum IgG and IgE were observed in both wild rats and wild mice relative to their laboratory-raised counterparts, with the effect being most pronounced for IgE levels. Further, wild rats had greater intrinsic levels of both Th1- and Th2-associated IgG subclasses than did lab rats. The habitat (wild versus laboratory raised) had a more substantial impact on immunoglobulin concentration than did age, strain or gender in the animals studied. The presence in wild rodents of increased intrinsic, presumably protective, non-pathogenic responses similar to both autoimmune (autoreactive IgG, Th1-associated) and allergic (IgE, Th2-associated) reactions as well as increased levels of Th1-associated and Th2-associated IgG subclasses points toward a generally increased stimulation of the immune system in these animals rather than a shift in the nature of the immunoreactivity. It is concluded that, at least to the extent that feedback inhibition is a controlling element of immunoreactivity, an overly hygienic environment may affect the threshold of both types of immune responses more so than the balance between the different responses.

Increased levels of IgE and autoreactive, polyreactive IgG in wild rodents: implications for the hygiene hypothesis.

PubMed

Devalapalli, A P; Lesher, A; Shieh, K; Solow, J S; Everett, M L; Edala, A S; Whitt, P; Long, R R; Newton, N; Parker, W

2006-08-01

To probe the potential role of Th1 versus Th2 reactivity underlying the hygiene hypothesis, intrinsic levels of Th1-associated and Th2-associated antibodies in the serum of wild rodents were compared with that in various strains of laboratory rodents. Studies using rat lung antigens as a target indicated that wild rats have substantially greater levels of autoreactive, polyreactive immunoglobulin G (IgG), but not autoreactive, polyreactive IgM than do laboratory rats, both on a quantitative and qualitative basis. Increased levels of serum IgG and IgE were observed in both wild rats and wild mice relative to their laboratory-raised counterparts, with the effect being most pronounced for IgE levels. Further, wild rats had greater intrinsic levels of both Th1- and Th2-associated IgG subclasses than did lab rats. The habitat (wild versus laboratory raised) had a more substantial impact on immunoglobulin concentration than did age, strain or gender in the animals studied. The presence in wild rodents of increased intrinsic, presumably protective, non-pathogenic responses similar to both autoimmune (autoreactive IgG, Th1-associated) and allergic (IgE, Th2-associated) reactions as well as increased levels of Th1-associated and Th2-associated IgG subclasses points toward a generally increased stimulation of the immune system in these animals rather than a shift in the nature of the immunoreactivity. It is concluded that, at least to the extent that feedback inhibition is a controlling element of immunoreactivity, an overly hygienic environment may affect the threshold of both types of immune responses more so than the balance between the different responses.

Epicutaneous sensitization with nematode antigens of fish parasites results in the production of specific IgG and IgE.

PubMed

Fontenelle, G; Knoff, M; Verícimo, M A; São Clemente, S C

2018-07-01

Fish consumption plays an important role in the human diet. Hoplias malabaricus, trahira, is a freshwater fish widely appreciated in several Brazilian states and it is frequently infected by Contracaecum multipapillatum third-instar larvae (L3). The aim of the present study was to evaluate the allergenic potential of the C. multipapillatum L3 crude extract (CECM). BALB/c mice were immunized intraperitoneally (ip) with 10 or 50 μg CECM associated with 2 mg of aluminium hydroxide on days 0, 14 and 48. The determination of specific IgG and IgE antibody levels was done after immunization, and the late immunity was evaluated by the intradermal reaction in the ear pavilion. Epicutaneous sensitization was performed in the dorsal region, with antigenic exposure via a Finn-type chamber, containing 100 μg of chicken ovum albumin (OVA) or 100 μg CECM. After the exposures, the specific antibody levels were determined. In the ip immunization, there was a gradual increase in IgG antibody levels, independent of CECM concentration. In relation to IgE production, it was transitory, and immunization with 10 μg was more efficient than that of 50 μg. The same result was observed in the cellular hypersensitivity reaction. In the case of antigen exposure by the epicutaneous route, it was verified that only CECM was able to induce detectable levels of specific IgG and IgE antibodies. In the present study it was demonstrated that both intraperitoneal immunization and epicutaneous contact with C. multipapillatum larval antigens are potentially capable of inducing allergic sensitization in mice.

Component-resolved microarray analysis of IgE sensitization profiles to Felis catus major allergen molecules in Russian cat-allergic patients.

PubMed

Dolgova, Anna Sergeevna; Sudina, Anna Evgenevna; Cherkashina, Anna Sergeevna; Stukolova, Olga Alekseevna

We aimed to determine the profile of IgE reactivity to three major cat allergens, Fel d 1, Fel d 2 and Fel d 4, in cat-allergic patients in the Moscow region in Russia. sIgE levels to recombinant proteins expressed in Escherichia coli (Fel d 1 and Fel d 4) and to Fel d 2 protein purified from cat serum were measured using a microarray method developed in our laboratory. Sera from 174 anonymous subjects with a positive reaction (≥0.35 IU/mL) to cat dander extract (e1, ImmunoCAP) and 56 negative controls were used for IgE testing. Fel d 1 was recognized by 92.5%, Fel d 2 by 29.9% and Fel d 4 by 39.1% of the tested patient sera. The sensitivity to these three proteins was approximately 98% compared to cat dander extract (correlation coefficient to ImmunoCAP is 0.94 with PPV = 0.99 and NPV = 0.95). These predictive values appeared to be even more statistically significant than the divergence between the ISAC IgE test and the extract-based singleplex ImmunoCAP. The combination of the three investigated proteins (Fel d 1, Fel d 2 and Fel d 4) is suitable for in vitro molecular (serological) diagnosis of cat allergy in this region as a complement to cat dander extract. Moreover, with this method, we found distinction between Fel d 2 and other Feline sIgEs formation.

Repeated Amblyomma testudinarium tick bites are associated with increased galactose-α-1,3-galactose carbohydrate IgE antibody levels: A retrospective cohort study in a single institution.

PubMed

Hashizume, Hideo; Fujiyama, Toshiharu; Umayahara, Takatsune; Kageyama, Reiko; Walls, Andrew F; Satoh, Takahiro

2018-06-01

Alpha-gal syndrome is a hypersensitivity reaction to red meat mediated by IgE antibody specific to galactose-α-1,3-galactose carbohydrate (alpha-gal). Amblyomma tick bites are associated with this condition, but the pathophysiology is not understood. To clarify the mechanism of development of alpha-gal syndrome after tick bites. We compared alpha-gal antibody levels between patients with and without a history of tick bites and examined histologic stainings of tick bite lesions between patients with and without detectable alpha-gal IgE antibody. Patients who had ≥2 tick bites had higher levels of alpha-gal IgE antibody compared with those with only 1 tick bite or healthy individuals. On histologic investigation, greater numbers of basophils and eosinophils, but not mast cells, were observed infiltrating lesions of patients with ≥2 tick bites compared with those with 1 tick bite. Type 2 cytokine-producing T-cell infiltration was predominantly observed in such patients. The study was conducted at a single institution in Japan. In Amblyomma tick bite lesions, basophils; eosinophils; and type 2, cytokine-producing T cells infiltrate the skin and alpha-gal IgE antibodies are produced. These findings provide a potential mechanistic connection between Amblyomma bites and red meat hypersensitivity. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

IgE reactivity to profilin in pollen-sensitized subjects with adverse reactions to banana and pineapple.

PubMed

Reindl, J; Rihs, H P; Scheurer, S; Wangorsch, A; Haustein, D; Vieths, S

2002-06-01

The so-called 'latex-fruit syndrome' is a well-documented phenomenon in cross-reactive allergies. By contrast, there is a lack of information about allergy to exotic fruits in patients with a predominant pollen sensitization. Since the ubiquitous protein profilin has been identified as an allergen in natural rubber latex as well as in pollen-related foods, the aim of this study was to investigate the role of profilin in allergy to certain exotic fruits. Recombinant profilins from banana and pineapple were cloned by a PCR technique after isolation of total RNA using degenerated profilin-specific primers. The unknown 5' ends of copy DNA (cDNA) were identified by rapid amplification of 5'cDNA ends (5'-RACE) and expression in Escherichia coli BL21(DE3) cells. The recombinant profilins were purified by affinity chromatography using poly-(L)-proline as the solid phase. IgE-binding capabilities were characterized by means of immunoblot and Enzyme Allergosorbent Test (EAST). The cross-reactivity to birch pollen profilin and latex profilin was studied by EAST as well as by immunoblot inhibition experiments. Both banana and pineapple profilin were found to consist of 131 amino acid residues with high amino acid sequence identity to known allergenic pollen and food profilins (71-84%). IgE binding to the recombinant profilins was observed in 7/16 sera from subjects with suspected banana allergy (44%) and in 8/19 sera from subjects with suspected pineapple allergy (42%). Inhibition experiments indicated similar IgE reactivity of natural and recombinant allergens. In addition, high cross-reactivity to birch pollen profilin Bet v 2 and latex profilin Hev b 8 was demonstrated by immunoblot inhibition as well as EAST inhibition experiments. Since a high IgE-binding prevalence of about 40% was obtained in both banana and pineapple allergy, we conclude that profilin is an important mediator of IgE cross-reactivity between pollen and exotic fruits. Copyright 2002 S. Karger AG, Basel

Detailed characterization of Act d 12 and Act d 13 from kiwi seeds: implication in IgE cross-reactivity with peanut and tree nuts.

PubMed

Sirvent, S; Cantó, B; Gómez, F; Blanca, N; Cuesta-Herranz, J; Canto, G; Blanca, M; Rodríguez, R; Villalba, M; Palomares, O

2014-11-01

Act d 12 (11S globulin) and Act d 13 (2S albumin) are two novel relevant allergens from kiwi seeds that might be useful to improve the diagnostic sensitivity and the management of kiwifruit-allergic patients. To perform a comprehensive structural and immunological characterization of purified Act d 12 and Act d 13 from kiwi seeds. Sera from 55 well-defined kiwifruit-allergic patients were used. Act d 12 and Act d 13 were purified by chromatographic procedures. Circular dichroism, mass spectrometry, concanavalin A detection, immunoblotting, enzyme-linked immunosorbent assays, basophil activation tests, and IgE-inhibition experiments were used. Act d 12 and Act d 13 were purified from kiwi seeds to homogeneity by combining size-exclusion, ion-exchange, and RP-HPLC chromatographies. Both purified allergens preserve the structural integrity and display typical features of their homologous counterparts from the 11S globulin and 2S albumin protein families, respectively. These allergens are released from kiwi seeds after oral and gastric digestion of whole kiwifruit, demonstrating their bioavailability after ingestion. The allergens retain the capacity to bind serum IgE from kiwifruit-allergic patients, induce IgE cross-linking in effector-circulating basophils, and display in vitro IgE cross-reactivity with homologous counterparts from peanut and tree nuts. Purified Act d 12 and Act d 13 from kiwi seeds are well-defined molecules involved in in vitro IgE cross-reactivity with peanut and tree nuts. Their inclusion in component-resolved diagnosis of kiwifruit allergy might well contribute to improve the diagnostic sensitivity and the management of kiwifruit-allergic patients. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Postmortem serum levels of tryptase and total and specific IgE in fatal asthma.

PubMed

Salkie, M L; Mitchell, I; Revers, C W; Karkhanis, A; Butt, J; Tough, S; Green, F H

1998-01-01

Sera were obtained postmortem from 55 subjects classified into three groups; death due to asthma (FA, n = 21), asthmatic but death not due to asthma (NFA, n = 24) and a nonasthmatic control group (NAC, n = 10). A full autopsy was performed on all cases and a medical history, including details of allergies, was obtained by questionnaire from the next of kin. Grading of asthma severity by either questionnaire or autopsy was comparable (tP = 0.435, p > 0.05) and the mean pathology-grade was significantly higher for the FA group (3.375) compared to the NFA group (2.375), p < 0.05. Tryptase was elevated (> 2.0 micrograms/L) in 21/55 sera (38%) and there was no significant difference between the groups. ROC plots showed that tryptase levels did not discriminate between the FA and NFA groups, even if specimens were collected within 24 hours after death. Total IgE was significantly elevated in the FA group (geometric mean 140.3 kU/L) compared to the other two groups (NFA 30.2 kU/L, NAC 9.4 kU/L), p = 0.05. Fatal asthmatics also had a greater positivity (67%) to a screen for common inhalant allergens than did the other groups (NFA 30%, NAC 20%). Sera with a positive screen were tested against a panel of 10 common aero-allergens. Each sample was then assigned a number (N) and a score (S), dependent on either the number of allergens positive (N) or the total sum of pluses for all allergens (S). Both the N and S values were higher for the FA group (N = 98, S = 264) than the NFA group (N = 52, S = 151) and NAC group (N = 4, S = 8). The ratio (S/N) which gives an index (I) was 2.69, 2.90, and 2.00, respectively. Tryptase was poorly correlated to the total IgE level (r = 0.036); however, mean values for N and S were significantly different (N 6.81, S 4.50, and N 19.25, S 11.5, p < 0.05) for sera with tryptase levels < 2.0 or > or = 2.0 micrograms/L, respectively. We conclude that total and specific IgE may be useful predictors of asthma severity but that postmortem tryptase is

Specific recognition of hydatid cyst antigens by serum IgG, IgE, and IgA using western blot.

PubMed

Sbihi, Y; Janssen, D; Osuna, A

1997-01-01

Diagnosis of hydatid disease in humans relies on the detection of specific antibodies against antigens of the metacestode from Echinococcus granulosus. The specificity and sensitivity of current immunological techniques based on specific serum IgG rely on the way antigens are purified. We used Western immunoblotting to detect specific IgG, IgE, and IgA antibodies in serum from patients with hydatid disease using either crude antigen preparations (total hydatid fluid), purified fractions enriched in Antigens 5 and B, and glycoproteins from hydatid fluid. Depending on whether crude HF or purified antigen fractions were used, IgG and IgE recognized specifically low-to-medium MW bands between 12 and 42 kDa. IgA recognized specifically 110 kDa band in crude hydatid fluid and in the glycoprotein fraction of hydatid fluid, and a 42 kDa band in all antigen samples used. Besides the advantage of detecting specific IgA in crude hydatid fluid, these results offer the possibility of simplifying future immunological tests if specific secretory IgA can be similarly detected.

Contribution of serum IL-4 and IgE to the early prediction of allergic reactions induced by chlorogenic acid.

PubMed

Xiao, Gui Nan; Sun, Qing Ping; Chen, Hao An

2013-01-15

Chlorogenic acid (CA) is one of the active ingredients in some Chinese herbal injections, which may cause allergic reactions in clinic therapy. However, the criterion of test for allergen had not been employed in current Pharmacopeia of United States, European Pharmacopeia, Japanese Pharmacopeia and British Pharmacopeia. In order to find a new way to predict allergic reactions induced by CA earlier, the guinea pigs were sensitized successively by injecting CA intravenously once a day for three times, the results were compared that of Chinese Pharmacopeia by injecting CA intraperitoneally once every other day for three times, serum IL-4 and total IgE were detected by method of enzyme linked immunosorbent assay (ELISA) before guinea pigs were challenged once by injecting the same drug intravenously. The time-effectiveness and dose-effect of allergic reactions induced by CA were also studied. We found that contents of serum IL-4 and total IgE increased significantly before guinea pigs were challenged, either in D8 after intravenous sensitization (1.5 g/l CA, 0.5 ml) or in D14 and D21 after intraperitoneal sensitization (1.5 g/l CA, 0.5 ml), and allergic reactions occurred in all guinea pigs after challenged once by injecting CA (1.5 g/l, 1.0 ml) intravenously. It provides a new way to predict whether CA (or Chinese herbal injections contained CA) can provoke allergic reactions by detecting serum IL-4 and total IgE earlier; the examination period is reduced by 1-2 weeks. It has a good prospect of application in drug emergency test. Copyright © 2012 Elsevier B.V. All rights reserved.

Evaluation of a multiple food specific IgE antibody test compared to parental perception, allergy skin tests and RAST.

PubMed

Adler, B R; Assadullahi, T; Warner, J A; Warner, J O

1991-11-01

This study was set up to evaluate the food panel of a multiple specific IgE antibody assay in 67 atopic asthmatic children by comparing it to the conventional radioallergosorbent test (RAST) and skin-prick tests (SPT) and then comparing the results of these investigations with the parents' perceptions of food related problems. Fifteen food specific IgE antibodies were measured using the multiple chemiluminescence assay (MAST-CLA). IgE antibodies to five of these food allergens were also measured by conventional RAST and SPTs were performed in 43 using 11 standardized food extracts matched to the multiple allergosorbent chemiluminescent assay (MAST-CLA) profile. SPT and MAST-CLA results showed good agreement with one another, range 68.8-96.7% (average 87%), with significant correlation for most allergens tested. MAST-CLA was discrepant with RAST and/or SPTs in 58/210 (27.6%). A questionnaire was sent to the parents to determine their perception of food related symptoms. Sixty-two (92%) questionnaire replies were received, of which 56% reported symptoms with food. The most frequent symptom perceived to be due to food intolerance was behavioural disturbance. The commonest foods implicated were additives (39%), egg (27%), milk (26%), chocolate (23%) and orange (15%). History, SPT, MAST-CLA and RAST were compared for five allergens in 42 patients (210 values). In 14/210 (6.7%), all the tests were negative despite reported symptoms. Conversely in 49/210 (23.3%) at least one test was positive without symptoms. This study did not support a benefit of multipole testing instead of individually selected RASTs or SPTs.(ABSTRACT TRUNCATED AT 250 WORDS)

Microarray evaluation of specific IgE to allergen components in elite athletes.

PubMed

Bonini, M; Marcomini, L; Gramiccioni, C; Tranquilli, C; Melioli, G; Canonica, G W; Bonini, S

2012-12-01

Allergic sensitization and diseases have been reported to have a very high and increasing prevalence in elite athletes. Over 80% of allergic athletes are poly-sensitized. This study aims at evaluating the potential diagnostic added value of a microarray technology (ImmunoCAP ISAC, Phadia AB [at present Thermo Fisher Scientific] Uppsala, Sweden which detects IgE antibodies to specific or cross-reacting allergen components. Seventy-two poly-sensitized athletes according to skin prick test (SPT) with different allergic phenotypes (asthma n = 19; rhino-conjunctivitis n = 20; food allergy and/or oral allergy syndrome n = 13; no clinical symptoms n = 20) and two different control populations (20 poly-sensitized sedentary subjects with respiratory allergy and 20 healthy athletes with negative SPT) were studied for detecting specific IgE (sIgE) both to allergen extracts (ImmunoCAPsIgE) and to allergen components (ImmunoCAP ISAC). ImmunoCAP ISAC detected the presence of sIgE in 90% of poly-sensitized athletes--in 96% with symptoms and in 75% without symptoms--and in 100% of allergic controls. The pattern of positivity towards the 103 components tested differed from subject to subject, even in those with the same sensitization to allergen extract SPT or sIgE. Based on the ISAC results, poly-sensitized athletes were classified into the following prototypical patterns, differently represented in the clinical phenotypes studied (P = 0.03): (1) One single predominant specific allergen positivity; (2) sIgE to two or more non-cross-reacting allergens; (3) sIgE to cross-reacting allergens; and (4) sIgE to components potentially responsible for severe allergic reactions. The ImmunoCAP ISAC represents a useful additional tool for diagnosis and management of poly-sensitized athletes. © 2012 John Wiley & Sons A/S.

Search for a Novel Allergen in Hen's Egg Allergy Using an IgE Immunoblotting Assay.

PubMed

Sogawa, Kazuyuki; Takahashi, Yuria; Shibata, Yui; Satoh, Mamoru; Kodera, Yoshio; Nomura, Fumio; Tanaka, Toshio; Sato, Hironori; Yamaide, Fumiya; Nakano, Taiji; Iwahashi, Kazuhiko; Sugita-Konishi, Yoshiko; Shimada, Akinori; Shimojo, Naoki

2018-04-18

Food allergy is a serious health issue affecting roughly 4% of children, with a substantial effect on quality of life. Chicken egg allergy is frequently observed in infants. Therefore, some of them have to exclude hen's eggs from their daily diet to avoid allergenic symptoms. Hen's egg is composed of 2 soluble parts; one is egg white, which has been characterized as the major source of allergenicity, while the other is egg yolk, which is estimated as a miner source. Only 2 allergens from egg yolk, α-livetin (Gal d 5) and YGP42 (Gal d 6), have been described to date. Sera from 53 patients allergic to hen's eggs and 2 patients allergic to sesame were obtained from the Department of Pediatrics, Chiba University Hospital. The study was performed using SDS-PAGE, IgE immunoblotting, and dot blotting. Seven bands of egg yolk were detected by IgE immunoblotting. Out of these bands, a possible new allergen was further characterized by LC-MS/MS. The 33-kDa band was identified as yolk glycoprotein (YGP40) by LC-MS/MS. A total of 21 of the 53 patients (47%) had YGP40 detected by dot blotting. We identified YGP40 as a new hen's egg yolk allergen and detected 4 sites of YGP40 as linear epitopes. © 2018 S. Karger AG, Basel.

A comparison of skin prick tests, intradermal skin tests, and specific IgE in the diagnosis of mouse allergy.

PubMed

Sharma, Hemant P; Wood, Robert A; Bravo, Andrea R; Matsui, Elizabeth C

2008-04-01

Mouse sensitization is assessed by using skin testing and serum levels of mouse allergen-specific IgE (m-IgE). However, it is unknown whether a positive skin test response or m-IgE result accurately identifies those with clinically relevant mouse sensitization. We sought to compare skin testing and m-IgE measurement in the diagnosis of mouse allergy. Sixty-nine mouse laboratory workers underwent skin prick tests (SPTs), intradermal tests (IDTs), and serum IgE measurements to mouse allergen, followed by nasal challenge to increasing concentrations of mouse allergen. Challenge response was assessed by nasal symptom score. Thirty-eight women and 31 men with a mean age of 30 years were studied. Forty-nine workers reported mouse-related symptoms, of whom 10 had positive m-IgE results and 12 had positive SPT responses. Fifteen had negative SPT responses but positive IDT responses. Positive nasal challenges were observed in 70% of workers with positive m-IgE results, 83% of workers with positive SPT responses, 33% of workers with negative SPT responses/positive IDT responses, and 0% of workers with negative IDT responses. SPTs performed best, having the highest positive and negative predictive values. Among participants with a positive challenge result, those with a positive SPT response or m-IgE result had a significantly lower challenge threshold than those with a positive IDT response (P = .01). Workers with a positive challenge result were more likely to have an increase in nasal eosinophilia after the challenge compared with those with a negative challenge result (P = .03). SPTs perform best in discriminating patients with and without mouse allergy. Mouse-specific IgE and IDTs appear to be less useful than SPTs in the diagnosis of mouse allergy.

Antigen-Conjugated Human IgE Induces Antigen-Specific T Cell Tolerance in a Humanized Mouse Model

PubMed Central

Baravalle, Günther; Greer, Alexandra M.; LaFlam, Taylor N.; Shin, Jeoung-Sook

2015-01-01

Dendritic cells (DCs) play an important role in immune homeostasis through their ability to present Ags at steady state and mediate T cell tolerance. This characteristic renders DCs an attractive therapeutic target for the induction of tolerance against auto-antigens or allergens. Accordingly, Ag-conjugated DC–specific Abs have been proposed to be an excellent vehicle to deliver Ags to DCs for presentation and tolerance induction. However, this approach requires laborious reagent generation procedures and entails unpredictable side effects resulting from Ab-induced crosslinking of DC surface molecules. In this study, we examined whether IgE, a high-affinity, non–cross-linking natural ligand of FcεRI, could be used to target Ags to DCs and to induce Ag-specific T cell tolerance. We found that Ag-conjugated human IgE Fc domain (Fcε) effectively delivered Ags to DCs and enhanced Ag presentation by 1000- to 2500-fold in human FcεRIα-transgenic mice. Importantly, this presentation resulted in a systemic deletion of Ag-specific T cells and prevented these mice from developing delayed-type hypersensitivity, which is critically dependent on Ag-specific T cell immunity. Thus, targeting FcεRI on DCs via Ag-Fcε fusion protein may serve an alternative method to induce Ag-specific T cell tolerance in humans. PMID:24610015

[Increase in orders for specific IgE tests and more positive results in children in 1985-2003].

PubMed

Baatenburg de Jong, A; Dikkeschei, L D; Brand, P L P

2008-08-09

To describe changes over time in the number of allergy tests for specific IgE ordered and outcomes in children, to help address the question whether the increase in allergies is due to an actual increase in sensitisation or an increase in diagnostic awareness of allergies among physicians. Retrospective and descriptive. We reviewed the results of all specific IgE tests performed in our hospital's laboratory for children 0-18 years of age in the period 1985-2003. This included tests ordered by both general practitioners and hospital-based specialists. We analysed trends over time in the number of tests ordered (as an indicator ofdiagnostic awareness) and test results (as an indicator ofsensitisation). Between 1989 and 1995, the annual number of tests ordered increased from 1 per 10,000 children to 95 per 10,000 children and remained stable thereafter. Before 1990, more than 90% of tests were ordered by hospital-based specialists; after 1990, approximately 70% of the tests were ordered by general practitioners (p < 0.001). The proportion of positive tests remained stable at approximately 27% until 1991, after which it increased to more than 45% (p < 0.001). The increase in the proportion of positive tests suggests an increase in atopic sensitization between 1985 and 2000 which has stabilized since.

House dust-mite allergen exposure is associated with serum specific IgE but not with respiratory outcomes.

PubMed

Bakolis, I; Heinrich, J; Zock, J P; Norbäck, D; Svanes, C; Chen, C M; Accordini, S; Verlato, G; Olivieri, M; Jarvis, D

2015-06-01

Exposure to house dust has been associated with asthma in adults, and this is commonly interpreted as a direct immunologic response to dust-mite allergens in those who are IgE sensitized to house dust-mite. Mattress house dust-mite concentrations were measured in a population-based sample of 2890 adults aged between 27 and 56 years living in 22 centers in 10 countries. Generalized linear mixed models were employed to explore the association of respiratory symptoms with house dust-mite concentrations, adjusting for individual and household confounders. There was no overall association of respiratory outcomes with measured house dust-mite concentrations, even in those who reported they had symptoms on exposure to dust and those who had physician-diagnosed asthma. However, there was a positive association of high serum specific IgE levels to HDM (>3.5 kUA /l) with mattress house dust-mite concentrations and a negative association of sensitization to cat with increasing house dust-mite concentrations. In conclusion, there was no evidence that respiratory symptoms in adults were associated with exposure to house dust-mite allergen in the mattress, but an association of house mite with strong sensitization was observed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

IgE antibody responses to platinum group metals: a large scale refinery survey.

PubMed Central

Murdoch, R D; Pepys, J; Hughes, E G

1986-01-01

All 306 South African platinum refinery workers (116 white, 190 coloured) accepted for employment on grounds of absence of evidence of atopy were investigated using the skin prick test and RAST to detect sensitivity to platinum, palladium, and rhodium salts. RAST studies were made for these, together with HSA and DNP-HSA RAST. Of the 306 workers, 38 had a positive skin prick test to the platinum halide salts; of these, one gave a positive reaction to the palladium salt and six to the rhodium salt. There were no isolated positives to the rhodium and palladium halide salts. Total IgE levels were raised in 24 of the 38 (63%) platinum salt prick test positive workers compared with only 43 of the 268 (16%) prick test negative group (p less than 0.001). Positive RASTs were obtained in 62% of those with positive skin tests to the platinum salts. Four of the six giving positive rhodium salt skin tests gave a positive RAST to rhodium salt. Of these, two gave positive RASTS to HSA and all four to DNP-HSA. The palladium salt RAST was negative in the single skin test reactor. In the platinum salt skin test positive group a raised HSA RAST was obtained in 10.5% compared with only 2.5% in the skin negative group. Twenty one per cent of the platinum salt skin positive group had a raised RAST score to DNP-HSA with only 3.5% (4/116) in the skin test negative group, of whom three also had a raised HSA RAST. The latter findings are suggestive of IgE antibody production to new antigenic determinants in HSA produced by conjugation with the platinum salts. PMID:2936374

OVA-bound nanoparticles induce OVA-specific IgG1, IgG2a, and IgG2b responses with low IgE synthesis.

PubMed

Yanase, Noriko; Toyota, Hiroko; Hata, Kikumi; Yagyu, Seina; Seki, Takahiro; Harada, Mitsunori; Kato, Yasuki; Mizuguchi, Junichiro

2014-10-14

There is an urgent requirement for a novel vaccine that can stimulate immune responses without unwanted toxicity, including IgE elevation. We examined whether antigen ovalbumin (OVA) conjugated to the surface of nanoparticles (NPs) (OVA-NPs) with average diameter of 110nm would serve as an immune adjuvant. When BALB/c mice were immunized with OVA-NPs, they developed sufficient levels of OVA-specific IgG1 antibody responses with low levels of IgE synthesis, representing helper T (Th)2-mediated humoral immunity. OVA-specific IgG2a and IgG2b responses (i.e., Th1-mediated immunity) were also induced by secondary immunization with OVA-NPs. As expected, immunization with OVA in alum (OVA-alum) stimulated humoral immune responses, including IgG1 and IgE antibodies, with only low levels of IgG2a/IgG2b antibodies. CD4-positive T cells from mice primed with OVA-NPs produced substantial levels of IL-21 and IL-4, comparable to those from OVA-alum group. The irradiated mice receiving OVA-NPs-primed B cells together with OVA-alum-primed T cells exhibited enhanced anti-OVA IgG2b responses relative to OVA-alum-primed B cells and T cells following stimulation with OVA-NPs. Moreover, when OVA-NPs-primed, but not OVA-alum-primed, B cells were cultured in the presence of anti-CD40 monoclonal antibody, IL-4, and IL-21, or LPS plus TGF-β in vitro, OVA-specific IgG1 or IgG2b antibody responses were elicited, suggesting that immunization with OVA-NPs modulates B cells to generate IgG1 and IgG2b responses. Thus, OVA-NPs might exert their adjuvant action on B cells, and they represent a promising potential vaccine for generating both IgG1 and IgG2a/IgG2b antibody responses with low IgE synthesis. Copyright © 2014 Elsevier Ltd. All rights reserved.

A retrospective analysis of cross-reacting cetuximab IgE antibody and its association with severe infusion reactions.

PubMed

Maier, Sabine; Chung, Christine H; Morse, Michael; Platts-Mills, Thomas; Townes, Leigh; Mukhopadhyay, Pralay; Bhagavatheeswaran, Prabhu; Racenberg, Jan; Trifan, Ovidiu C

2015-01-01

Severe infusion reactions (SIRs) at rates of 5% or less are known side effects of biological agents, including mAbs such as cetuximab. There are currently no prospectively validated risk factors to aid physicians in identifying patients who may be at risk of experiencing an SIR following administration of any of these drugs. A retrospective analysis of 545 banked serum or plasma samples from cancer patients participating in clinical trials of cetuximab was designed to evaluate whether the presence of pretreatment IgE antibodies against cetuximab, as determined by a commercially available assay system, is associated with SIRs during the initial cetuximab infusion. Patients with a positive test indicating the presence of pretreatment antibodies had a higher risk of experiencing an SIR; however, at the prespecified cutoff utilized in this analysis, the test has a relatively low-positive predictive value (0.577 [0.369-0.766]) and a negative predictive value of 0.961 (0.912-0.987) in an unselected patient population. Data collected in this large retrospective validation study support prior observations of an association between the presence of pretreatment IgE antibodies cross-reactive with cetuximab and SIRs. Further analysis of the test's ability to predict patients at risk of an SIR would be required before this assay could be used reliably in this patient population. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Determination of IgE antibodies to the benzylpenicilloyl determinant: a comparison of the sensitivity and specificity of three radio allergo sorbent test methods.

PubMed

Garcia, J J; Blanca, M; Moreno, F; Vega, J M; Mayorga, C; Fernandez, J; Juarez, C; Romano, A; de Ramon, E

1997-01-01

The quantitation of in vitro IgE antibodies to the benzylpenicilloyl determinant (BPO) is a useful tool for evaluating suspected penicillin allergic subjects. Although many different methods have been employed, few studies have compared their diagnostic specificity and sensitivity. In this study, the sensitivity and specificity of three different radio allergo sorbent test (RAST) methods for quantitating specific IgE antibodies to the BPO determinant were compared. Thirty positive control sera (serum samples from penicillin allergic subjects with a positive clinical history and a positive penicillin skin test) and 30 negative control sera (sera from subjects with no history of penicillin allergy and negative skin tests) were tested for BPO-specific IgE antibodies by RAST using three different conjugates coupled to the solid phase: benzylpenicillin conjugated to polylysine (BPO-PLL), benzylpenicillin conjugated to human serum albumin (BPO-HSA), and benzylpenicillin conjugated to an aminospacer (BPO-SP). Receiver operator control curves (ROC analysis) were carried out by determining different cut-off points between positive and negative values. Contingence tables were constructed and sensitivity, specificity, negative predictive values (PV-), and positive predictive values (PV+) were calculated. Pearson correlation coefficients (r) and intraclass correlation coefficients (ICC) were determined and the differences between methods were compared by chi 2 analysis. Analysis of the areas defined by the ROC curves showed statistical differences among the three methods. When cut-off points for optimal sensitivity and specificity were chosen, the BPO-HSA assay was less sensitive and less specific and had a lower PV- and PV+ than the BPO-PLL and BPO-SP assays. Assessment of r and ICC indicated that the correlation was very high, but the concordance between the PLL and SP methods was higher than between the PLL and HSA or SP and HSA methods. We conclude that for quantitating IgE

Identification and expression of an allergen Asp f 13 from Aspergillus fumigatus and epitope mapping using human IgE antibodies and rabbit polyclonal antibodies.

PubMed Central

Chow, L P; Liu, S L; Yu, C J; Liao, H K; Tsai, J J; Tang, T K

2000-01-01

The Aspergillus genus of fungi is known to be one of the most prevalent aeroallergens. On two-dimensional immunoblotting using patients' sera containing IgE specific for Asp f 13, an allergen with a molecular mass of 33 kDa and a pI of 6.2 was identified. This allergen was also present in A. fumigatus culture filtrates. Furthermore, the sequence of the Asp f 13 cDNA was identical to that for alkaline protease isolated from A. fumigatus and showed 42-49% identity of amino acids with two proteases from P. cyclopium and T. album and with the Pen c 1 allergen from P. citrinum. Asp f 13 coding sequences were expressed in Escherichia coli as a [His](6)-tagged fusion protein which was purified by Ni(2+)-chelate affinity chromatography. Recombinant Asp f 13 was recognized by rabbit polyclonal antibodies against Asp f 13 and by IgE antibodies from subject allergic to A. fumigatus. To identify and characterize the linear epitopes of this allergen, a combination of chemical and enzymatic cleavage and immunoblotting techniques, with subsequent N-terminal sequencing and mass spectrometry, were performed. At least 13 different linear epitopes reacting with the rabbit anti-Asp f 13 antiserum were identified, located throughout the entire molecule. In contrast, IgE from A. fumigatus-sensitive patients bound to three immunodominant epitopes at the C-terminal of the protein. PMID:10677362

IgE antibodies and urinary trimethylarsine oxide accounted for 1-7% population attributable risks for eczema in adults: USA NHANES 2005-2006.

PubMed

Shiue, Ivy

2015-12-01

Population attributable risks from serum IgE and dust miteallergen concentrations and environmental chemicals for eczema are unclear. Therefore, it was aimed to examine serum IgE and allergen concentrations and environmental chemicals for eczema in adults and to calculate population attributable risks in a national and population-based setting. Data retrieved from the National Health and Nutrition Examination Survey, 2005-2006, was analyzed. Information on demographics and self-reported ever eczema was obtained by household interview. Bloods and urines (sub-sample) were also collected during the interview. Adults aged 20-85 were included. Statistical analyses were using chi-square test, t test, survey-weighted logistic regression modeling, and population attributable risk (PAR) estimation. Of all the included American adults (n = 4979), 310 (6.2%) reported ever eczema. Moreover, more eczema cases were observed in female adults but fewer cases in people born in Mexico. There were no significant associations observed between commonly known biomarkers (including vitamin D) and eczema or between dust mite allergens and eczema. Serum D. Farinae (PAR 1.0%), D. Pteronyssinus (PAR 1.1%), cat (PAR 1.8%), dog (PAR 1.6%), and muse (PAR 3.2%) IgE antibodies were associated with eczema. Adults with ever eczema were found to have higher levels of urinary trimethylarsine oxide concentrations (PAR 7.0%) but not other speciated arsenic concentrations. There were no clear associations between other environmental chemicals including heavy metals, phthalates, phenols, parabens, pesticides, nitrate, perchlorate, polycyclic hydrocarbons and eczema as well. Elimination of environmental risks might help delay or stop eczema up to 7% in the adult population.

Development of sandwich ELISA for testing bovine β-lactoglobulin allergenic residues by specific polyclonal antibody against human IgE binding epitopes.

PubMed

He, Shengfa; Li, Xin; Gao, Jinyan; Tong, Ping; Chen, Hongbing

2017-07-15

Bovine β-lactoglobulin (BLG) is the main allergen in cows' milk, and the most commonly used method for detecting BLG is enzyme-linked immunosorbent assay (ELISA). However, antibodies used in commercial ELISA kits do not recognize specifically BLG IgE epitopes. Here, an antibody specific to IgE linear epitopes for BLG was used to develop a sandwich ELISA using a rabbit anti-BLG polyclonal antibody. The linear range for BLG detection was 31.25-8000ng/mL and limit of detection was 1.96ng/mL. BLG content in dairy samples was determined, and there was a good agreement between this immunoassay and reversed-phase high-performance liquid chromatography with high recovery. Additionally, BLG content in food samples had an average recovery of 104.25%. Allergenic residues were also detected in hydrolyzed infant formulas. The method developed could be a practical approach to determine BLG and its allergenic residues in food with a high degree of sensitivity, reliability and recovery. Copyright © 2017 Elsevier Ltd. All rights reserved.

Delayed anaphylaxis involving IgE to galactose-alpha-1,3-galactose

PubMed Central

Platts-Mills, Thomas A E; Schuyler, Alexander J; Hoyt, Alice E W; Commins, Scott P

2015-01-01

Hypersensitivity in the allergic setting refers to immune reactions, stimulated by soluble antigens that can be rapidly progressing and, in the case of anaphylaxis, are occasionally fatal. As the number of known exposures associated with anaphylaxis is limited, identification of novel causative agents is important in facilitating both education and other allergen-specific approaches that are crucial to long-term risk management. Within the last 10 years several seemingly separate observations were recognized to be related, all of which resulted from the development of antibodies to a carbohydrate moiety on proteins where exposure differed from airborne allergens but which were nevertheless capable of producing anaphylactic and hypersensitivity reactions. Our recent work has identified these responses as being due to a novel IgE antibody directed against a mammalian oligosaccharide epitope, galactose-alpha-1,3-galactose (alpha-gal). This review will present the history and biology of alpha-gal and discuss our current approach to management of the mammalian meat allergy and delayed anaphylaxis. PMID:26130470

Prediction of tolerance in children with IgE mediated cow's milk allergy by microarray profiling and chemometric approach.

PubMed

Wulfert, F; Sanyasi, G; Tongen, L; Watanabe, L A; Wang, X; Renault, N K; Falcone, F H; Jacob, C M A; Alcocer, M J C

2012-08-31

The sera of a retrospective cohort (n=41) composed of children with well characterized cow's milk allergy collected from multiple visits were analyzed using a protein microarray system measuring four classes of immunoglobulins. The frequency of the visits, age and gender distribution reflected real situation faced by the clinicians at a pediatric reference center for food allergy in São Paulo, Brazil. The profiling array results have shown that total IgG and IgA share similar specificity whilst IgM and in particular IgE are distantly related. The correlation of specificity of IgE and IgA is variable amongst the patients and this relationship cannot be used to predict atopy or the onset of tolerance to milk. The array profiling technique has corroborated the clinical selection criteria for this cohort albeit it clearly suggested that 4 out of the 41 patients might have allergies other than milk origin. There was also a good correlation between the array data and ImmunoCAP results, casein in particular. By using qualitative and quantitative multivariate analysis routines it was possible to produce validated statistical models to predict with reasonable accuracy the onset of tolerance to milk proteins. If expanded to larger study groups, the array profiling in combination with the multivariate techniques show potential to improve the prognostic of milk allergic patients. Copyright © 2012 Elsevier B.V. All rights reserved.

Increased human IgE induced by killing Schistosoma mansoni in vivo is associated with pretreatment Th2 cytokine responsiveness to worm antigens.

PubMed

Walter, Klaudia; Fulford, Anthony J C; McBeath, Rowena; Joseph, Sarah; Jones, Frances M; Kariuki, H Curtis; Mwatha, Joseph K; Kimani, Gachuhi; Kabatereine, Narcis B; Vennervald, Birgitte J; Ouma, John H; Dunne, David W

2006-10-15

In schistosomiasis endemic areas, children are very susceptible to postchemotherapy reinfection, whereas adults are relatively resistant. Different studies have reported that schistosome-specific IL-4 and IL-5 responses, or posttreatment worm-IgE levels, correlate with subsequent low reinfection. Chemotherapy kills i.v. worms providing an in vivo Ag challenge. We measured anti-worm (soluble worm Ag (SWA) and recombinant tegumental Ag (rSm22.6)) and anti-egg (soluble egg Ag) Ab levels in 177 Ugandans (aged 7-50) in a high Schistosoma mansoni transmission area, both before and 7 wk posttreatment, and analyzed these data in relation to whole blood in vitro cytokine responses at the same time points. Soluble egg Ag-Ig levels were unaffected by treatment but worm-IgG1 and -IgG4 increased, whereas worm-IgE increased in many but not all individuals. An increase in worm-IgE was mainly seen in >15-year-olds and, unlike in children, was inversely correlated to pretreatment infection intensities, suggesting this response was associated both with resistance to pretreatment infection, as well as posttreatment reinfection. The increases in SWA-IgE and rSm22.6-IgE positively correlated with pretreatment Th2 cytokines, but not IFN-gamma, induced by SWA. These relationships remained significant after allowing for the confounding effects of pretreatment infection intensity, age, and pretreatment IgE levels, indicating a link between SWA-specific Th2 cytokine responsiveness and subsequent increases in worm-IgE. An exceptionally strong relationship between IL-5 and posttreatment worm-IgE levels in < 15-year-olds suggested that the failure of younger children to respond to in vivo Ag stimulation with increased levels of IgE, is related to their lack of pretreatment SWA Th2 cytokine responsiveness.

Practical interest of both skin prick test and specific IgE in the evaluation of tolerance acquisition in IgE mediated cow's milk allergy (CMA). A clinical retrospective study in a cohort of 184 children.

PubMed

Payot, F; Berthiller, J; Kassai, B; Brunet, A-S; Villard-Truc, F; Lachaux, A

2014-01-01

Cow's milk protein allergy (CMPA) represents one of the leading causes of food allergy in infants and young children. The immune reaction may be IgE mediated, non-IgE mediated, or mixed. IgE-mediated cow's milk protein allergy is revealed by immediate and acute symptoms which can be severe. The aim of this study is to report a one centre experience in the real life of testing children with IgE-mediated CMPA and try to identify predictive factor for follow-up challenges. Retrospective and monocentric study between September 1997 and February 2008. 178 infants diagnosed with IgE-mediated CMPA during breastfeeding weaning were included. Initial factors such as age, sex, skin prick tests (SPTs), specific IgE (sIgE), atopic dermatitis and types of reaction were noted. Between 12 and 24 months all infants have undergone at least one evaluation including SPT. At the food challenge, 138 (75.8%) infants were found tolerant. Results of the skin prick test (SPT) were statistically different according to the food challenge result (2.2mm vs. 5.1mm, p<0.0001). It was the same result for sIgE for CM 2.0ku/l vs. 11.5ku/l - p<0.0001 and for casein 1.0ku/l vs. 16.0ku/l - p=0.0014. This study confirms the practical interest of both SPT and sIgE in the evaluation of tolerance induction in IgE-mediated CMPA, but with no corresponding results. Sensitivity, specificity and probability curves of success for cow's milk challenge can be determined and have clinical utility. Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.

Discordance between Aeroallergen Specific Serum IgE and Skin Testing in Children < 4 years of age

PubMed Central

de Vos, Gabriele; Nazari, Ramin; Ferastraoaru, Denisa; Parikh, Purvi; Geliebter, Rebecca; Pichardo, Yikania; Wiznia, Andrew; Rosenstreich, David

2015-01-01

Background Atopic sensitization to aeroallergens in early life has been shown to be a strong risk factor for developing persisting asthma in young children with recurrent wheeze. Objective The aim of this study was to assess the yield of skin prick test (SPT) compared to allergen specific serum IgE testing (sIgE) at identifying aeroallergen sensitization in atopic children < 4 years of age. Methods Concordance between SPT (Greer Laboratories, ComforTen™) and allergen specific sIgE (Immulite 2000™) for 7 common aeroallergens was analyzed in forty atopic inner-city children, 18–48 months of age (mean 36 +/− 9 months) with recurrent wheezing, family history of asthma and/or eczema. Results In 80% of children one or more allergen sensitizations would have been missed if only SPT had been performed, and in 38% of children one or more sensitizations would have been missed if only serum IgE testing had been performed. Agreement and between SPT and sIgE test was fair for most allergens (kappa between −0.04 and 0.50), as was correlation between sIgE levels and SPT grade (rho between 0.21 and 0.55). Children with high total sIgE (≥300 kU/l) were more likely to have sIgE positive tests with negative corresponding skin test (p=0.025). Conclusions Our study showed significant discordance between allergen specific SPT and sIgE testing results for common aeroallergens, suggesting that both SPT and sIgE testing should be done when diagnosing allergic sensitization in young children at high risk of asthma. PMID:23706713

Epicutaneous immunization with ovalbumin and CpG induces TH1/TH17 cytokines, which regulate IgE and IgG2a production

PubMed Central

Majewska-Szczepanik, Monika; Askenase, Philip W.; Lobo, Francis M.; Marcińska, Katarzyna; Wen, Li; Szczepanik, Marian

2017-01-01

Background Subcutaneous allergen-specific immunotherapy is a standard route for the immunotherapy of allergic diseases. It modulates the course of allergy and can generate long-term remission. However, subcutaneous allergen-specific immunotherapy can also induce anaphylaxis in some patients, and therefore additional routes of administration should be investigated to improve the safety and tolerability of immunotherapy. Objective We sought to determine whether epicutaneous treatment with antigen in the presence of a Toll-like receptor 9 agonist can suppress TH2-mediated responses in an antigen-specific manner. Methods Epicutaneous immunization was performed by applying a skin patch soaked with ovalbumin (OVA) plus CpG, and its suppressor activity was determined by using the mouse model of atopic dermatitis. Finally, adoptive cell transfers were implemented to characterize the regulatory cells that are induced by epicutaneous immunization. Results Epicutaneous immunization with OVA and CpG reduces the production of OVA-specific IgE and increases the synthesis of OVA-specific IgG2a antibodies in an antigen-specific manner. Moreover, eosinophil peroxidase activity in the skin and production of IL-4, IL-5, IL-10, and IL-13 are suppressed. The observed reduction of IgE synthesis is transferable with T-cell receptor (TCR) αβ+CD4+CD25− cells, whereas IgG2a production is dependent on both TCRαβ+ and TCRγδ+ T cells. Further experiments show that the described phenomenon is myeloid differentiation primary response 88, IFN-γ, and IL-17A dependent. Finally, the results suggest that epicutaneous immunization with OVA and CpG decreases the synthesis of OVA-specific IgE and skin eosinophil peroxidase activity in mice with ongoing skin allergy. Conclusion Epicutaneous application of protein antigen in the presence of adjuvant could be an attractive needle-free and self-administered immunotherapy for allergic diseases. PMID:26810716

Deficiency of a Disintegrin and Metalloproteinase 10 (ADAM10) on dendritic cells prevents the development of type 2 immunity and IgE production

USDA-ARS?s Scientific Manuscript database

Mice in which dendritic cells (DCs)lack ADAM10 (ADAM10DC-/-) were found to have a dramatic decrease in TH2 immunity and IgE production, as measured by both lung inflammation to house dust mite (HDM) and active systemic anaphylaxis models (ASA). With HDM, the ADAM10DC-/- had significantly less airway...

IgG and IgG4 to 91 allergenic molecules in early childhood by route of exposure and current and future IgE sensitization: Results from the Multicentre Allergy Study birth cohort.

PubMed

Schwarz, Alina; Panetta, Valentina; Cappella, Antonio; Hofmaier, Stephanie; Hatzler, Laura; Rohrbach, Alexander; Tsilochristou, Olympia; Bauer, Carl-Peter; Hoffmann, Ute; Forster, Johannes; Zepp, Fred; Schuster, Antje; D'Amelio, Raffaele; Wahn, Ulrich; Keil, Thomas; Lau, Susanne; Matricardi, Paolo Maria

2016-11-01

Studies of a limited number of allergens suggested that nonsensitized children produce IgG responses mainly to foodborne allergens, whereas IgE-sensitized children also produce strong IgG responses to the respective airborne molecules. We sought to systematically test the hypothesis that both the route of exposure and IgE sensitization affect IgG responses to a broad array of allergenic molecules in early childhood. We examined sera of 148 children participating in the Multicentre Allergy Study, a birth cohort born in 1990. IgG to 91 molecules of 42 sources were tested with the ImmunoCAP Solid-Phase Allergen Chip (ISAC; TFS, Uppsala, Sweden). IgE sensitization at age 2 and 7 years was defined by IgE levels of 0.35 kU A /L or greater to 1 or more of 8 or 9 extracts from common allergenic sources, respectively. The prevalence and geometric mean levels of IgG to allergenic molecules in nonsensitized children were lower at age 2 years than in IgE-sensitized children, and they were extremely heterogeneous: highest for animal food (87% ± 13%; 61 ISAC Standardized Units [ISU], [95% CI, 52.5-71.5 ISU]), intermediate for vegetable food (48% ± 27%; 13 ISU [95% CI, 11.2-16.1 ISU]), and lowest for airborne allergens (24% ± 20%; 3 ISU [95% CI, 2.4-3.4 ISU]; P for trend < .001 [for percentages], P for trend < .001 [for levels]). IgG 4 antibodies were infrequent (<5%) and contributed poorly (<3%) to overall IgG antibody levels. IgG responses at age 2 years were slightly more frequent and stronger among children with than in those without IgE sensitization at age 7 years. The children's repertoire of IgG antibodies at 2 years of age to a broad array of animal foodborne, vegetable foodborne, and airborne allergenic molecules is profoundly dependent on the route of allergen exposure and the child's IgE sensitization status and only marginally involves the IgG 4 isotype. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc

Skin prick testing predicts peanut challenge outcome in previously allergic or sensitized children with low serum peanut-specific IgE antibody concentration.

PubMed

Nolan, Richard C; Richmond, Peter; Prescott, Susan L; Mallon, Dominic F; Gong, Grace; Franzmann, Annkathrin M; Naidoo, Rama; Loh, Richard K S

2007-05-01

Peanut allergy is transient in some children but it is not clear whether quantitating peanut-specific IgE by Skin Prick Test (SPT) adds additional information to fluorescent-enzyme immunoassay (FEIA) in discriminating between allergic and tolerant children. To investigate whether SPT with a commercial extract or fresh foods adds additional predictive information for peanut challenge in children with a low FEIA (<10 k UA/L) who were previously sensitized, or allergic to peanuts. Children from a hospital-based allergy service who were previously sensitized or allergic to peanuts were invited to undergo a peanut challenge unless they had a serum peanut-specific IgE>10 k UA/L, a previous severe reaction, or a recent reaction to peanuts (within two years). SPT with a commercial extract, raw and roasted saline soaked peanuts was performed immediately prior to open challenge in hospital with increasing quantity of peanuts until total of 26.7 g of peanut was consumed. A positive challenge consisted of an objective IgE mediated reaction occurring during the observation period. 54 children (median age of 6.3 years) were admitted for a challenge. Nineteen challenges were positive, 27 negative, five were indeterminate and three did not proceed after SPT. Commercial and fresh food extracts provided similar diagnostic information. A wheal diameter of >or=7 mm of the commercial extract predicted an allergic outcome with specificity 97%, positive predictive value 93% and sensitivity 83%. There was a tendency for an increase in SPT wheal since initial diagnosis in children who remained allergic to peanuts while it decreased in those with a negative challenge. The outcome of a peanut challenge in peanut sensitized or previously allergic children with a low FEIA can be predicted by SPT. In this cohort, not challenging children with a SPT wheal of >or=7 mm would have avoided 15 of 18 positive challenges and denied a challenge to one out of 27 tolerant children.

IgE recognition patterns in peanut allergy are age dependent: perspectives of the EuroPrevall study.

PubMed

Ballmer-Weber, B K; Lidholm, J; Fernández-Rivas, M; Seneviratne, S; Hanschmann, K M; Vogel, L; Bures, P; Fritsche, P; Summers, C; Knulst, A C; Le, T M; Reig, I; Papadopoulos, N G; Sinaniotis, A; Belohlavkova, S; Popov, T; Kralimarkova, T; de Blay, F; Purohit, A; Clausen, M; Jedrzejczak-Czechowcz, M; Kowalski, M L; Asero, R; Dubakiene, R; Barreales, L; Clare Mills, E N; van Ree, R; Vieths, S

2015-04-01

We tested the hypothesis that specific molecular sensitization patterns correlate with the clinical data/manifestation in a European peanut-allergic population characterized under a common protocol. Sixty-eight peanut-allergic subjects and 82 tolerant controls from 11 European countries were included. Allergy to peanut and lowest symptom-eliciting dose was established by double-blind placebo-controlled food challenge in all but anaphylactic subjects. Information of early or late (before or after 14 years of age) onset of peanut allergy was obtained from standardized questionnaires. IgE to peanut allergens rAra h 1-3, 6, 8-9, profilin and CCD was determined using ImmunoCAP. Seventy-eight percent of peanut allergics were sensitized to peanut extract and 90% to at least one peanut component. rAra h 2 was the sole major allergen for the peanut-allergic population. Geographical differences were observed for rAra h 8 and rAra h 9, which were major allergens for central/western and southern Europeans, respectively. Sensitization to rAra h 1 and 2 was exclusively observed in early-onset peanut allergy. Peanut-tolerant subjects were frequently sensitized to rAra h 8 or 9 but not to storage proteins. Sensitization to Ara h 2 ≥ 1.0 kUA /l conferred a 97% probability for a systemic reaction (P = 0.0002). Logistic regression revealed a significant influence of peanut extract sensitization and region on the occurrence of systemic reactions (P = 0.0185 and P = 0.0436, respectively). Sensitization to Ara h 1, 2 and 3 is usually acquired in childhood. IgE to Ara h 2 ≥ 1.0 kUA /l is significantly associated with the development of systemic reactions to peanut. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Possible orientational constraints determine secretory signals induced by aggregation of IgE receptors on mast cells.

PubMed Central

Ortega, E; Schweitzer-Stenner, R; Pecht, I

1988-01-01

Three biologically active monoclonal antibodies (mAbs) specific for the monovalent, high-affinity membrane receptor for IgE (Fc epsilon R) were employed in analysing the secretory response of mast cells of the RBL-2H3 line to crosslinking of their Fc epsilon R. All three mAbs (designated F4, H10 and J17) compete with each other and with IgE for binding to the Fc epsilon R. Their stoichiometry of binding is 1 Fab:1 Fc epsilon R, hence, the intact mAbs can aggregate the Fc epsilon Rs to dimers only. Since all three mAbs induce secretion, we conclude that Fc epsilon R dimers constitute a sufficient 'signal element' for secretion of mediators for RBL-2H3 cells. The secretory dose-response of the cells to these three mAbs are, however, markedly different: F4 caused rather high secretion, reaching almost 80% of the cells' content, while J17 and H10 induced release of only 30-40% mediators content. Both the intrinsic affinities and equilibrium constants for the receptor dimerization were derived from analysis of binding data of the Fab fragments and intact mAbs. These parameters were used to compute the extent of Fc epsilon R dimerization caused by each of the antibodies. However, the different secretory responses to the three mAbs could not be rationalized simply in terms of the extent of Fc epsilon R dimerization which they produce. This suggests that it is not only the number of crosslinked Fc epsilon Rs which determines the magnitude of secretion-causing signal, but rather other constraints imposed by each individual mAb are also important.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2977332

Structures of Two Major Allergens, Bla g 4 and Per a 4, From Cockroaches and Their IgE Binding Epitopes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan, Y.; Chan, S; Ong, T

2009-01-01

Inhalant allergens from cockroaches are an important cause of asthma to millions of individuals worldwide. Here we report for the first time the structures of two major cockroach allergens, Bla g 4 and Per a 4, that adopt a typical lipocalin fold but with distinct structural features as compared with other known lipocalin allergens. Both Bla g 4 and Per a 4 contain two long-range disulfide bonds linking the N and C termini to a beta-barrel. The C-terminal helix of Bla g 4 is bent and greatly extended toward the N terminus. Bla g 4 is found to be amore » monomer, whereas Per a 4 exists as a dimer in solution with a novel dimeric interface involving residues from loops at the top and bottom of the beta-barrel. Putative ligand binding sites of both allergens are determined by docking of the juvenile hormone III inside the beta-barrel and found to interact with the ligand using non-conserved residues. Bla g 4 and Per a 4 are found to be cross-reactive in sera IgE binding, at least in the Singaporean Chinese population tested. A major IgE binding epitope unique to Per a 4 is found on the loops at the bottom of the beta-barrel that may aid the development of hypoallergens for immunotherapy.« less

Prenatal environmental factors influencing IgE levels, atopy and early asthma.

PubMed

Peters, Junenette L; Boynton-Jarrett, Renée; Sandel, Megan

2013-04-01

There is increasing evidence that the prenatal window represents a critical period in which the developing immune system may be primed toward an allergic phenotype. Studies have investigated the role of a number of maternal environmental exposures on subsequent allergic disorders in the offspring. We summarize findings from recent studies on prenatal environmental factors influencing IgE levels, atopy, and early asthma. A building literature supports the influence of maternal exposure to environmental pollutants, such as allergens, traffic-related air pollution, tobacco smoke, and organochlorine compounds and social factors on allergic outcomes. More novel associations have been investigated, such as the effect of prenatal exposures to phthalates, bisphenol A, and magnetic fields. There is also rising interest in epigenetics as a pathway of action by which maternal exposure affect immune health. Emerging research highlights the challenges of investigating in-utero exposures and of relating exposures to such a heterogeneous and complex outcome as allergic disease. Further research is needed on the mechanisms by which prenatal exposure influences allergic response in childhood and how postnatal, familial and social factors, and sex can modify disease outcomes. Epigenetics is a promising new frontier, and likely one of several explanatory factors.

Molecular basis of pollen-related food allergy: identification of a second cross-reactive IgE epitope on Pru av 1, the major cherry (Prunus avium) allergen.

PubMed

Wiche, Regina; Gubesch, Michaela; König, Herbert; Fötisch, Kay; Hoffmann, Andreas; Wangorsch, Andrea; Scheurer, Stephan; Vieths, Stefan

2005-01-01

Birch (Betula verrucosa) pollen-associated food allergy is a well-characterized syndrome, which is due to the cross-reactivity of IgE antibodies to homologous allergens in various foods. One crossreacting area on the major birch pollen allergen Bet v 1 and its homologue in cherry (Prunus avium) Pru av 1 has already been identified. This is the so-called 'P-loop' region, which encompasses amino acid residues around position 45 and is found on the two virtually identical tertiary protein structures. We tried to determine an additional IgE cross-reacting patch on Pru av 1 and Bet v 1. The putative IgE-binding region on Pru av 1 was localized with a mAb (monoclonal antibody) that was generated against Bet v 1, and cross-reacts with several Bet v 1 homologues in food and inhibits the binding of patients' IgE to Pru av 1. mAb reactivity pattern was analysed and amino acid positions 28 and 108 of Pru av 1 were selected and mutated by site-directed mutagenesis. The Pru av 1 mutants were produced as recombinant proteins and characterized for their folding, mAb- and IgE-binding capacity and allergenic potency with a cellular assay using the humanized rat basophilic leukaemia cell line RBL-25/30. Amino acid position 28 is involved in a second major IgE-binding region on Pru av 1 and probably on Bet v 1. The identification of this second major IgE-binding region is an essential prerequisite to understand the phenomenon of cross-reactivity and its clinical consequences, and to produce hypoallergenic proteins for an improved immunotherapy of type I allergy.

Defects along the T(H)17 differentiation pathway underlie genetically distinct forms of the hyper IgE syndrome.

PubMed

Al Khatib, Shadi; Keles, Sevgi; Garcia-Lloret, Maria; Karakoc-Aydiner, Elif; Reisli, Ismail; Artac, Hasibe; Camcioglu, Yildiz; Cokugras, Haluk; Somer, Ayper; Kutukculer, Necil; Yilmaz, Mustafa; Ikinciogullari, Aydan; Yegin, Olcay; Yüksek, Mutlu; Genel, Ferah; Kucukosmanoglu, Ercan; Baki, Ali; Bahceciler, Nerin N; Rambhatla, Anupama; Nickerson, Derek W; McGhee, Sean; Barlan, Isil B; Chatila, Talal

2009-08-01

The hyper IgE syndrome (HIES) is characterized by abscesses, eczema, recurrent infections, skeletal and connective tissue abnormalities, elevated serum IgE, and diminished inflammatory responses. It exists as autosomal-dominant and autosomal-recessive forms that manifest common and distinguishing clinical features. A majority of those with autosomal-dominant HIES have heterozygous mutations in signal transducer and activator of transcription (STAT)-3 and impaired T(H)17 differentiation. To elucidate mechanisms underlying different forms of HIES. A cohort of 25 Turkish children diagnosed with HIES were examined for STAT3 mutations by DNA sequencing. Activation of STAT3 by IL-6 and IL-21 and STAT1 by IFN-alpha was assessed by intracellular staining with anti-phospho (p)STAT3 and -pSTAT1 antibodies. T(H)17 and T(H)1 cell differentiation was assessed by measuring the production of IL-17 and IFN-gamma, respectively. Six subjects had STAT3 mutations affecting the DNA binding, Src homology 2, and transactivation domains, including 3 novel ones. Mutation-positive but not mutation-negative subjects with HIES exhibited reduced phosphorylation of STAT3 in response to cytokine stimulation, whereas pSTAT1 activation was unaffected. Both patient groups exhibited impaired T(H)17 responses, but whereas STAT3 mutations abrogated early steps in T(H)17 differentiation, the defects in patients with HIES with normal STAT3 affected more distal steps. In this cohort of Turkish children with HIES, a majority had normal STAT3, implicating other targets in disease pathogenesis. Impaired T(H)17 responses were evident irrespective of the STAT3 mutation status, indicating that different genetic forms of HIES share a common functional outcome.

Comparison of serum specific IgE with skin prick test in the diagnosis of allergy in Malaysia.

PubMed

Asha'ari, Z A; Suhaimi, Y; Yusof, R A; Rushdan, I; Maraina, C H C

2011-08-01

We compared a newer serum specific IgE (SSIgE) test with skin prick testing (SPT) in the diagnosis of allergy in Malaysia. Ninety newly diagnosed allergic patients were enrolled for both tests. Using SPT as a clinical gold standard, the sensitivity, specificity, positive, and negative predictive values (PPV, NPV) were calculated for SSIgE for each of the common allergens tested. The highest positive results for both SPT and SSIgE were for house dust mite and cat. Compared to SPT, SSIgE showed better sensitivity but poorer specificity, low PPV and good NPV in all the allergens tested. Significant positive correlation was seen between the diameter of wheal and flare of SPT and the SSIgE results.

Molecular basis of pollen-related food allergy: identification of a second cross-reactive IgE epitope on Pru av 1, the major cherry (Prunus avium) allergen

PubMed Central

2004-01-01

Birch (Betula verrucosa) pollen-associated food allergy is a well-characterized syndrome, which is due to the cross-reactivity of IgE antibodies to homologous allergens in various foods. One crossreacting area on the major birch pollen allergen Bet v 1 and its homologue in cherry (Prunus avium) Pru av 1 has already been identified. This is the so-called ‘P-loop’ region, which encompasses amino acid residues around position 45 and is found on the two virtually identical tertiary protein structures. We tried to determine an additional IgE cross-reacting patch on Pru av 1 and Bet v 1. The putative IgE-binding region on Pru av 1 was localized with a mAb (monoclonal antibody) that was generated against Bet v 1, and cross-reacts with several Bet v 1 homologues in food and inhibits the binding of patients' IgE to Pru av 1. mAb reactivity pattern was analysed and amino acid positions 28 and 108 of Pru av 1 were selected and mutated by site-directed mutagenesis. The Pru av 1 mutants were produced as recombinant proteins and characterized for their folding, mAb- and IgE-binding capacity and allergenic potency with a cellular assay using the humanized rat basophilic leukaemia cell line RBL-25/30. Amino acid position 28 is involved in a second major IgE-binding region on Pru av 1 and probably on Bet v 1. The identification of this second major IgE-binding region is an essential prerequisite to understand the phenomenon of cross-reactivity and its clinical consequences, and to produce hypoallergenic proteins for an improved immunotherapy of type I allergy. PMID:15330760

Prozone effect of serum IgE levels in a case of plasma cell leukemia

PubMed Central

2010-01-01

We describe a case of multiple myeloma (MM) and secondary plasma cell leukemia (PCL) secreting IgE-kappa immunoglobulin. To our knowledge, only 2 cases of IgE-producing secondary PCL have been reported in the medical literature. In our patient, the only tumor marker available for monitoring the therapeutic response to chemotherapy and allogeneic stem cell transplantation was the quantitative M component at serum protein electrophoresis (SPEP), because serum free light chains were in the normal range, Bence-Jones proteinuria was absent, and quantitative serum IgE levels provided inaccurate and erratic results, due to the prozone effect. This is a laboratory phenomenon that occurs when antigen excess interferes with antibody-based methods requiring immune complex formation for detection. It is important to recognize the presence of a prozone effect, because it can produce falsely normal results, and therefore it could lead clinicians to incorrect assessment of the response to therapy. PMID:20828419

Prozone effect of serum IgE levels in a case of plasma cell leukemia.

PubMed

Talamo, Giampaolo; Castellani, William; Dolloff, Nathan G

2010-09-10

We describe a case of multiple myeloma (MM) and secondary plasma cell leukemia (PCL) secreting IgE-kappa immunoglobulin. To our knowledge, only 2 cases of IgE-producing secondary PCL have been reported in the medical literature. In our patient, the only tumor marker available for monitoring the therapeutic response to chemotherapy and allogeneic stem cell transplantation was the quantitative M component at serum protein electrophoresis (SPEP), because serum free light chains were in the normal range, Bence-Jones proteinuria was absent, and quantitative serum IgE levels provided inaccurate and erratic results, due to the prozone effect. This is a laboratory phenomenon that occurs when antigen excess interferes with antibody-based methods requiring immune complex formation for detection. It is important to recognize the presence of a prozone effect, because it can produce falsely normal results, and therefore it could lead clinicians to incorrect assessment of the response to therapy.

Asp f6, an Aspergillus allergen specifically recognized by IgE from patients with allergic bronchopulmonary aspergillosis, is differentially expressed during germination.

PubMed

Schwienbacher, M; Israel, L; Heesemann, J; Ebel, F

2005-11-01

Aspergillus fumigatus is a pathogenic mould causing allergic and invasive respiratory diseases. Allergic bronchopulmonary Aspergillosis (ABPA) is a severe pulmonary complication resulting from hypersensitivity to A. fumigatus proteins. Aspergillus allergen Asp f6 is recognized by IgE from ABPA patients, but not from sensitized individuals, a fact that can be used to differentiate between these two groups of allergic patients. Proteins from hyphae, resting and germinating conidia of A. fumigatus were compared by SDS-PAGE. Protein identification was performed using MALDI-TOF mass spectrometry. Recombinant A. fumigatus allergens were used to isolate specific monoclonal antibodies (mab) from a hybridoma bank generated against Aspergillus proteins. A hyphae-specific 23 kDa A. fumigatus protein was identified as the allergen Asp f6/manganese-dependent superoxide dismutase (MnSOD). Differential expression of MnSOD was confirmed by immunoblot using a specific mab. In contrast, Asp f8 another intracellular, but not ABPA-specific allergen, was detected in hyphae and conidia. Aspergillus fumigatus is able to colonize its environment by the formation of hyphae. Hyphae are found in the lung of ABPA patients, but not in patients suffering from atopic asthma. Our finding that Asp f6 is specifically expressed in hyphae might explain why an IgE response to Asp f6 is specific for ABPA patients.

Minimizing fucosylation in insect cell-derived glycoproteins reduces binding to IgE antibodies from the sera of patients with allergy.

PubMed

Palmberger, Dieter; Ashjaei, Kazem; Strell, Stephanie; Hoffmann-Sommergruber, Karin; Grabherr, Reingard

2014-09-01

The baculovirus/insect cell system has proven to be a very powerful tool for the expression of several therapeutics. Nevertheless, these products sometimes suffer from reduced biological activity and unwanted side effects. Several studies have demonstrated that glycosylation can greatly influence the structure, function, half-life, antigenicity and immunogenicity of various glycoproteins. Yet, the glycosylation pattern of insect cell-derived products is not favorable for many applications. Especially, the presence of core α1,3-linked fucose bears the risk of causing immediate hypersensitivity reactions in patients with allergy. In this study, we evaluated the impact of fucose residues on the allergenic potential of an insect cell-expressed vaccine candidate. In order to block the GDP-L-fucose de novo synthesis pathway, we integrated the Pseudomonas aeruginosa GDP-6-deoxy-D-lyxo-4-hexulose reductase (RMD) gene into a baculovirus backbone. This virus was then used for the expression of soluble influenza A virus hemagglutinin (HA). Expression studies showed that the co-expression of RMD did not influence the overall level of recombinant protein secretion. We confirmed the result of our strategy by analyzing PNGase A-released N-glycans using MALDI-TOF-MS. In order to evaluate the biological impact of defucosylation of influenza HA we tested the binding activity of IgE derived from the sera of patients with allergy to the purified antigen. The non-fucosylated HA showed a 10-fold decrease in IgE binding levels as compared to wildtype variants. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Allergen-specific IgE measurement with the IMMULITE 2000 system: intermethod comparison of detection performance for allergen-specific IgE antibodies from Korean allergic patients.

PubMed

Lee, Yong Won; Sohn, Jung Ho; Lee, Jae-Hyun; Hong, Chein-Soo; Park, Jung-Won

2009-03-01

Intermethod comparison between IMMULITE 2000 chemiluminescent enzyme immunoassay (CLEIA) and the established CAP test for allergen-specific IgE (sIgE) has only been evaluated by a few studies. We performed such an interassay comparison using 283 Korean allergic patients with the following: asthma (18.4%), allergic rhinitis (18.4%), both asthma and allergic rhinitis (14.5%), atopic dermatitis (21.9%), and others (26.8%). We compared the sIgE detection performance of both systems for 10 major inhalant allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae, Blattela germanica, cat dander, dog hair, alder, birch, oak, ragweed, and mugwort) and four food allergens (egg white, cow milk, peanut, and shrimp). After 645 paired comparison tests, close association and significant correlation were observed between the results of both assays for most of these allergens (r=0.525-0.979, p<0.05, respectively), except for shrimp. Intermethod agreement based on sIgE detection was fair to good (74.1-100%, kappa=0.514-1.000, p<0.05, respectively) for most allergens except for B. germanica, ragweed, and shrimp. Although both assays showed good accuracy in ROC curve analysis, some minor differences were noted. IMMULITE 2000 CLEIA for sIgE detection showed fair to good intermethod correlation, association, agreement, and accuracy in comparison to the established CAP assay among Korean allergic patients. However, we should take into account the intermethod differences between both assays for clinical applications.

Influence of peanut matrix on stability of allergens in gastric-simulated digesta: 2S albumins are main contributors to the IgE reactivity of short digestion-resistant peptides.

PubMed

Prodic, I; Stanic-Vucinic, D; Apostolovic, D; Mihailovic, J; Radibratovic, M; Radosavljevic, J; Burazer, L; Milcic, M; Smiljanic, K; van Hage, M; Cirkovic Velickovic, T

2018-06-01

Most food allergens sensitizing via the gastrointestinal tract are stable proteins that are resistant to pepsin digestion, in particular major peanut allergens, Ara h 2 and Ara h 6. Survival of their large fragments is essential for sensitizing capacity. However, the immunoreactive proteins/peptides to which the immune system of the gastrointestinal tract is exposed during digestion of peanut proteins are unknown. Particularly, the IgE reactivity of short digestion-resistant peptides (SDRPs; <10 kDa) released by gastric digestion under standardized and physiologically relevant in vitro conditions has not been investigated. The aim of this study was to investigate and identify digestion products of major peanut allergens and in particular to examine IgE reactivity of SDRPs released by pepsin digestion of whole peanut grains. Two-dimensional gel-based proteomics and shotgun peptidomics, immunoblotting with allergen-specific antibodies from peanut-sensitized patients, enzyme-linked immunosorbent inhibition assay and ImmunoCAP tests, including far ultraviolet-circular dichroism spectroscopy were used to identify and characterize peanut digesta. Ara h 2 and Ara h 6 remained mostly intact, and SDRPs from Ara h 2 were more potent in inhibiting IgE binding than Ara h 1 and Ara 3. Ara h 1 and Ara h 3 exhibited sequential digestion into a series of digestion-resistant peptides with preserved allergenic capacity. A high number of identified SDRPs from Ara h 1, Ara h 2 and Ara h 3 were part of short continuous epitope sequences and possessed substantial allergenic potential. Peanut grain digestion by oral and gastric phase enzymes generates mixture of products, where the major peanut allergens remain intact and their digested peptides have preserved allergenic capacity highlighting their important roles in allergic reactions to peanut. © 2018 John Wiley & Sons Ltd.

Identification of critical amino acids in the IgE epitopes of Ric c 1 and Ric c 3 and the application of glutamic acid as an IgE blocker.

PubMed

Deus-de-Oliveira, Natalia; Felix, Shayany P; Carrielo-Gama, Camila; Fernandes, Keysson V; DaMatta, Renato Augusto; Machado, Olga L T

2011-01-01

The allergenicity of Ricinus communis L. (castor bean, Euphorbiaceae) is associated with components of its seeds and pollen. Castor bean allergy has been described not only in laboratory workers, but also in personnel working in oil processing mills, fertilizer retail, the upholstery industry and other industrial fields. In the present study, we describe the critical amino acids in the IgE-binding epitopes in Ric c 1 and Ric c 3, two major allergens of R. communis. In addition, we also investigate the cross-reactivity between castor bean and some air and food allergen extracts commonly used in allergy diagnosis. The IgE reactivity of human sera from atopic patients was screened by immune-dot blot against castor bean allergens. Allergenic activity was evaluated in vitro using a rat mast cell activation assay and by ELISA. Cross-reactivity was observed between castor bean allergens and extracts from shrimp, fish, gluten, wheat, soybean, peanut, corn, house dust, tobacco and airborne fungal allergens. We observed that treatment of rat and human sera (from atopic patients) with glutamic acid reduced the IgE-epitope interaction. The identification of glutamic acid residues with critical roles in IgE-binding to Ric c 3 and Ric c 1 support the potential use of free amino acids in allergy treatment.

Technical publication transfer test with McDonnell Aircraft Company: MIL-M-28001 (SGML) and MIL-D-28000 Class 1 (IGES)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1990-06-25

The CALS Test Network (CTN) conducted a CTN Planned Test (CPT) of several CALS standards related to the transfer of technical publication data: MIL-STD-1840A (1840A), MIL-D-28000 Class I (28000), MIL-M-28001 (28001), and MIL-D-28003 (28003). The test was conducted with the McDonnell Aircraft Company (CMAIR) of St. Louis, Missouri in accordance with part one of CTN Test Plan CTN89-TM-06 and using material from an F-15E technical manual. One focus of the test was the transfer of a moderately large volume of technical publication data. There were 9 text files, 74 Initial Graphics Exchange Specification (IGES) files, and 74 Computer Graphics Metafilemore » (CGM) files in the exchange package. A noteworthy feature of the test was its early attempt to exchange CGM data. Part one of CTN89-TM-06 called for technical publication data to be output from MCAIR's Xyvision system on 9-track magnetic tape. The data was to be in accordance with the 28001 subset of the Standard Generalized Mark-up Language (SGML) and the 28001 Document Type Definition (DTD) that conformed to MIL-M-38784B, the general style and format requirements for technical manuals. Technical illustrations in the manual were to be done in accordance with 28000 Class I (IGES) and 28003 (CGM). Part two of the test called for the test tape to be read into another technical publication system where the text would be modified and the vector illustrations would all be converted to raster, in accordance with MIL-R-28002. This part of the test is not covered in this report.« less

Patch testing and allergen-specific serum IgE and IgG antibodies in the diagnosis of canine adverse food reactions.

PubMed

Bethlehem, Simone; Bexley, Jennifer; Mueller, Ralf S

2012-02-15

Adverse food reaction (AFR) is a common differential diagnosis for pruritic dogs. The only way to diagnose AFR is an elimination diet of 6-8 weeks with a protein and a carbohydrate source not previously fed. In humans, patch testing has been shown to be a useful tool to diagnose food allergies. In veterinary medicine, serum food allergen-specific antibody testing is widely offered to identify suitable ingredients for such diets. The aim of this study was to determine sensitivity, specificity, negative and positive predictability of patch testing with and serum antibody testing for a variety of common food stuffs. Twenty-five allergic dogs underwent an elimination diet and individual rechallenge with selected food stuffs, food patch testing and serum testing for food-antigen specific IgE and IgG. Eleven clinically normal control dogs only were subjected to patch and serum testing. The sensitivity and specificity of the patch test were 96.7 and 89.0% respectively, negative and positive predictability were 99.3 and 63.0%. For IgE and IgG the sensitivity was 6.7 and 26.7%, specificity were 91.4 and 88.3%, the negative predictive values 80.7 and 83.7% and the positive predictive values were 15.4 and 34.8%. Based on these results, a positive reaction of a dog on these tests is not very helpful, but a negative result indicates that this antigen is tolerated well. We conclude that patch testing (and to a lesser degree serum testing) can be helpful in choosing ingredients for an elimination diet in a dog with suspected AFR. Copyright © 2012. Published by Elsevier B.V.

Characterization of specific anti-Candida IgM, IgA and IgE: diagnostic value in deep-seated infections.

PubMed

Aubert, D; Puygauthier-Toubas, D; Leon, P; Pignon, B; Foudrinier, F; Marnef, F; Boulant, J; Pinon, J M

1996-01-01

The proposed serological diagnosis of systemic Candida infections is based on a microplate immunocapture technique detecting IgM, IgA and IgE anti-Candida antibodies. Activity is revealed with a suspension of human erythrocytes sensitized with somatic antigen of Candida albicans, and is quantified on an automated plate reader. The sera were obtained from patients with deep-seated (n = 56) and superficial (n = 193) candidosis. We compared this immunological method with a combination of indirect immunofluorescence and co-immunoelectrodiffusion. The immunocapture method was more sensitive (80.4% vs. 48.2% with indirect immunofluorescence and 58.9% with co-immunoelectrodiffusion), and often provided the diagnosis at an earlier stage, with clear therapeutic advantages. The IgA isotype was a particularly valuable marker of deep-seated Candida infections.

Peanut flour aggregation with polyphenolic extracts derived from peanut skin inhibits IgE binding capacity and attenuates RBL-2H3 cells degranulation via MAPK signaling pathway.

PubMed

Bansode, Rishipal R; Plundrich, Nathalie J; Randolph, Priscilla D; Lila, Mary Ann; Williams, Leonard L

2018-10-15

This study investigates the anti-allergic properties of peanut skin polyphenols (PSP)-enriched peanut (PN) protein aggregates. PSP was blended with PN flour at concentrations of 5, 10, 15, 30, and 40% (w/w). Rat basophil leukemia cells (RBL-2H3) were sensitized with either anti-DNP-IgE or PN-allergic plasma followed by co-exposure to unmodified PN flour (control) or PSP-PN protein aggregates and Ca 2+ ionophore, ionomycin. Immunoblotting and staining were performed to measure the IgE binding capacity of PSP-PN aggregates. Results showed that 30% PSP-PN aggregate significantly reduced β-hexosaminidase and histamine levels by 54.2% and 49.2%, respectively compared with control. Immunoblotting results revealed 40% PSP-PN aggregates significantly decreased IgE binding by 19%. The phosphorylation of p44/42 MAPK was significantly reduced while phosphorylation of p38 MAPK and SAPK/JNK increased upon PSP-PN protein aggregate exposure to the cells. Our results show that aggregation of PSP to PN proteins reduces allergic response by inhibiting Ca 2+ -induced MAPK-dependent cell degranulation. Copyright © 2018 Elsevier Ltd. All rights reserved.

Immediate Wheal Reactivity to Autologous Sweat in Atopic Dermatitis Is Associated with Clinical Severity, Serum Total and Specific IgE and Sweat Tryptase Activity.

PubMed

Ilves, Tiina; Virolainen, Anu; Harvima, Ilkka Tapani

2016-01-01

Sweating can worsen atopic dermatitis (AD). The purpose of this work was to study the associations between reactivity to autologous sweat and the clinical severity of AD as well as investigate the possible wheal-inducing factors of sweat. Intracutaneous skin tests with autologous sweat were performed on 50 AD patients and 24 control subjects. In skin biopsies, tryptase and PAR-2 were enzyme and immunohistochemically stained. The associations between skin test reactivity and sweat histamine concentration, tryptase or chymase activity levels, tryptase or PAR-2 expression and AD clinical severity or IgE levels were investigated. The wheal reactions in the intracutaneous tests with autologous sweat were positive, weakly positive and negative in 38, 34 and 28% of the AD patients, respectively, and in 4, 46 and 50% of the healthy controls, respectively (p = 0.008). In AD, the wheal reaction was associated significantly with clinical severity, serum total and specific IgE levels and sweat tryptase activity, but not with sweat histamine and chymase. In nonlesional AD skin, the percentage of PAR-2+ mast cells (MCs) or the number of tryptase+ MCs did not differ significantly between the intracutaneous test reactivity groups. Reactivity to autologous sweat correlates with the clinical severity of AD, and tryptase may be one of the factors involved in the sweat-induced wheal. © 2016 S. Karger AG, Basel.

Testing the "toxin hypothesis of allergy": Mast cells, IgE, and innate and acquired immune responses to venoms*

PubMed Central

Tsai, Mindy; Starkl, Philipp; Marichal, Thomas; Galli, Stephen J.

2015-01-01

Summary Work in mice indicates that innate functions of mast cells, particularly degradation of venom toxins by mast cell-derived proteases, can enhance resistance to certain arthropod or reptile venoms. Recent reports indicate that acquired Th2 immune responses associated with the production of IgE antibodies, induced by Russell’s viper venom or honeybee venom, or by a component of honeybee venom, bee venom phospholipase 2 (bvPLA2), can increase the resistance of mice to challenge with potentially lethal doses of either of the venoms or bvPLA2. These findings support the conclusion that, in contrast to the detrimental effects associated with allergic Th2 immune responses, mast cells and IgE-dependent immune responses to venoms can contribute to innate and adaptive resistance to venom-induced pathology and mortality. PMID:26210895

Effects of industrial cashew nut processing on anacardic acid content and allergen recognition by IgE.

PubMed

Mattison, Christopher P; Malveira Cavalcante, Jéfferson; Izabel Gallão, Maria; Sousa de Brito, Edy

2018-02-01

Cashew nuts are important both nutritionally and industrially, but can also cause food allergies in some individuals. The present study aimed to assess the effect(s) of industrial processing on anacardic acids and allergens present in cashew nuts. Sample analyses were performed using liquid chromatography coupled with mass spectrometry, SDS-PAGE and immunoassay. The anacardic acid concentration ranged from 6.2 to 82.6mg/g during processing, and this variation was attributed to cashew nut shell liquid incorporation during storage and humidification. Dehydrated and selected samples did not significantly differ in anacardic acid content, having values similar to the raw sample. SDS-PAGE and immunoassay analysis with rabbit polyclonal sera and human IgE indicated only minor differences in protein solubility and antibody binding following processing steps. The findings indicate that appreciable amounts of anacardic acid remain in processed nuts, and that changes to cashew allergens during industrial processing may only mildly affect antibody recognition. Published by Elsevier Ltd.

Identification of Critical Amino Acids in the IgE Epitopes of Ric c 1 and Ric c 3 and the Application of Glutamic Acid as an IgE Blocker

PubMed Central

Deus-de-Oliveira, Natalia; Felix, Shayany P.; Carrielo-Gama, Camila; Fernandes, Keysson V.; DaMatta, Renato Augusto; Machado, Olga L. T.

2011-01-01

Background The allergenicity of Ricinus communis L. (castor bean, Euphorbiaceae) is associated with components of its seeds and pollen. Castor bean allergy has been described not only in laboratory workers, but also in personnel working in oil processing mills, fertilizer retail, the upholstery industry and other industrial fields. In the present study, we describe the critical amino acids in the IgE-binding epitopes in Ric c 1 and Ric c 3, two major allergens of R. communis. In addition, we also investigate the cross-reactivity between castor bean and some air and food allergen extracts commonly used in allergy diagnosis. Methodology/Principal Findings The IgE reactivity of human sera from atopic patients was screened by immune-dot blot against castor bean allergens. Allergenic activity was evaluated in vitro using a rat mast cell activation assay and by ELISA. Cross-reactivity was observed between castor bean allergens and extracts from shrimp, fish, gluten, wheat, soybean, peanut, corn, house dust, tobacco and airborne fungal allergens. We observed that treatment of rat and human sera (from atopic patients) with glutamic acid reduced the IgE-epitope interaction. Conclusions/Significance The identification of glutamic acid residues with critical roles in IgE-binding to Ric c 3 and Ric c 1 support the potential use of free amino acids in allergy treatment. PMID:21738671

HART-II: Prediction of Blade-Vortex Interaction Loading

DTIC Science & Technology

2003-09-01

14:30 (2) Improvement of DLR Rotor Aero- acoustic Code ( APSIM ) and its Valida- tion with Analytic Solution J. Yin, J. Delfs (5...of DLR Rotor Aero- acoustic Code ( APSIM ) and its Valida- tion with Analytic Solution J. Yin, J. Delfs (5) Aeroelastic Stability Analysis of...of DLR Rotor Aero- acoustic Code ( APSIM ) and its Valida- tion with Analytic Solution J. Yin, J. Delfs (5) Aeroelastic Stability Analysis of

Testing the 'toxin hypothesis of allergy': mast cells, IgE, and innate and acquired immune responses to venoms.

PubMed

Tsai, Mindy; Starkl, Philipp; Marichal, Thomas; Galli, Stephen J

2015-10-01

Work in mice indicates that innate functions of mast cells, particularly degradation of venom toxins by mast cell-derived proteases, can enhance resistance to certain arthropod or reptile venoms. Recent reports indicate that acquired Th2 immune responses associated with the production of IgE antibodies, induced by Russell's viper venom or honeybee venom, or by a component of honeybee venom, bee venom phospholipase 2 (bvPLA2), can increase the resistance of mice to challenge with potentially lethal doses of either of the venoms or bvPLA2. These findings support the conclusion that, in contrast to the detrimental effects associated with allergic type 2 (Th2) immune responses, mast cells and IgE-dependent immune responses to venoms can contribute to innate and adaptive resistance to venom-induced pathology and mortality. Copyright © 2015 Elsevier Ltd. All rights reserved.

Specific IgE to fish extracts does not predict allergy to specific species within an adult fish allergic population

PubMed Central

2014-01-01

Background Fish is an important cause of food allergy. Studies on fish allergy are scarce and in most cases limited to serological evaluation. Our objective was to study patterns of self-reported allergy and tolerance to different commonly consumed fish species and its correlation to IgE sensitization to the same species. Methods Thirty-eight adult fish allergic patients completed a questionnaire regarding atopy, age of onset and symptoms to 13 commonly consumed fish species in the Netherlands (pangasius, cod, herring, eel, hake, pollock, mackerel, tilapia, salmon, sardine, tuna, plaice and swordfish). Specific IgE to these fish extracts were analyzed by ImmunoCAP. Results Median age of onset of fish allergy was 8.5 years. Severe reactions were reported by the majority of patients (n = 20 (53%) respiratory and of these 20 patients, 6 also had cardiovascular symptoms). After diagnosis, 66% of the patients had eliminated all fish from their diet. Allergy to all species ever tried was reported by 59%. In relation to species ever tried, cod (84%) and herring (79%) were the most frequently reported culprit species while hake (57%) and swordfish (55%) were the least frequent. A positive sIgE (value ≥ 0.35 kUA/L) to the culprit species ranged between 50% (swordfish) and 100% (hake). In tolerant patients, a negative sIgE (value < 0.35 kUA/L) ranged from 0% (hake, pollock and swordfish) to 75% (sardine). For cod, the agreement between sIgE test results and reported allergy or tolerance was 82% and 25%, respectively. Sensitization to cod parvalbumin (Gad c 1) was present in 77% of all patients. Conclusion Serological cross-reactivity between fish species is frequent, but in a significant proportion of patients, clinical relevance appears to be limited to only certain species. A well-taken history or food challenge is required for discrimination between allergy to the different fish species. PMID:25225608

Specific IgE to fish extracts does not predict allergy to specific species within an adult fish allergic population.

PubMed

Schulkes, Karlijn Jg; Klemans, Rob Jb; Knigge, Lidy; de Bruin-Weller, Marjolein; Bruijnzeel-Koomen, Carla Afm; Marknell deWitt, Asa; Lidholm, Jonas; Knulst, André C

2014-01-01

Fish is an important cause of food allergy. Studies on fish allergy are scarce and in most cases limited to serological evaluation. Our objective was to study patterns of self-reported allergy and tolerance to different commonly consumed fish species and its correlation to IgE sensitization to the same species. Thirty-eight adult fish allergic patients completed a questionnaire regarding atopy, age of onset and symptoms to 13 commonly consumed fish species in the Netherlands (pangasius, cod, herring, eel, hake, pollock, mackerel, tilapia, salmon, sardine, tuna, plaice and swordfish). Specific IgE to these fish extracts were analyzed by ImmunoCAP. Median age of onset of fish allergy was 8.5 years. Severe reactions were reported by the majority of patients (n = 20 (53%) respiratory and of these 20 patients, 6 also had cardiovascular symptoms). After diagnosis, 66% of the patients had eliminated all fish from their diet. Allergy to all species ever tried was reported by 59%. In relation to species ever tried, cod (84%) and herring (79%) were the most frequently reported culprit species while hake (57%) and swordfish (55%) were the least frequent. A positive sIgE (value ≥ 0.35 kUA/L) to the culprit species ranged between 50% (swordfish) and 100% (hake). In tolerant patients, a negative sIgE (value < 0.35 kUA/L) ranged from 0% (hake, pollock and swordfish) to 75% (sardine). For cod, the agreement between sIgE test results and reported allergy or tolerance was 82% and 25%, respectively. Sensitization to cod parvalbumin (Gad c 1) was present in 77% of all patients. Serological cross-reactivity between fish species is frequent, but in a significant proportion of patients, clinical relevance appears to be limited to only certain species. A well-taken history or food challenge is required for discrimination between allergy to the different fish species.

Usefulness of basophil activation test for the diagnosis of IgE mediated hypersensitivity to tetanus toxoid vaccine.

PubMed

Herreros, Blanca; Méndez, Yesica; Feo-Brito, Francisco; Urra, José Miguel

2018-03-01

A great number of vaccinated patients develop specific anti-tetanus toxoid IgE, but usually do not undergo any adverse effect. Most of the allergic reactions to tetanus toxoid vaccine usually present with unspecific symptoms of local inflammation. In the presence of severe reactions, and in a special way if the vaccine is provided together with other drugs, it is difficult to establish which is the harmful drug responsible for IgE-mediated adverse reaction. A patient with an anaphylactic reaction after the administration of Toxoid Tetanic (TT) along with several drugs is described. All skin test were negative. The basophils activation test (BAT) in a clear way, identified TT as the allergen that triggered anaphylaxis. The results achieved demonstrates the usefulness of BAT to clarify patients with hypersensibility to tetanus toxoide when the clinic is severe and the vaccine has been administered together with other drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of acupuncture on house dust mite specific IgE, substance P, and symptoms in persistent allergic rhinitis.

PubMed

McDonald, John Leslie; Smith, Peter K; Smith, Caroline A; Changli Xue, Charlie; Golianu, Brenda; Cripps, Allan W

2016-06-01

Clinical evidence suggests that acupuncture improves symptoms in persistent allergic rhinitis, but the physiologic basis of these improvements is not well understood. A randomized, sham-controlled trial of acupuncture for persistent allergic rhinitis in adults investigated possible modulation of mucosal immune responses. A total of 151 individuals were randomized into real and sham acupuncture groups (who received twice-weekly treatments for 8 weeks) and a no acupuncture group. Various cytokines, neurotrophins, proinflammatory neuropeptides, and immunoglobulins were measured in saliva or plasma from baseline to 4-week follow-up. Statistically significant reduction in allergen specific IgE for house dust mite was seen only in the real acupuncture group, from 18.87 kU/L (95% CI, 10.16-27.58 kU/L) to 17.82 kU/L (95% CI, 9.81-25.83 kU/L) (P = .04). A mean (SE) statistically significant down-regulation was also seen in proinflammatory neuropeptide substance P (SP) 18 to 24 hours after the first treatment from 408.74 (299.12) pg/mL to 90.77 (22.54) pg/mL (P = .04). No significant changes were seen in the other neuropeptides, neurotrophins, or cytokines tested. Nasal obstruction, nasal itch, sneezing, runny nose, eye itch, and unrefreshed sleep improved significantly in the real acupuncture group (postnasal drip and sinus pain did not) and continued to improve up to 4-week follow-up. Acupuncture modulated mucosal immune response in the upper airway in adults with persistent allergic rhinitis. This modulation appears to be associated with down-regulation of allergen specific IgE for house dust mite, which this study is the first to report. Improvements in nasal itch, eye itch, and sneezing after acupuncture are suggestive of down-regulation of transient receptor potential vanilloid 1. Australian New Zealand Clinical Trials Registry Identifier: ACTRN 12610001052022. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights

Polyphenol-rich pomegranate juice reduces IgE binding to cashew nut allergens.

PubMed

Li, Yichen; Mattison, Christopher P

2018-03-01

Food allergy negatively impacts quality of life and can be life-threatening. Cashew nuts can cause severe reactions in very small amounts, and they are included in a group of foods most commonly responsible for causing food allergy. Polyphenols and polyphenol-rich juices have been demonstrated to complex with peanut allergens. Here, the interaction between cashew nut allergens and polyphenol-rich juices is evaluated biochemically and immunologically. Various juices, including pomegranate (POM), blueberry (BB), and concord grape (CG) juices, were evaluated for polyphenol content and formation of polyphenol-cashew allergen complexes. Among the various juices studied, POM juice showed a greater capacity to form complexes with cashew proteins. Dynamic light scattering (DLS) demonstrated a sharp increase in cashew protein extract particle size to around 3580 nm, and fewer cashew proteins were resolved by electrophoresis after treatment with POM juice. Immunoassays demonstrated reduced IgG and IgE binding to cashew allergens due to allergen precipitation by POM juice. These observations support the formation of complexes between polyphenol and cashew proteins that can prevent antibody recognition of cashew allergens through allergen precipitation. POM juice treatment of cashew extract effectively reduces antibody binding through allergen precipitation, and these findings could be applied to the development of less allergenic cashew nut products and oral immunotherapy. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

Evaluation of the utility of atopy patch testing, skin prick testing, and total and specific IgE assays in the diagnosis of cow's milk allergy.

PubMed

Keskin, Ozlem; Tuncer, Ayfer; Adalioglu, Gonul; Sekerel, Bulent E; Sackesen, Cansin; Kalayci, Omer

2005-05-01

Information on the utility of atopy patch testing (APT) in the diagnosis of food allergy is derived from studies of children with atopic dermatitis. To evaluate the usefulness of APT in the diagnosis of cow's milk allergy (CMA) and to determine interleukin 4 and interferon-gamma production by peripheral blood mononuclear cells. Thirty-seven children (median age, 11 months) with suspected CMA who had a variety of symptoms that involved many organ systems were evaluated using double-blind placebo-controlled food challenges (DBPCFCs), and the performances of milk specific IgE, skin prick testing (SPT), and APT were determined. To search for a possible relationship between the diagnostic tests and the TH1/TH2 immune response, we measured interferon-gamma and interleukin 4 levels in the supernatants of peripheral blood mononuclear cell cultures. Seventeen children with positive DBPCFC results and 6 with a history of anaphylaxis were diagnosed as having CMA. The combined use of APT and SPT had a sensitivity of 100% and a negative predictive value of 100% but a specificity of 50% and a positive predictive value of 76%. The addition of milk specific IgE assays to APT and SPT did not improve these values. Pattern of cytokine secretion was not associated with APT positivity or a specific response to DBPCFC. Atopy patch testing may be a useful adjunct to SPT in excluding CMA in children who have allergic manifestations other than atopic dermatitis. However, DBPCFCs are still necessary in the presence of positive test results.

A single mouse monoclonal antibody, E58 modulates multiple IgE epitopes on group 1 cedar pollen allergens

PubMed Central

Goldblum, Randall M.; Ning, Bo; Judy, Barbara. M.; Holthauzen, Luis Marcelo F.; van Bavel, Julius; Kamijo, Atsushi; Midoro-Horiuti, Terumi

2016-01-01

We recently described a dominant role for conformational epitopes on the group 1 allergen of the mountain cedar (Juniperus ashei, Cupressaceae), Jun a 1, in pollen hypersensitivity in South Central U.S.A. Since these epitopes are surface exposed and are likely to be flexible, they may be susceptible to molecular or physical perturbations. This may make Jun a 1 a potential target for new forms of therapy for cedar pollinosis. Here, we describe a mouse monoclonal antibody, termed E58, which binds to the group 1 allergens of cedar pollens from three highly populated regions of the world (central U.S.A., France and Japan). Upon binding to these allergens, E58 strongly reduces the binding of patient’s IgE antibodies to these dominant allergens. This characteristic of E58, and potentially other similar antibodies, suggests an opportunity to identify preventative or therapeutic agents that may inhibit cedar pollen sensitization or prevent the allergic reactions. PMID:27174188

Linkage analysis of idiopathic generalized epilepsy (IGE) and marker loci on chromosome 6p in families of patients with juvenile myocloni epilepsy: No evidence for an epilepsy locus in the HLA region

DOE Office of Scientific and Technical Information (OSTI.GOV)

Whitehouse, W.P.; Rees, M.; Curtis, D.

1993-09-01

Evidence for a locus (EJM1) in the HLA region of chromosome 6p predisposing to idiopathic generalized epilepsy (IGE) in the families of patients with juvenile myoclonic epilepsy (JME) has been obtained in two previous studies of separately ascertained groups of kindreds. Linkage analysis has been undertaken in a third set of 25 families including a patient with JME and at least one first-degree relative with IGE. Family members were typed for eight polymorphic loci on chromosome 6p: F13A, D6889, D6S109, D6S105, D6S10, C4B, DQA1/A2, and TCTE1. Pairwise and multipoint linkage analysis was carried out assuming autosomal dominant and autosomal recessivemore » inheritance and age-dependent high or low penetrance. No significant evidence in favor of linkage was obtained at any locus. Multipoint linkage analysis generated significant exclusion data (lod score < -2.0) at HLA and for a region 10-30 cM telomeric to HLA, the extent of which varied with the level of penetrance assumed. These observations indicate that genetic heterogeneity exists within this epilepsy phenotype. 39 refs., 4 figs., 2 tabs.« less

A nonallergenic birch pollen allergy vaccine consisting of hepatitis PreS-fused Bet v 1 peptides focuses blocking IgG toward IgE epitopes and shifts immune responses to a tolerogenic and Th1 phenotype.

PubMed

Marth, Katharina; Breyer, Isabella; Focke-Tejkl, Margarete; Blatt, Katharina; Shamji, Mohamed H; Layhadi, Janice; Gieras, Anna; Swoboda, Ines; Zafred, Domen; Keller, Walter; Valent, Peter; Durham, Stephen R; Valenta, Rudolf

2013-04-01

Allergen-specific immunotherapy is the only allergen-specific and disease-modifying treatment for allergy. The construction and characterization of a vaccine for birch pollen allergy is reported. Two nonallergenic peptides, PA and PB, derived from the IgE-reactive areas of the major birch pollen allergen Bet v 1 were fused to the hepatitis B surface protein, PreS, in four recombinant fusion proteins containing different numbers and combinations of the peptides. Fusion proteins expressed in Escherichia coli and purified to homogeneity showed a lack of IgE reactivity and allergenic activity when tested with sera and basophils from patients allergic to birch pollen. Compared to Bet v 1 allergen, peptides PA and PB showed reduced T cell activation in PBMCs from allergic patients, whereas PreS fusion proteins induced less IL-5 and more IL-10 and IFN-γ. Immunization of rabbits with the fusion proteins, in particular with a PreS fusion protein 2PAPB-PreS, containing two copies of each peptide, induced high levels of IgG Abs against the major IgE-reactive site on Bet v 1 and related allergens. These IgG Abs inhibited allergic patients' IgE binding to Bet v 1 better than did IgG induced by immunization with complete Bet v 1. Furthermore, 2PAPB-PreS-induced IgG inhibited Bet v 1-induced basophil activation in allergic patients and CD23-facilitated allergen presentation. Our study exemplifies novel beneficial features for a PreS carrier-based peptide vaccine for birch pollen, which, in addition to the established reduction in allergenic activity, include the enhanced focusing of blocking Ab responses toward IgE epitopes, immunomodulatory activity, and reduction of CD23-facilitated allergen presentation.

A Nonallergenic Birch Pollen Allergy Vaccine Consisting of Hepatitis PreS–Fused Bet v 1 Peptides Focuses Blocking IgG toward IgE Epitopes and Shifts Immune Responses to a Tolerogenic and Th1 Phenotype

PubMed Central

Marth, Katharina; Breyer, Isabella; Focke-Tejkl, Margarete; Blatt, Katharina; Shamji, Mohamed H.; Layhadi, Janice; Gieras, Anna; Swoboda, Ines; Zafred, Domen; Keller, Walter; Valent, Peter; Durham, Stephen R.; Valenta, Rudolf

2014-01-01

Allergen-specific immunotherapy is the only allergen-specific and disease-modifying treatment for allergy. The construction and characterization of a vaccine for birch pollen allergy is reported. Two nonallergenic peptides, PA and PB, derived from the IgE-reactive areas of the major birch pollen allergen Bet v 1 were fused to the hepatitis B surface protein, PreS, in four recombinant fusion proteins containing different numbers and combinations of the peptides. Fusion proteins expressed in Escherichia coli and purified to homogeneity showed a lack of IgE reactivity and allergenic activity when tested with sera and basophils from patients allergic to birch pollen. Compared to Bet v 1 allergen, peptides PA and PB showed reduced T cell activation in PBMCs from allergic patients, whereas PreS fusion proteins induced less IL-5 and more IL-10 and IFN-γ. Immunization of rabbits with the fusion proteins, in particular with a PreS fusion protein 2PAPB-PreS, containing two copies of each peptide, induced high levels of IgG Abs against the major IgE-reactive site on Bet v 1 and related allergens. These IgG Abs inhibited allergic patients’ IgE binding to Bet v 1 better than did IgG induced by immunization with complete Bet v 1. Furthermore, 2PAPB-PreS–induced IgG inhibited Bet v 1–induced basophil activation in allergic patients and CD23-facilitated allergen presentation. Our study exemplifies novel beneficial features for a PreS carrier–based peptide vaccine for birch pollen, which, in addition to the established reduction in allergenic activity, include the enhanced focusing of blocking Ab responses toward IgE epitopes, immunomodulatory activity, and reduction of CD23-facilitated allergen presentation. PMID:23440415

Evaluation of Food Allergy in Children by Skin Prick Tests with Commercial Extracts and Fresh Foods, Specific IgE and, Open Oral Food Challenge-Our Five Years Experience in Food Allergy Work-up.

PubMed

Zivanovic, Mirjana; Atanasković-Marković, Marina; Medjo, Biljana; Gavrović-Jankulović, Marija; Smiljanić, Katarina; Tmušić, Vladimir; Djurić, Vojislav

2017-04-01

IgE- mediated food allergy affects 6-8% of children. Our study aimed to define the correlations between the results obtained with skin prick tests (SPTs) using commercial extracts and fresh foods, and the correlations between these result and those obtained with specific IgE (sIgE) and/ or challenge. Children aged from 2 months to 6 years were recruited prospectively. Overall 571 children were positive to one food. In all children we performed  SPT using commercial extracts of suspected food and fresh foods and sIgE. If SPT and sIgE test results did not correspond to the history, we performed open oral food challenge. Sensitivity of SPT with commercial extracts for all tested food was poor (3-35%), while  sensitivity of fresh food skin prick tests (FFSPT) was excellent (50-100%), and showed correlation with open oral food challenge (p<0.001). Our results suggest that fresh food extracts are more effective in detecting sensitization and with levels of sIgE greater than class 3 could predict clinical reactivity, without the need for potentially hazardous food challenges.

A liver-X-receptor ligand, T0901317, attenuates IgE production and airway remodeling in chronic asthma model of mice.

PubMed

Shi, Ying; Xu, Xiantao; Tan, Yan; Mao, Shan; Fang, Surong; Gu, Wei

2014-01-01

The liver-X-receptors have shown anti-inflammatory ability in several animal models of respiratory disease. Our purpose is to investigate the effect of LXR ligand in allergen-induced airway remodeling in mice. Ovalbumin-sensitized mice were chronically challenged with aerosolized ovalbumin for 8 weeks. Some mice were administered a LXR agonist, T0901317 (12.5, 25, 50 mg/kg bodyweight) before challenge. Then mice were evaluated for airway inflammation, airway hyperresponsiveness and airway remodeling. T0901317 failed to attenuate the inflammatory cells and Th2 cytokines in bronchoalveolar lavage fluid. But the application of T0901317 reduced the thickness of airway smooth muscle and the collagen deposition. Meanwhile, T0901317 treatment evidently abolished the high level of OVA-specific IgE, TGF-β1 and MMP-9 in lung. So LXRs may attenuate the progressing of airway remodeling, providing a potential treatment of asthma.

Specific IgE to peanut 2S albumin Ara h 7 has a discriminative ability comparable to Ara h 2 and 6.

PubMed

Blankestijn, M A; Otten, H G; Suer, W; Weimann, A; Knol, E F; Knulst, A C

2018-01-01

Little is known on the clinical relevance of peanut 2S albumin Ara h 7. To investigate the discriminative ability of Ara h 7 in peanut allergy and assess the role of cross-reactivity between Ara h 2, 6 and Ara h 7 isoforms. Sensitization to recombinant peanut storage proteins Ara h 1, 2, 3, 6, and 7 was assessed using a line blot in sera from 40 peanut-tolerant and 40 peanut-allergic patients, based on food challenge outcome. A dose-dependent ELISA inhibition experiment was performed with recombinant Ara h 2, 6 and Ara h 7 isoforms. For Ara h 7.0201, an area under the ROC curve was found of 0.83, comparable to Ara h 2 (AUC 0.81) and Ara h 6 (AUC 0.85). Ara h 7 intensity values strongly correlated with those from Ara h 2 and 6 (r s = 0.81). Of all patients sensitized to 2S albumins Ara h 2, 6, or 7, the majority was co-sensitized to all three (n = 24, 68%), although mono-sensitization to either 2S albumin was also observed in selected patients (Ara h 2: n = 6, 17%; Ara h 6: n = 2, 6%; Ara h 7: n = 2, 6%). Binding to Ara h 7.0101 could be strongly inhibited by Ara h 7.0201, but not the other way around. Specific IgE against Ara h 7.0201 has a predictive ability for peanut allergy similar to Ara h 2 and 6 and possesses unique IgE epitopes as well as epitopes shared between the other Ara h 7 isoform and Ara h 2 and 6. While co-sensitization to all three 2S albumins is most common, mono-sensitization to either Ara h 2, 6, or 7 occurs in selected patients, leading to a risk of misdiagnosis when testing for a single 2S albumin. © 2017 John Wiley & Sons Ltd.

Improved recombinant Api m 1- and Ves v 5-based IgE testing to dissect bee and yellow jacket allergy and their correlation with the severity of the sting reaction.

PubMed

Šelb, J; Kogovšek, R; Šilar, M; Košnik, M; Korošec, P

2016-04-01

No study has assessed the diagnostic sensitivity of rApi m 1 and rVes v 5 on Immulite testing system. To compare the diagnostic sensitivity of commercially available venom recombinant allergens between the currently available immunoassays [ImmunoCAP (CAP) and Immulite (LITE)] and establish their correlation with the severity of the sting reaction. This study evaluated 95 bee venom and 110 yellow jacket venom-allergic subjects. We measured the levels of sIgE to rApi m 1, rVes v 5 (LITE and CAP), rApi m 2 (LITE), rVes v 1 (CAP) and total IgE (CAP). Forty-nine healthy subjects served as controls. The diagnostic sensitivity of rApi m 1 and rVes v 5 was significantly higher with the LITE than with the CAP system (71% vs. 88% and 82% vs. 93%). The specificity of both assays for both allergens was between 94% and 98%. Twenty-nine patients that tested negative for rApi m 1 or rVes v 5 with CAP were positive with LITE, but none of the patients that tested negative with LITE were positive with CAP. The positive values of rApi m 1 and rVes v 5 were on average 2.7 and 2.3 times higher, with the LITE than with the CAP system. The combination of rApi m 1 and rApi m 2 (LITE) and the combination of rVes v 5 (LITE) and rVes v 1 (CAP) almost matched the sensitivity of native venoms (95% and 97%, respectively), whereas the diagnostic sensitivity of the combination of rVes v 5 and rVes v 1 (CAP) did not reach the sensitivity of rVes v 5 (LITE) alone (90% vs. 93%). IgE levels to venom recombinants and total IgE did not correlate with the severity of sting reaction. The use of rApi m 1 and rVes v 5 with the LITE system significantly enhanced diagnostic utility of venom recombinants and should improve the dissection of bee and yellow jacket venom allergy. © 2015 John Wiley & Sons Ltd.

IgE sensitization to food allergens and airborne allergens in relation to biomarkers of type 2 inflammation in asthma.

PubMed

Patelis, A; Alving, K; Middelveld, R; James, A; Ono, J; Ohta, S; Izuhara, K; Borres, M P; Forsberg, B; Janson, C; Malinovschi, A

2018-05-10

We have recently reported that sensitization to food allergens and sensitization to airborne allergens had independent associations with increased fraction of exhaled nitric oxide (FeNO) and blood eosinophils in middle-aged adults and in young subjects with asthma. To investigate the relation between IgE sensitization and several type 2 inflammation biomarkers in adult asthmatics. FeNO, urinary eosinophil-derived neurotoxin (U-EDN), serum eosinophil cationic protein (S-ECP) and periostin were measured in 396 asthmatics, aged 17-76 years, from the Swedish GA2LEN study. Sensitization to airborne allergens was examined with skin prick tests (≥3 mm wheal) and sensitization to food allergens with measurement of specific IgE (≥0.35 kU/L). Asthmatics sensitized to food allergens had higher FeNO, 22.3 ppb (18.6, 26.7) vs 16.1 ppb (14.2, 18.2) (P = .005), S-ECP, 17.7 mg/L (14.8, 21.1) vs 12.8 mg/L (10.9, 14.9) (P = .01), and periostin, 73.7 (67.5, 80.3) ng/mL vs 59.9 (55.8, 64.2) ng/mL (P = .003), than non-sensitized subjects. Periostin levels in this group were also significantly higher than in the group sensitized only to airborne allergens (P = .01). Sensitization to food allergens related independently to FeNO (P = .02), S-ECP (P = .006) and periostin (P = .004), whereas sensitization only to airborne allergens related only to FeNO (P = .02) after adjustments for age, sex, height, weight and smoking history. FeNO correlated weakly with S-ECP (r = .17, P < .001), periostin (r = .19, P < .001) and U-EDN (0.16, P < .001). S-ECP also correlated weakly with U-EDN (r = .12, P = .02). None of the correlations between the remaining pairs of markers of type 2 inflammation were significant. Sensitization to food allergens related to several local and systemic type 2 inflammation markers, such as FeNO, S-ECP and periostin. Assessing the profile of allergic sensitization, including to food allergens, might improve the understanding and

Cross-reactions vs co-sensitization evaluated by in silico motifs and in vitro IgE microarray testing.

PubMed

Pfiffner, P; Stadler, B M; Rasi, C; Scala, E; Mari, A

2012-02-01

Using an in silico allergen clustering method, we have recently shown that allergen extracts are highly cross-reactive. Here we used serological data from a multi-array IgE test based on recombinant or highly purified natural allergens to evaluate whether co-reactions are true cross-reactions or co-sensitizations by allergens with the same motifs. The serum database consisted of 3142 samples, each tested against 103 highly purified natural or recombinant allergens. Cross-reactivity was predicted by an iterative motif-finding algorithm through sequence motifs identified in 2708 known allergens. Allergen proteins containing the same motifs cross-reacted as predicted. However, proteins with identical motifs revealed a hierarchy in the degree of cross-reaction: The more frequent an allergen was positive in the allergic population, the less frequently it was cross-reacting and vice versa. Co-sensitization was analyzed by splitting the dataset into patient groups that were most likely sensitized through geographical occurrence of allergens. Interestingly, most co-reactions are cross-reactions but not co-sensitizations. The observed hierarchy of cross-reactivity may play an important role for the future management of allergic diseases. © 2011 John Wiley & Sons A/S.

Transiently increased IgE responses in infants and pre-schoolers receiving only acellular Diphtheria-Pertussis-Tetanus (DTaP) vaccines compared to those initially receiving at least one dose of cellular vaccine (DTwP) - Immunological curiosity or canary in the mine?

PubMed

Holt, Patrick G; Snelling, Tom; White, Olivia J; Sly, Peter D; DeKlerk, Nicholas; Carapetis, Jonathan; Biggelaar, Anita Van Den; Wood, Nicholas; McIntyre, Peter; Gold, Michael

2016-07-29

Several previous studies have highlighted the strong Th2-polarising and IgE-promoting activity of the DTaP vaccine, but there is no evidence that this has pathological consequences and accordingly there is no current interest amongst vaccine developers in reformulating DTaP to attenuate these properties. In light of an apparent resurgence in pertussis in many countries, and emerging evidence from other areas of paediatric immunology of IgE-mediated interference with host defence mechanisms, this issue requires more detailed clarification. We have re-evaluated the impact of DTaP-only versus mixed DTwP/DTaP vaccination on Th2-dependent "bystander" IgE responses in three cohorts of children under different priming conditions, encompassing both vaccine-targeted and unrelated antigens including food allergens. We confirm the generalised IgE-trophic activity of the DTaP vaccine in pre-schoolers and demonstrate similar (albeit transient) effects in infants. We additionally demonstrate that use of an alternative mixed infant priming schedule encompassing an initial dose of DTwP significantly attenuates this property. Central to our interpretation of these findings are studies demonstrating: (i) mixed DTwP/DTaP priming improves resistance to pertussis disease and attenuates the IgE-stimulatory component of long term vaccine-specific memory; (ii) IgE-mediated mechanisms can interfere with innate antiviral immunity and accordingly exacerbate airway symptoms in infected children. These observations, taken together with the data presented here, suggest a plausible mechanistic link between baseline pertussis-specific IgE titres in DTaP vaccinees and susceptibility to pertussis disease, which merits testing. Retrospective IgE analyses on sera collected from children at the time of presentation with pertussis could resolve this issue. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identifications of inhibitors of IgE production by human lymphocytes isolated from 'Cha Chuukanbohon Nou 6' tea leaves.

PubMed

Honma, Daiki; Tagashira, Motoyuki; Kanda, Tomomasa; Maeda-Yamamoto, Mari

2010-01-15

Tea (Camellia sinensis L.) is consumed all over the world and in especially large quantities in Japan and China, where it has been used not only as a daily beverage but also for medicinal purposes for thousands of years. Tea has been found to exhibit various bioregulatory activities, including antiallergic, anticarcinogenic, antimetastatic, antioxidative, antihypertensive, antihypercholesterolemic, anti-dental caries and antibacterial effects, and to influence intestinal flora. Cha Chuukanbohon Nou 6 is a tea cultivar improved by the National Institute of Vegetable and Tea Science (NIVTS) in Japan. On comparing chemical constituents of 11 varieties of tea leaves by high-performance liquid chromatography, we found two new major compounds in Cha Chuukanbohon Nou 6. Nuclear magnetic resonance spectroscopy revealed these compounds to be theogallin and 1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-beta-D-glucopyranose. The two were similar in chemical structure to strictinin, an inhibitor of immunoglobulin (Ig) production. Thus their effects on the production of Igs by peripheral blood lymphocytes were tested. Both compounds, like strictinin, inhibited IgE production. The results suggest Cha Chuukanbohon Nou 6 to be the basis of an antiallergic beverage. Copyright (c) 2009 Society of Chemical Industry.

Molecular Typing of Staphylococcus aureus Isolated from Patients with Autosomal Dominant Hyper IgE Syndrome

PubMed Central

Sastalla, Inka; Williams, Kelli W.; Anderson, Erik D.; Myles, Ian A.; Reckhow, Jensen D.; Espinoza-Moraga, Marlene; Freeman, Alexandra F.; Datta, Sandip K.

2017-01-01

Autosomal dominant hyper IgE syndrome (AD-HIES) is a primary immunodeficiency caused by a loss-of-function mutation in the Signal Transducer and Activator of Transcription 3 (STAT3). This immune disorder is clinically characterized by increased susceptibility to cutaneous and sinopulmonary infections, in particular with Candida and Staphylococcus aureus. It has recently been recognized that the skin microbiome of patients with AD-HIES is altered with an overrepresentation of certain Gram-negative bacteria and Gram-positive staphylococci. However, these alterations have not been characterized at the species- and strain-level. Since S. aureus infections are influenced by strain-specific expression of virulence factors, information on colonizing strain characteristics may provide insights into host-pathogen interactions and help guide management strategies for treatment and prophylaxis. The aim of this study was to determine whether the immunodeficiency of AD-HIES selects for unique strains of colonizing S. aureus. Using multi-locus sequence typing (MLST), protein A (spa) typing, and PCR-based detection of toxin genes, we performed a detailed analysis of the S. aureus isolates (n = 13) found on the skin of twenty-one patients with AD-HIES. We found a low diversity of sequence types, and an abundance of strains that expressed methicillin resistance, Panton-Valentine leukocidin (PVL), and staphylococcal enterotoxins K and Q (SEK, SEQ). Our results indicate that patients with AD-HIES may often carry antibiotic-resistant strains that harbor key virulence factors. PMID:28587312

LC-MS/MS quantification of next-generation biotherapeutics: a case study for an IgE binding Nanobody in cynomolgus monkey plasma.

PubMed

Sandra, Koen; Mortier, Kjell; Jorge, Lucie; Perez, Luis C; Sandra, Pat; Priem, Sofie; Poelmans, Sofie; Bouche, Marie-Paule

2014-05-01

Nanobodies(®) are therapeutic proteins derived from the smallest functional fragments of heavy chain-only antibodies. The development and validation of an LC-MS/MS-based method for the quantification of an IgE binding Nanobody in cynomolgus monkey plasma is presented. Nanobody quantification was performed making use of a proteotypic tryptic peptide chromatographically enriched prior to LC-MS/MS analysis. The validated LLOQ at 36 ng/ml was measured with an intra- and inter-assay precision and accuracy <20%. The required sensitivity could be obtained based on the selectivity of 2D LC combined with MS/MS. No analyte specific tools for affinity purification were used. Plasma samples originating from a PK/PD study were analyzed and compared with the results obtained with a traditional ligand-binding assay. Excellent correlations between the two techniques were obtained, and similar PK parameters were estimated. A 2D LC-MS/MS method was successfully developed and validated for the quantification of a next generation biotherapeutic.

Impact of allergic reactions on food-specific IgE concentrations and skin test results

PubMed Central

Sicherer, Scott H.; Wood, Robert A.; Vickery, Brian P.; Perry, Tamara T; Jones, Stacie M.; Leung, Donald Y. M.; Blackwell, Beth; Dawson, Peter; Burks, A. Wesley; Lindblad, Robert; Sampson, Hugh A.

2015-01-01

Background Although there is concern that food allergic reactions may negatively affect the natural history of food allergy, the impact of reactions on food-specific IgE (sIgE) or skin prick tests is unknown. Objective To measure the effects of allergic reactions on SPT wheal size and sIgE concentrations to milk, egg and peanut. Methods Participants included 512 infants with likely milk or egg allergy enrolled in a multi-center observational study. Changes in sIgE and SPT to milk, egg, and peanut were measured before and after oral food challenge (OFC) or accidental exposure for 377 participants. Results Median age of the cohort at time of analysis was 8.5 years (67% male). There were no statistically significant changes in sIgE or SPT after positive OFC to milk, egg, or peanut (n=20-27 for each food). Change in sIgE and SPT was measured after 446 and 453 accidental exposure reactions, respectively. Median change in sIgE decreased by 0.33 kUA/L (p<.01) after milk and by 0.34 (p<.01) after egg reactions; but no other statistically significant changes in sIgE or SPT were observed for milk, egg, or peanut. Limiting analysis to only participants with diagnostic testing done within 6 months of an accidental exposure reaction, peanut SPT increased 1.75 mm (p<.01), but a significant increase was not noted when all participants with testing done within 12 months were considered. Conclusions The results suggest that reactions from OFCs and accidental exposure are not associated with increases in sensitization among children allergic to milk, egg or peanut. PMID:26718150

The influence of a residual group in low-molecular-weight allergoids of Artemisia vulgaris pollen on their allergenicity, IgE- and IgG-binding properties.

PubMed

Cirković, T; Gavrović-Jankulović, M; Prisić, S; Jankov, R M; Burazer, L; Vucković, O; Sporcić, Z; Paranos, S

2002-11-01

Reaction of epsilon-amino groups of lysine with potassium cyanate, maleic, or succinic anhydride leads to allergoids of low molecular weight. No study has been performed to compare their properties and investigate the influence of a residual group on allergenicity and human IgE- and IgG-binding of these derivatives. Allergoids of a pollen extract of Artemisia vulgaris were obtained by means of potassium cyanate, and succinic and maleic anhydride. Biochemical properties were investigated by determination of amino groups, enzyme activity, isoelectric focusing IEF and SDS-PAGE. IgE- and IgG-binding was determined using immunoblots and ELISA inhibition. Allergenicity was investigated by skin prick tests (SPT) on a group of 52 patients, of which 6 were control subjects, 30 were patients with no previous immunotherapy (IT), and 16 were patients undergoing immunotherapy. The same degree of amino-group modification (more than 85%), residual enzyme activity (less then 15%), IEF, and SDS-PAGE pattern were noted. In the immunoblots of IgE-binding, there was more pronounced reduction in the succinyl and maleyl derivatives than in the carbamyl one. IgG-binding was less affected by carbamylation than by acid anhydride modification. The SPT showed that the succinylated derivative had the most reduced allergenicity (98% showed a reduced wheal diameter when tested with the succinyl derivative, 87% with the maleyl allergoid, and 83% with the carbamyl allergoid). The most significant difference among allergoids could be seen in the group of patients with high skin reactivity (83% of patients showed no reaction to the succinyl derivative when compared to the value of 28% for the carbamyl derivative or 22% for the maleyl derivative). According to our results, all three modification procedures yielded allergoids with a similar extent of modification. No single biochemical parameter investigated in the study could predict the degree of reduced allergenicity in vivo. The most reduced

Regulation by CD45 of the tyrosine phosphorylation of high affinity IgE receptor beta- and gamma-chains.

PubMed

Adamczewski, M; Numerof, R P; Koretzky, G A; Kinet, J P

1995-04-01

Previous studies using tyrosine phosphatase inhibitors have implicated tyrosine phosphatases in the signal transduction pathway initiated by aggregation of Fc epsilon RI, the high affinity receptor for IgE. To define more precisely a role for the tyrosine phosphatase CD45 in Fc epsilon RI-mediated signaling, we have transfected the three subunits of Fc epsilon RI into wild-type Jurkat and a CD45-deficient Jurkat derivative. Here we demonstrate that CD45 is necessary for the initiation of calcium flux through the transfected Fc epsilon RI. In contrast to the effect of phosphatase inhibitors, the tyrosine phosphorylation levels of beta and gamma after aggregation of Fc epsilon RI are surprisingly reduced, relative to wild-type Jurkat, in the CD45-deficient cells. After reconstitution of the CD45-deficient cells with a chimeric molecule containing the cytoplasmic phosphatase domains of CD45, both the base line and activation-induced tyrosine phosphorylation levels are increased. By examining Lck autophosphorylation, we find that Fc epsilon RI aggregation induces an increase in Lck enzymatic activity only in wild-type Jurkat and the CD45-deficient Jurkat reconstituted with chimeric CD45. This regulation of src-family tyrosine kinase activity may be the means by which CD45 controls aggregation-induced receptor phosphorylation.

Reactivity of IgE to the allergen hyaluronidase from Polybia paulista (Hymenoptera, Vespidae) venom.

PubMed

Justo Jacomini, Débora Laís; Gomes Moreira, Susana Margarida; Campos Pereira, Franco Dani; Zollner, Ricardo de Lima; Brochetto Braga, Márcia Regina

2014-05-01

To date, there are no allergenic extracts or components available in Brazil to diagnosis and treatment of patients with venom allergy from social wasp (Vespidae Family; Polistinae Subfamily) despite of the great number of existing species. We evaluated the immunogenic potential of the Hyal recombinant protein (Pp-Hyal-rec) which was expressed in an insoluble form in comparison with the allergenic native protein (Pp-Hyal-nat) for recognition of immunoglobulin E (IgE) in the serum of allergic patients to venom of the endemic social wasp Polybia paulista from São Paulo State, Brazil. Hyal cDNA from the venom of the social wasp P. paulista (Pp-Hyal) (GI: 302201582) was cloned into the expression vector pET-28a in Escherichia coli DE3 (BL21) cells. Solubilization and purification of Pp-Hyal-rec from inclusion bodies were performed using Ni(2+) affinity chromatography (Ni-NTA-Agarose) under denaturing conditions. Both the native (Pp-Hyal-nat) and the recombinant (Pp-Hyal-rec) purified allergens were used for Western blotting to assess the levels of Pp-Hyal-IgE specific in the serum of 10 patients exclusively reactive to the venom of the social wasp P. paulista. The immune sera specifically recognized the band corresponding to the Pp-Hyal-rec protein (40 kDa) at a higher intensity than the native allergen (39 kDa). The sera recognized other proteins in P. paulista crude venom extract to a lesser extent, likely corresponding to other venom allergens such as phospholipase (34 kDa), Antigen 5 (25 kDa), and proteases. The recognition pattern of the immune sera to the Pp-Hyal-rec allergen strongly suggests that this recombinant antigen could be used for developing a diagnostic allergy test as well as for specific immunotherapy (IT). Copyright © 2014 Elsevier Ltd. All rights reserved.

[Effect on chronic urticaria and serum IL-4 and IgE in the patients treated with moving cupping therapy and autohemotherapy with acupoint inection].

PubMed

Zhang, Wan-Rong; Lang, Na

2014-12-01

To explore the clinical efficacy and effect mechanism on chronic urticaria treated with moving cupping therapy combined with autohemotherapy with acupaint injection for desensitization at acupoints. One hundred and four patients of chronic urticaria were randomized into a comprehensive therapy group and a medication group, 52 cases in each one. In the comprehensive therapy group, the moving cupping therapy along the governor vessel and bladder meridian of foot-taiyang was applied combined with autohemotherapy with acupaint injection for desensitization at acupoints. The self-venous blood was injected at bilateral Quchi (LI 11) and Zusanli (ST 36), 1 mL at each acupoint, once every 3 days. In the medication group, cetirizine tablets, 10 mg were prescribed for oral administration, once every day, and the compound dexamethasone acetate cream was used externally, once to twice a day. The clinical efficacy: was observed in 30 days of treatment in the two groups. The changes of serum interleukin 4 (IL-4) and immunoglobulin E (Ig E) before and after treatment were observed. The recurrence rate was compared between the two groups in 3 months after treatment. The cured and markedly effective rate was 90.4% (47/52) in the comprehensive therapy group, which was higher obviously than 78.8% (41/52, P < 0.05) in the medication group. The levels of serum IL-4 and IgE were reduced in the patients of the two groups, indicating the significant difference in comparison before and after treatment (all P < 0.01) and the reducing degree in the comprehensive therapy group was much more significant than that in the medicine group (both P < 0.01). The recurrence rate was 19. 1% (9/47) in the comprehensive therapy group in the 3-month follow-up after treatment, and apparently lower than 51.2% (21/41, P < 0.01). The moving cupping therapy combined with autohemotherapy with acupaint injection for desensitization at acupoints achieves the better efficacy on chronic urticaria compared with the

The diagnostic value of specific IgE to Ara h 2 to predict peanut allergy in children is comparable to a validated and updated diagnostic prediction model.

PubMed

Klemans, Rob J B; Otte, Dianne; Knol, Mirjam; Knol, Edward F; Meijer, Yolanda; Gmelig-Meyling, Frits H J; Bruijnzeel-Koomen, Carla A F M; Knulst, André C; Pasmans, Suzanne G M A

2013-01-01

A diagnostic prediction model for peanut allergy in children was recently published, using 6 predictors: sex, age, history, skin prick test, peanut specific immunoglobulin E (sIgE), and total IgE minus peanut sIgE. To validate this model and update it by adding allergic rhinitis, atopic dermatitis, and sIgE to peanut components Ara h 1, 2, 3, and 8 as candidate predictors. To develop a new model based only on sIgE to peanut components. Validation was performed by testing discrimination (diagnostic value) with an area under the receiver operating characteristic curve and calibration (agreement between predicted and observed frequencies of peanut allergy) with the Hosmer-Lemeshow test and a calibration plot. The performance of the (updated) models was similarly analyzed. Validation of the model in 100 patients showed good discrimination (88%) but poor calibration (P < .001). In the updating process, age, history, and additional candidate predictors did not significantly increase discrimination, being 94%, and leaving only 4 predictors of the original model: sex, skin prick test, peanut sIgE, and total IgE minus sIgE. When building a model with sIgE to peanut components, Ara h 2 was the only predictor, with a discriminative ability of 90%. Cutoff values with 100% positive and negative predictive values could be calculated for both the updated model and sIgE to Ara h 2. In this way, the outcome of the food challenge could be predicted with 100% accuracy in 59% (updated model) and 50% (Ara h 2) of the patients. Discrimination of the validated model was good; however, calibration was poor. The discriminative ability of Ara h 2 was almost comparable to that of the updated model, containing 4 predictors. With both models, the need for peanut challenges could be reduced by at least 50%. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Discordance between aeroallergen specific serum IgE and skin testing in children younger than 4 years.

PubMed

de Vos, Gabriele; Nazari, Ramin; Ferastraoaru, Denisa; Parikh, Purvi; Geliebter, Rebecca; Pichardo, Yikania; Wiznia, Andrew; Rosenstreich, David

2013-06-01

Atopic sensitization to aeroallergens in early life has been found to be a strong risk factor for the development of persisting asthma in young children with recurrent wheeze. To assess the yield of skin prick test (SPT) compared with allergen specific serum IgE (sIgE) testing at identifying aeroallergen sensitization in atopic children younger than 4 years. Concordance between SPT and allergen-specific sIgE testing for 7 common aeroallergens was analyzed in 40 atopic inner-city children 18 to 48 months of age (mean [SD], 36 [9] months) with recurrent wheezing and family history of asthma and/or eczema. In 80% of children one or more allergen sensitizations would have been missed if only SPT had been performed, and in 38% of children one or more sensitizations would have been missed if only sIgE testing had been performed. Agreement between the SPT and sIgE test was fair for most allergens (κ = -0.04 to 0.50), as was correlation between sIgE levels and SPT grade (ρ = 0.21 to 0.55). Children with high total sIgE (≥300 kU/L) were more likely to have positive sIgE test results, with negative corresponding SPT results (P = .02). Our study revealed a significant discordance between allergen-specific SPT and sIgE testing results for common aeroallergens, suggesting that both SPT and sIgE testing should be performed when diagnosing allergic sensitization in young children at high risk of asthma. clinicaltrials.gov Identifier: NCT01028560. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Allergenic components of a novel food, Micronesian nut Nangai (Canarium indicum), shows IgE cross-reactivity in pollen allergic patients.

PubMed

Sten, Eva; Stahl Skov, P; Andersen, S B; Torp, A M; Olesen, A; Bindslev-Jensen, U; Poulsen, L K; Bindslev-Jensen, C

2002-05-01

New foods may present a risk for food hypersensitive patients. Several examples exist of allergic reactions caused by cross-reactive plant-derived foods, and new foods should be scrutinised before introducing them to the market. We have evaluated the clinical and serological relevance of cross-reactivity between Nangai and pollen allergens. Cross-reactivity was examined with Maxisorp RAST (radioallergosorbent test), RAST inhibition and Western blot, using sera from patients allergic to grass, birch and mugwort pollen. None of the patients reported having seen or eaten Nangai previously. To determine the biological and clinical relevance of the cross-reactivity, histamine release (HR) test, skin prick test (SPT) and food challenge were used. There was prevalence for reactivity against Nangai in the group of pollen allergic patients. This cross-reactivity seems to be related--at least in part--to carbohydrate epitopes. Three out of 12 patients tested with Nangai were positive upon open challenge, but using double blind placebo controlled food challenge (DBPCFC) this could not be confirmed in two patients. The biological effects of Nangai on allergic patients were confirmed using HR and SPT. The Nangai specific IgE found among pollen allergic patients addresses the need for control of new or changed foods before introduction to the market.

Impact of Allergic Reactions on Food-Specific IgE Concentrations and Skin Test Results.

PubMed

Sicherer, Scott H; Wood, Robert A; Vickery, Brian P; Perry, Tamara T; Jones, Stacie M; Leung, Donald Y M; Blackwell, Beth; Dawson, Peter; Burks, A Wesley; Lindblad, Robert; Sampson, Hugh A

2016-01-01

Although there is concern that food allergy reactions may negatively affect the natural history of food allergy, the impact of reactions on food-specific IgE (sIgE) levels or skin prick test (SPT) wheal size is unknown. To measure the effects of allergic reactions on SPT wheal size and sIgE concentrations to milk, egg, and peanut. Participants included 512 infants with likely milk or egg allergy enrolled in a multicenter observational study. Changes in sIgE level and SPT wheal size to milk, egg, and peanut were measured before and after oral food challenge (OFC) or accidental exposure for 377 participants. The median age of the cohort at the time of analysis was 8.5 years (67% males). There were no statistically significant changes in sIgE level or SPT wheal size after positive OFC to milk, egg, or peanut (n = 20-27 for each food). Change in sIgE level and SPT wheal size was measured after 446 and 453 accidental exposure reactions, respectively. The median change in sIgE level was a decrease of 0.33 kU(A)/L (P < .01) after milk and 0.34 kU(A)/L (P < .01) after egg reactions, but no other statistically significant changes in sIgE level or SPT wheal size were observed for milk, egg, or peanut. When we limited the analysis to only those participants who had diagnostic testing done within 6 months of an accidental exposure reaction, we found that peanut SPT wheal size increased by 1.75 mm (P < .01), but a significant increase was not noted when all participants with testing done within 12 months were considered. The results suggest that reactions from OFCs and accidental exposure are not associated with increases in sensitization among children allergic to milk, egg, or peanut. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Exhaled nitric oxide levels in school children in relation to IgE sensitisation and window pane condensation.

PubMed

Janson, Christer; Kalm-Stephens, Pia; Foucard, Tony; Norbäck, Dan; Alving, Kjell; Nordvall, S Lennart

2005-08-01

A positive relation between exhaled nitric oxide (NO) levels and allergen exposure has been found in some studies whereas there is less information on how non-allergen environmental factors influences exhaled NO. To study the relationship between exhaled NO levels in schoolchildren in relation to IgE sensitisation and allergenic and non-allergenic environmental factors. This study comprised 374 schoolchildren (13-14 years of age) who performed exhaled NO-measurements and skin prick tests. Exposure to allergens, respiratory infections, environmental tobacco smoke and home window pane condensation, the latter an indicator of high humidity and poor ventilation was evaluated through questionnaires. In IgE-sensitised children sensitisation to pets was a more important determinant of exhaled NO than sensitisation to pollen. Higher NO levels were found in cat-sensitised children with a cat or other furred pets at home compared to cat-sensitised children without pets (geometric mean, 24.0 vs. 13.9 ppb, P=0.03). Significantly higher exhaled NO levels were found in non-sensitised children that reported having a cold (5.7 vs. 3.8 ppb, P<0.001) or lived in homes with window pane condensation (7.1 vs. 4.4 ppb, P=0.01) than in non-sensitised children without a cold and window pane condensation, respectively. These associations were not found in children that were sensitised to inhalation allergens. Allergen exposure seems to be the most important determinant for exhaled NO levels in IgE-sensitised children whereas in non-sensitised children NO levels were associated with respiratory infections and home window pane condensation.

Predicting food challenge outcomes for baked milk: role of specific IgE and skin prick testing.

PubMed

Bartnikas, Lisa M; Sheehan, William J; Hoffman, Elaine B; Permaul, Perdita; Dioun, Anahita F; Friedlander, James; Baxi, Sachin N; Schneider, Lynda C; Phipatanakul, Wanda

2012-11-01

Cow's milk allergy is the most common food allergy in childhood. Many children with IgE-mediated cow's milk allergy may tolerate baked milk products, but few data exist on predictors of outcomes of baked milk challenges. To determine the relation of milk protein allergen specific IgE (sIgE) levels and skin prick test (SPT) wheal size with baked milk challenge outcomes. A retrospective medical record review was conducted of 35 baked milk challenges. SPT results, sIgE levels, demographic characteristics, and food challenge results were analyzed. Thirty-five children underwent open challenges to baked milk and 29 (83%) passed. Of those who failed, 3 (50%) passed the initial clinic challenge but developed symptoms to ongoing exposure at home, days to months later. One child who ultimately failed at home required epinephrine. Compared with those who passed, children who failed were younger (median age, 8.9 and 3.7 years, respectively; P = .02). Children with a milk SPT wheal less than 12 mm were more than 90% likely to pass a baked milk challenge, and no child with a milk SPT wheal less than 7 mm failed a baked milk challenge. We were also able to establish more than 90% predictive values for passing baked milk challenges with a casein SPT wheal of 9 mm, a milk sIgE level of 1.0 kU/L, and a casein sIgE level of 0.9 kU/L. Most children allergic to cow's milk tolerated baked milk. Milk protein SPT wheal may be more reliable than sIgE level in predicting outcomes of baked milk challenges. It is important to be aware of the possibility of late reactions to ongoing baked milk exposure. Copyright © 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Positive Skin Test or Specific IgE to Penicillin Does Not Reliably Predict Penicillin Allergy.

PubMed

Tannert, Line Kring; Mortz, Charlotte Gotthard; Skov, Per Stahl; Bindslev-Jensen, Carsten

According to guidelines, patients are diagnosed with penicillin allergy if skin test (ST) result or specific IgE (s-IgE) to penicillin is positive. However, the true sensitivity and specificity of these tests are presently not known. To investigate the clinical relevance of a positive ST result and positive s-IgE and to study the reproducibility of ST and s-IgE. A sample of convenience of 25 patients with positive penicillin ST results, antipenicillin s-IgE results, or both was challenged with their culprit penicillin. Further 19 patients were not challenged, but deemed allergic on the basis of a recent anaphylactic reaction or delayed reactions to skin testing. Another sample of convenience of 18 patients, 17 overlapping with the 25 challenged, with initial skin testing and s-IgE (median, 25; range, 3-121), months earlier (T -1 ), was repeat skin tested and had s-IgE measured (T 0 ), and then skin tested and had s-IgE measured 4 weeks later (T 1 ). Only 9 (36%) of 25 were challenge positive. There was an increased probability of being penicillin allergic if both ST result and s-IgE were positive at T 0 . Positive ST result or positive s-IgE alone did not predict penicillin allergy. Among the 18 patients repeatedly tested, 46.2% (12 of 25) of positive ST results at T -1 were reproducibly positive at T 0 . For s-IgE, 54.2% (14 of 24) positive measurements were still positive at T 0 and 7 converted to positive at T 1 . The best predictor for a clinically significant (IgE-mediated) penicillin allergy is a combination of a positive case history with simultaneous positive ST result and s-IgE or a positive challenge result. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

The Association between Tobacco Smoke and Serum Immunoglobulin E Levels in Korean Adults.

PubMed

Kim, Young Soo; Kim, Hee Yeon; Ahn, Hyo-Suk; Sohn, Tae Seo; Song, Jae Yen; Lee, Young Bok; Lee, Dong-Hee; Lee, Jae-Im; Jeong, Seong Cheol; Chae, Hiun Suk; Han, Kyungdo; Yeo, Chang Dong

2017-10-01

Objective Smoking is common in patients with allergic diseases. The aim of this study was to evaluate the cross-sectional association between the current smoking status and total and specific Immunoglobulin E (IgE) levels in Korean adults. Methods Data were obtained from the 2010 Korean National Health and Nutrition Examination Survey, a national cross-sectional study. We analyzed the data of subjects whose smoking status and serum IgE levels were of acceptable quality. Results A total of 1,963 subjects (1,118 never smokers, 340 ex-smokers, and 505 current smokers) were included. The total IgE levels and specific IgE levels to house dust mite Dermatophagoides farinae (Df), cockroach, and dog allergens in never smokers were significantly (p<0.0001) lower than in ex-smokers or current smokers. After adjusting for other variables, current smokers independently had significantly higher levels of total IgE and cockroach-specific IgE than ex-smokers or never smokers. The proportions of subjects with total IgE ≥150 kU/L and specific IgE ≥0.35 kU/L to Df-specific IgE were significantly (p value for trend <0.05) increased in ex-smokers and current smokers. The total IgE levels and IgE levels specific to Df, cockroaches, and dogs significantly (p value for trend <0.05) and proportionally increased with increasing numbers of cigarettes smoked daily. Conclusion Smoking was associated with elevated total IgE levels and IgE levels specific to Df, cockroach, and dog allergens in a cumulative, dose-dependent manner. Furthermore, current smoking status was an independent risk factor for elevated total IgE levels and IgE levels specific to cockroach allergen.

The relationship between cord blood immunoglobulin E levels and allergy-related outcomes in young adults.

PubMed

Shah, Purvee S; Wegienka, Ganesa; Havstad, Suzanne; Johnson, Christine Cole; Ownby, Dennis R; Zoratti, Edward M

2011-03-01

Elevated cord blood IgE may be associated with a higher risk of allergic disease. To determine whether cord blood IgE is associated with allergic biomarkers or allergic disorders in young adults. Data was collected from 670 subjects 18-21 years of age that were among 835 original participants in the Detroit Childhood Allergy Study, a general risk, population-based birth cohort. Cord blood IgE was assessed in relation to biomarkers associated with allergy and asthma including total IgE, allergen-specific IgE, blood eosinophilia, and spirometry. Cord blood IgE was also analyzed for associations to subsequent allergic disease including atopic dermatitis, allergic rhinitis, and asthma. Cord blood IgE, analyzed as a continuous measure, was modestly correlated with total IgE (r = 0.18, P < .001) and higher cord IgE was associated with a higher likelihood of sensitization to common allergens in young adults (OR = 1.18, 95% CI, 1.02-1.37; P = .031). The relationship between cord IgE and sensitization was stronger among teens with no pet exposure in the first year of life (OR = 1.43, 95% CI, 1.16-1.77; P = .001). No relationship was found between cord IgE and blood eosinophil counts or lung function. In addition, no consistent association of cord blood IgE to asthma, allergic rhinitis, or atopic dermatitis was apparent. An elevated cord blood IgE level modestly correlates with elevated total IgE and is associated with a slightly higher likelihood of allergic sensitization among young adults. However, cord IgE is not a strong predictor of clinical allergic disorders in this age group. Copyright © 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

SLP-76 is required for high-affinity IgE receptor- and IL-3 receptor-mediated activation of basophils.

PubMed

Hidano, Shinya; Kitamura, Daisuke; Kumar, Lalit; Geha, Raif S; Goitsuka, Ryo

2012-11-01

Basophils have been reported to play a critical role in allergic inflammation by secreting IL-4 in response to IL-3 or high-affinity IgE receptor (FcεRI)-cross-linking. However, the signaling pathways downstream of FcεRI and the IL-3 receptor in basophils have yet to be determined. In the present study, we used mice deficient in SLP-76 (Src homology 2 domain-containing leukocyte phosphoprotein of 76kDa) to demonstrate critical functions of this adaptor molecule in transducing FcεRI- and IL-3 receptor-mediated signals that induce basophil activation. Although SLP-76 was dispensable for in vivo differentiation, as well as IL-3-induced in vitro proliferation of basophils, IL-4 production induced by both stimuli was completely ablated by SLP-76 deficiency. Biochemical analyses revealed that IL-3-induced phosphorylation of phospholipase C (PLC) γ2 and Akt, but not STAT5, was severely reduced in SLP-76-deficient basophils, whereas FcεRI cross-linking phosphorylation of PLCγ2, but not Akt, was abrogated by SLP-76 deficiency, suggesting important differences in the requirement of SLP-76 for Akt activation between FcεRI- and IL-3 receptor-mediated signaling pathways in basophils. Because IL-3-induced IL-4 production was sensitive to calcineurin inhibitors and an intracellular calcium chelator, in addition to PI3K inhibitors, SLP-76 appears to regulate FcεRI- and IL-3 receptor-induced IL-4 production via mediating PLCγ2 activation in basophils. Taken together, these findings indicate that SLP-76 is an essential signaling component for basophil activation downstream of both FcεRI and the IL-3 receptor.

Peanut sensitization pattern in Norwegian children and adults with specific IgE to peanut show age related differences.

PubMed

Namork, Ellen; Stensby, Berit A

2015-01-01

Peanuts contain potent food allergens and the prevalence of allergy is reported to increase, especially in children. Since peanut sensitization may differ between different geographical regions, we wanted to investigate the sensitization pattern to the individual peanut allergens in a Norwegian population. Cases reported to the Norwegian Food Allergy Register with sera positive to peanut extract were analyzed for specific IgE (sIgE) to the recombinant peanut allergens Ara h 1, Ara h 2, Ara h 3, Ara h 8 and Ara h 9 and to birch pollen extract. Serum samples negative to the above allergens were analyzed for sIgE to Ara h 6, and sIgE to Pru p 3 in peach were analyzed in sera positive to the cross-reactive allergen Ara h 9. Highest frequency of sIgE to Ara h 2, often co-sensitized to Ara h 1 and 3, were found in the small children up to 6 years of age. From the age of 6 years, sensitization to Ara h 8 was predominant. The sIgE levels to the storage proteins Ara h 1, 2 and 3 were strongly correlated, as was the sIgE levels to Ara h 8 and birch pollen extract. A low sensitization rate of sIgE to Ara h 9 in young adults was observed, which sIgE levels were very strongly correlated to Pru p 3. The sensitization to peanut allergens in a Norwegian population shows a clear age dependent pattern. The results add to the previously published research on the sensitization patterns of peanut sensitized patients in different geographical areas.

Differences in the Importance of Mast Cells, Basophils, IgE, and IgG versus That of CD4+ T Cells and ILC2 Cells in Primary and Secondary Immunity to Strongyloides venezuelensis.

PubMed

Mukai, Kaori; Karasuyama, Hajime; Kabashima, Kenji; Kubo, Masato; Galli, Stephen J

2017-05-01

There is evidence that mast cells, basophils, and IgE can contribute to immune responses to parasites; however, the relative levels of importance of these effector elements in parasite immunity are not fully understood. Previous work in Il3 -deficient and c- kit mutant Kit W / W-v mice indicated that interleukin-3 and c-Kit contribute to expulsion of the intestinal nematode Strongyloides venezuelensis during primary infection. Our findings in mast cell-deficient Kit W-sh / W-sh mice and two types of mast cell-deficient mice that have normal c- kit ("Hello Kit ty" and MasTRECK mice) confirmed prior work in Kit W / W-v mice that suggested that mast cells play an important role in S. venezuelensis egg clearance in primary infections. We also assessed a possible contribution of basophils in immune responses to S. venezuelensis By immunohistochemistry, we found that numbers of basophils and mast cells were markedly increased in the jejunal mucosa during primary infections with S. venezuelensis Studies in basophil-deficient Mcpt8 DTR mice revealed a small but significant contribution of basophils to S. venezuelensis egg clearance in primary infections. Studies in mice deficient in various components of immune responses showed that CD4 + T cells and ILC2 cells, IgG, FcRγ, and, to a lesser extent, IgE and FcεRI contribute to effective immunity in primary S. venezuelensis infections. These findings support the conclusion that the hierarchy of importance of immune effector mechanisms in primary S. venezuelensis infection is as follows: CD4 + T cells/ILC2 cells, IgG, and FcRγ>mast cells>IgE and FcεRI>basophils. In contrast, in secondary S. venezuelensis infection, our evidence indicates that the presence of CD4 + T cells is of critical importance but mast cells, antibodies, and basophils have few or no nonredundant roles. Copyright © 2017 American Society for Microbiology.

Biomarkers for non-human primate type-I hypersensitivity: antigen-specific immunoglobulin E assays.

PubMed

Clark, Darcey; Shiota, Faith; Forte, Carla; Narayanan, Padma; Mytych, Daniel T; Hock, M Benjamin

2013-06-28

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 10 ng/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. Copyright © 2013 Elsevier B.V. All rights reserved.

A study of IgE sensitization and skin response to histamine in Asian-Pacific American adults.

PubMed

Lee-Wong, Mary; Chou, Vivian; Silverberg, Jonathan I

2012-01-01

Allergic disorders and skin response to histamine have been noted to vary in different ethnicities. We investigated IgE-mediated allergic sensitization and skin response to histamine in Asian Pacific Americans (APAs), black and Hispanic Americans, and white adults. A retrospective questionnaire-based study was performed of 2222 adults presenting at a New York City allergy referral center from 1994 to 2003. Questionnaire data included sex, age, and ethnicity and personal and family history of atopic disorders. Skin-prick test (SPT) data included saline and histamine controls and response to a standardized panel of 10 aeroallergens. APA patients had a lower odds of asthma (adjusted odds ratio [aOR], 0.68; 95% confidence interval [CI], 0.52-0.89; p = 0.005) and/or animal allergies (aOR, 0.64; 95% CI, 0.50-0.82; p = 0.0003). Histamine response was not significantly different in APA (aOR, 0.90; 95% CI, 0.73-1.12; p = 0.36) or Hispanic Americans (aOR, 1.03; 95% CI, 0.85-1.24; p = 0.76), but was higher in black Americans (aOR, 2.32; 95% CI, 1.67-3.21; p < 0.0001). APA had higher odds of a positive SPT to trees (aOR, 1.49; 95% CI, 1.16-1.91; p = 0.002), grasses (aOR, 1.32; 95% CI, 1.05-1.43; p = 0.02), feathers (aOR, 1.65; 95% CI, 1.31-2.09; p < 0.0001), and cockroaches (aOR, 1.37; 95% CI, 1.10-1.62; p = 0.005). Moreover, APA had a higher total number of positive SPTs when compared with white patients (5.5 ± 3.2 versus 4.9 ± 3.3; aOR, 1.34; 95% CI, 1.10-1.62 p = 0.004). APA adults in our patient population had more IgE sensitizations but not an increased skin response to histamine. In contrast, black Americans had increased skin response to histamine.

Allergy Blood Test

MedlinePlus

... have an allergy. Other names: IgE allergy test, Quantitative IgE, Immunoglobulin E, Total IgE, Specific IgE What ... Thermo Fisher Scientific Inc.; c2017. ImmunoCAP – a truly quantitative allergy test [cited 2017 Feb 24]; [about 3 ...

Sensitization to minor cat allergen components is associated with type-2 biomarkers in young asthmatics.

PubMed

Tsolakis, N; Malinovschi, A; Nordvall, L; Mattsson, L; Lidholm, J; Pedroletti, C; Janson, C; Borres, M P; Alving, K

2018-03-25

Cat allergy is a major trigger of asthma world-wide. Molecular patterns of cat sensitization vary between individuals, but their relationship to inflammation in asthmatics has not been extensively studied. To investigate the prevalence and levels of IgE antibodies against different cat allergen components and their relationship to type-2 inflammation and total IgE among young asthmatic subjects sensitized to furry animals. Patients with asthma (age 10-35 years; n = 266) and IgE sensitization to cat, dog or horse extract (ImmunoCAP), were analysed for IgE to the cat allergen components Fel d 1 (secretoglobin), Fel d 2 (serum albumin), Fel d 4 and Fel d 7 (lipocalins). Independent associations between IgE-antibody concentrations, and fraction of exhaled nitric oxide (FeNO), blood eosinophil (B-Eos) count, and total IgE were analysed by multiple linear regression after adjustment for possible confounders. The level of IgE against Fel d 2 was independently related to FeNO (P = .012) and total IgE (P < .001), and IgE against Fel d 4 associated with Β-Eos count (P = .009) and total IgE (P < .001). IgE antibodies against Fel d 1 or cat extract did not independently relate to these inflammatory markers (P = .23-.51). Levels of IgE to lipocalin (Fel d 4) and serum albumin (Fel d 2), but not to secretoglobin (Fel d 1) or cat extract, were independently associated with type-2 biomarkers and total IgE in young asthmatics. We suggest that measurement of IgE to minor cat allergen components may be useful when investigating asthma morbidity in cat allergic subjects. © 2018 John Wiley & Sons Ltd.

Risk factors for sensitisation to methyltetrahydrophthalic anhydride.

PubMed

Yokota, K; Johyama, Y; Yamaguchi, K; Fujiki, Y; Takeshita, T; Morimoto, K

1997-09-01

To examine an association between specific IgE to methyltetrahydrophthalic anhydride (MTHPA) and exposure time, atopic history, smoking habits, and total IgE concentrations. A cross sectional survey was carried out on a population of 148 workers from two condenser plants using epoxy resin with MTHPA, an acid anhydride curing agent known to cause allergy. Using a Pharmacia CAP system with a MTHPA human serum albumin conjugate, specific IgE antibody was detected in serum from 97 (66%) out of the 148 workers exposed to MTHPA. Stepwise multiple linear regression analysis showed a striking relation between log concentrations of specific and total IgE (P < 0.0001). Furthermore, when the workers were divided into two groups according to a cut-off point (100 IU/ml) between low and high total IgE, current smoking was significantly (P = 0.025) associated with specific IgE production only in the group with low total IgE (< 100 IU/ml). Smoking is the most significant risk factor for raising specific IgE to MTHPA in the group with low total IgE concentrations.

Occupational asthma, eosinophil and skin prick tests and serum total IgE values of the workers in a plant manufacturing rose oil.

PubMed

Akkaya, A; Ornek, Z; Kaleli, S

2004-01-01

This study was aimed to determine the rate of occupational asthma (OA) in workers at a rose extracting plant. Specific clinical tests of 52 workers, randomly chosen from four local rose extracting plants, were statistically compared with the test results of 30 local control subjects of similar age and sex as the plant workers, but who had never worked in such a plant. There were no significant differences in pulmonary function tests (FVC, FEV1, FEV1/FVC, PEFR) between the control and test groups. Significantly higher serum total IgE values (p < 0.0001) were observed for the test subjects (239.08+/-240 IU/ml) compared to the control subjects (81.33+/-61.45 IU/ml). There were also significant differences (p < 0.0001) in the number of eosinophils between the control and test groups, with corresponding mean values of 2.28+/-2.75% and 0.73+/-1.72%, respectively. A specifically prepared skin prick test using a rose allergen (Rosa domescena) was positive for 53.84% in the test subjects whereas only 5.33% positive test results were seen in the control group. We have demonstrated the involvement of Rosa domescena pollen in occupational allergy, through IgE-mediated hypersensitivity. It was concluded that the workers of a rose oil extracting plant are more susceptible to the rose pollens.

The effect of oral immunotherapy treatment in severe IgE mediated milk, peanut, and egg allergy in adults.

PubMed

Mäntylä, Jarkko; Thomander, Tuuli; Hakulinen, Auli; Kukkonen, Kaarina; Palosuo, Kati; Voutilainen, Helena; Pelkonen, Anna; Kauppi, Paula

2018-06-01

The standard care of severe food allergy in both adults and children means avoidance of allergens. In recent years promising results of oral immunotherapy (OIT) have been reported in children. In adults, information on OIT in severe food allergy is very limited. We aimed to study if OIT is possible in adults. We report OIT results in 10 adult patients with milk OIT, nine adult patients with peanut OIT, and four adult patients with egg OIT. The allergy was confirmed with allergen specific IgE tests and oral food challenges (open in milk allergy and double-blind in peanut and egg allergy). The OIT was performed as open. The median dose of protein that led to discontinuation of allergen challenge because of symptoms was 7.5 mg in milk allergy, 25 mg in peanut allergy, and 15 mg in egg allergy. The median period of OIT was 515 days. Currently on OIT are 6/10 milk allergic patients, 4/9 peanut allergic patients and 3/4 egg allergic patients. The median dose of milk protein increased by 60-fold during OIT compared to the allergen challenge dose. In peanut OIT the median dose increased by eightfold and in egg allergy the dose increased with OIT by 35-fold. Local itching was the most common side effect of OIT (73.9% of the patients), four patients reported having used epinephrine autoinjector and three patients having needed emergency room treatment. OIT can be given in adult patients with severe milk, peanut, or egg allergy only in selected cases. OIT leads into desensitization but it is not clear whether persistent tolerance can be achieved. Mild adverse events during OIT are common. © 2018 The Authors. Immunity, Inflammation and Disease Published by John Wiley & Sons Ltd.

Skin prick testing and peanut-specific IgE can predict peanut challenge outcomes in preschoolchildren with peanut sensitization.

PubMed

Johannsen, H; Nolan, R; Pascoe, E M; Cuthbert, P; Noble, V; Corderoy, T; Franzmann, A; Loh, R; Prescott, S L

2011-07-01

The rise in peanut allergy is a source of considerable burden in the community. A growing number of preschoolchildren have been identified as peanut sensitized in the course of investigation of other allergic conditions. Although many have never knowingly ingested peanuts and their clinical reactivity is not known, it has been common practice to place these children on avoidance diets for many years. To determine the utility of skin prick tests (SPT) and fluorescent-enzyme immunoassays (FEIA) for identifying either peanut allergy or tolerance in preschoolchildren with peanut sensitization. Forty-nine preschoolchildren (<5 years of age) with peanut sensitization (SPT ≥ 2 mm or peanut-specific IgE ≥ 0.35 kU/L) but unknown clinical reactivity had graded open peanut challenges reaching a total of 11 g. A positive challenge was defined as an objective IgE-mediated reaction during challenge or the 2-h observation. Forty-nine percent (24/49) of children had positive challenges. An SPT of >7 mm on the day of challenge predicted a positive challenge with a sensitivity of 83% and a negative predictive value (NPV) of 84%. An FEIA of >2.0 kU/L showed a sensitivity of 79% and an NPV of 80%. Predicting challenge outcome from a combination of SPT and FEIA (SPT >7 and/or FEIA >2 is positive) increased sensitivity to 96% and NPV to 95%. At least half of preschoolchildren with peanut sensitization and no antecedent history of peanut ingestion can tolerate peanuts. A SPT<7 mm and FEIA<2 kU/L identify children most likely to tolerate peanut, with only a 5% likelihood of failing an oral challenge. This study assists clinicians considering challenges in very young peanut-sensitized children. © 2011 Blackwell Publishing Ltd.

African Ancestry is a Risk Factor for Asthma and High Total IgE Levels in African Admixed Populations

PubMed Central

Vergara, Candelaria; Murray, Tanda; Rafaels, Nicholas; Lewis, Rachel; Campbell, Monica; Foster, Cassandra; Gao, Li; Faruque, Mezbah; Oliveira, Ricardo Riccio; Carvalho, Edgar; Araujo, Maria Ilma; Cruz, Alvaro A.; Watson, Harold; Mercado, Dilia; Knight-Madden, Jennifer; Ruczinski, Ingo; Dunston, Georgia; Ford, Jean; Caraballo, Luis; Beaty, Terri H.; Mathias, Rasika A.; Barnes, Kathleen C.

2014-01-01

Characterization of genetic admixture of populations in the Americas and the Caribbean is of interest for anthropological, epidemiological, and historical reasons. Asthma has a higher prevalence and is more severe in populations with a high African component. Association of African ancestry with asthma has been demonstrated. We estimated admixture proportions of samples from six trihybrid populations of African descent and determined the relationship between African ancestry and asthma and total serum IgE levels (tIgE). We genotyped 237 ancestry informative markers in asthmatics and nonasthmatic controls from Barbados (190/277), Jamaica (177/529), Brazil (40/220), Colombia (508/625), African Americans from New York (207/171), and African Americans from Baltimore/Washington, D.C. (625/757). We estimated individual ancestries and evaluated genetic stratification using Structure and principal component analysis. Association of African ancestry and asthma and tIgE was evaluated by regression analysis. Mean SD African ancestry ranged from 0.76 ± 0.10 among Barbadians to 0.33 ± 0.13 in Colombians. The European component varied from 0.14 ± 0.05 among Jamaicans and Barbadians to 0.26 ± 0.08 among Colombians. African ancestry was associated with risk for asthma in Colombians (odds ratio (OR) = 4.5, P = 0.001) Brazilians (OR = 136.5, P = 0.003), and African Americans of New York (OR: 4.7; P = 0.040). African ancestry was also associated with higher tIgE levels among Colombians (β = 1.3, P = 0.04), Barbadians (β = 3.8, P = 0.03), and Brazilians (β = 1.6, P = 0.03). Our findings indicate that African ancestry can account for, at least in part, the association between asthma and its associated trait, tIgE levels. PMID:23554133

Lipopolysaccharide-reactive immunoglobulin E is associated with lower mortality and organ failure in traumatically injured patients.

PubMed Central

DiPiro, J T; Hamilton, R G; Howdieshell, T R; Adkinson, N F; Mansberger, A R

1994-01-01

Antilipopolysaccharide (anti-LPS) immunoglobulin G (IgG) and IgM have been associated with protection from LPS effects in vivo. We investigated the presence of IgE and anti-LPS in 32 patients that had experienced severe traumatic injury and in 35 healthy volunteers; we also investigated whether IgE anti-LPS was associated with important clinical events. Plasma samples were collected daily from patients in the intensive care unit and on one occasion from volunteers; the samples were assayed for IgE anti-LPS. IgE anti-LPS was assayed by enzyme-linked immunosorbent assay with monoclonal anti-human IgE as the capture antibody. Detection was accomplished with biotin-labeled LPS (Escherichia coli J5 mutant) followed by streptavidin-peroxidase with 2,2'-azino(3-ethylbenzthiazoline)sulfonic acid as the substrate. The assay was demonstrated to be specific for IgE and LPS-biotin by nonreactivity of control sera with high-titer anti-LPS IgG and IgM and by inhibition with unlabeled LPS. IgE anti-LPS was detected in 1 of 35 healthy controls (2.9%) and 25 of 32 traumatically injured patients (78%) (P < 0.001). The presence of IgE anti-LPS was associated with a lower incidence of death (P = 0.026) and of renal failure (P = 0.0012). There was no apparent temporal relationship between detection of IgE anti-LPS and clinical events. IgG anti-LPS was detected more frequently in patients that were positive for IgE anti-LPS (P = 0.06) but was not associated with clinical events. The inability to detect IgE anti-LPS may be related to adverse clinical events through depletion of specific IgE due to LPS exposure after trauma or through saturation of the assay by IgE with other specificities. We have reported increased total IgE concentrations in these patients. (J.T. DiPiro, R.G. Hamilton, T. R. Howdieshell, N. F. Adkinson, and A. R. Mansberger, Ann. Surg. 215:460-466, 1992). PMID:7496965

Evidence-based guidelines for anti-allergic drug withdrawal times before allergen-specific intradermal and IgE serological tests in dogs.

PubMed

Olivry, Thierry; Saridomichelakis, Manolis

2013-04-01

Anti-allergic drugs (e.g. antihistamines, glucocorticoids and ciclosporin) are often administered to dogs with atopic dermatitis to relieve pruritus and skin lesions. Allergen-specific intradermal tests (IDT) and allergen-specific IgE serological (ASIS) tests are used to characterize the allergens to which dogs are hypersensitive. Anti-allergic drugs have the potential to influence the results or interpretation of these tests. To provide evidence-based recommendations for anti-allergic drug withdrawal times before IDT and ASIS tests. Three citation databases and abstracts from international meetings were searched for relevant studies. Studies were grouped based on similar interventions and types of tests. Withdrawal times for each type of drug and test were then extrapolated from the study results. Before the assessment of immediate reactions to IDT, proposed optimal withdrawal times for antihistamines, oral glucocorticoids, topical/otic glucocorticoids and ciclosporin are 7, 14, 14 and 0 days, respectively. Studies have provided no evidence for drug withdrawal prior to ASIS tests for oral ciclosporin or prednisone/prednisolone. Owing to a lack of studies, recommendations for withdrawal times before ASIS tests cannot be made for topical glucocorticoids and antihistamines. These proposed withdrawal times are based on the existing evidence at the end of 2011. Care must be taken before extrapolating the suggested withdrawal times to other species, higher dosages, different formulations and/or durations of administration of tested drugs, as well as to other medications from the same category. © 2013 The Authors. Veterinary Dermatology © 2013 ESVD and ACVD.

The Natural History of IgE-Mediated Food Allergy: Can Skin Prick Tests and Serum-Specific IgE Predict the Resolution of Food Allergy?

PubMed Central

Peters, Rachel L.; Gurrin, Lyle C.; Dharmage, Shyamali C.; Koplin, Jennifer J.; Allen, Katrina J.

2013-01-01

IgE-mediated food allergy is a transient condition for some children, however there are few indices to predict when and in whom food allergy will resolve. Skin prick test (SPT) and serum-specific IgE levels (sIgE) are usually monitored in the management of food allergy and are used to predict the development of tolerance or persistence of food allergy. The aim of this article is to review the published literature that investigated the predictive value of SPT and sIgE in development of tolerance in children with a previous diagnosis of peanut, egg and milk allergy. A systematic search identified twenty-six studies, of which most reported SPT or sIgE thresholds which predicted persistent or resolved allergy. However, results were inconsistent between studies. Previous research was hampered by several limitations including the absence of gold standard test to diagnose food allergy or tolerance, biased samples in retrospective audits and lack of systematic protocols for triggering re-challenges. There is a need for population-based, prospective studies that use the gold standard oral food challenge (OFC) to diagnose food allergy at baseline and follow-up to develop SPT and sIgE thresholds that predict the course of food allergy. PMID:24132133

Total serum immunoglobulin E level and specific allergens in adults with skin diseases.

PubMed

Choi, Byung Gon; Lee, Yang Won; Choe, Yong Beom; Ahn, Kyu Joong

2018-01-01

Immunoglobulin E (IgE) plays an important role in allergic diseases. Although several studies have shown the association of serum total IgE and allergen-specific IgE levels with allergic dermatological diseases such as atopic dermatitis, there are few studies addressing this association for skin diseases in general. We sought to evaluate IgE levels in skin diseases and investigate the differences based on the disease type and clinical factors such as gender and age. Data from 2836 patients who visited the dermatologic clinic of the Konkuk University Hospital, Seoul, Republic of Korea for 4 years were reviewed to document IgE levels and clinical information. IgE levels were collated with the type of skin disease, gender, and age. Patients with atopic dermatitis had a much higher total IgE level and were more susceptible to allergens as compared to other disease groups. Patients in other disease groups showed no significant differences in IgE levels. Men showed higher total IgE levels but the gender differences decreased with increasing age. The data were collected from patients at a referral centre and thus may not represent the general population of dermatologic patients. There was a lack of information regarding factors that could potentially influence IgE levels such as smoking history and disease severity. The results suggest that there are physiological or environmental differences in IgE-mediated immune responses between males and females. Also, except for atopic dermatitis, there were no clinical differences in the IgE levels among various skin diseases.

Garlic and onion sensitization among Saudi patients screened for food allergy: a hospital based study.

PubMed

Almogren, A; Shakoor, Z; Adam, M H

2013-09-01

Detection of specific IgE antibodies against food materials indicates allergic sensitization. Some very widely consumed foods materials such as garlic and onion have rarely been investigated for their allergenic potential. To assess the presence of garlic and onion specific IgE antibodies in patients investigated for food allergy. Radioallergosorbent test (RAST) results of 108 patients with clinical suspicion of food allergy who were specifically screened for garlic and onion specific IgE antibodies along with other food allergens were analyzed retrospectively at King Khalid University Hospital between January 2008 and April 2009. This group of patients included 73 males and 35 females with mean age 27+13.2 years. Estimation of garlic and onion specific IgE antibodies was performed by radioallergosorbent test (RAST) using Pharmacia ImmunoCAP 250 analyzer. Out of the 108 patients 15 (13.8%) had garlic and onion specific IgE antibodies in their sera. Garlic specific IgE antibodies with the RAST scores between one to four were present in 14 and onion specific IgE were detected in 13 patients. For garlic specific IgEs majority of patients (08) had RAST score of one (0.35-0.69 kU/L) and for onion specific IgE antibodies seven patients had RAST score of two (0.70-3.49 kU/L). Among these patients 12 (80%) were found to have coexisting specific IgE antibodies against garlic and onion. The presence of garlic and onion specific IgE antibodies in a sizeable number of patients indicate sensitization and allergenic potential of these food materials.

Pearls and pitfalls of allergy diagnostic testing: report from the American College of Allergy, Asthma and Immunology/American Academy of Allergy, Asthma and Immunology Specific IgE Test Task Force.

PubMed

Cox, Linda; Williams, Brock; Sicherer, Scott; Oppenheimer, John; Sher, Larry; Hamilton, Robert; Golden, David

2008-12-01

The intended purpose of this monograph is to provide a general overview of allergy diagnostics for health care professionals who care for patients with allergic disease. For a more comprehensive review of allergy diagnostic testing, readers can refer to the Allergy Diagnostic Practice Parameters. A key message is that a positive allergy test result (skin or blood) indicates only the presence of allergen specific IgE (called sensitization). It does not necessarily mean clinical allergy (ie, allergic symptoms with exposure). It is important for this reason that the allergy evaluation be based on the patient's history and directed by a health care professional with sufficient understanding of allergy diagnostic testing to use the information obtained from his/her evaluation of the patient to determine (1) what allergy diagnostic tests to order, (2) how to interpret the allergy diagnostic test results, and (3) how to use the information obtained from the allergy evaluation to develop an appropriate therapeutic treatment plan.

Detection of cross-reactivity for atopic immunoglobulin E against multiple allergens.

PubMed

Chiou, Yee-Hsuan; Yuo, Chung-Yee; Wang, Lin-Yu; Huang, Shiao-ping

2003-03-01

The existence of specific immunoglobulin E (IgE) allows us to determine the allergens that cause the allergic disease. For the purposes of allergen avoidance and immunotherapy, the measurement of specific IgE is widely applied in clinical laboratories. However, if IgE from the serum of an allergic patient exhibits reactivity to multiple allergens, it would cause a problem. The present study analyzes whether the serum IgE with multiple reactivity is due to the presence of unique IgE against the common epitope shared by different allergens or the presence of multiple IgEs against different epitopes on different allergens. The quantitative-competitive inhibition tests and the immunoblotting were applied to analyze the immunosimilarity among examined allergens. The result shows that the competitive inhibition of IgE binding between shrimp and crab allergens is higher than those between either shrimp and cockroach or between crab and cockroach. Furthermore, the results of immunoblotting are consistent with those of quantitative-competitive inhibition tests. These results allow us to detect the cross-reactivity for atopic IgE against multiple allergens.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pennington, Luke F.; Tarchevskaya, Svetlana; Brigger, Daniel

Omalizumab is a widely used therapeutic anti-IgE antibody. Here we report the crystal structure of the omalizumab–Fab in complex with an IgE-Fc fragment. This structure reveals the mechanism of omalizumab-mediated inhibition of IgE interactions with both high- and low-affinity IgE receptors, and explains why omalizumab selectively binds free IgE. The structure of the complex also provides mechanistic insight into a class of disruptive IgE inhibitors that accelerate the dissociation of the high-affinity IgE receptor from IgE. We use this structural data to generate a mutant IgE-Fc fragment that is resistant to omalizumab binding. Treatment with this omalizumab-resistant IgE-Fc fragment, inmore » combination with omalizumab, promotes the exchange of cell-bound full-length IgE with omalizumab-resistant IgE-Fc fragments on human basophils. Furthermore, this combination treatment also blocks basophil activation more efficiently than either agent alone, providing a novel approach to probe regulatory mechanisms underlying IgE hypersensitivity with implications for therapeutic interventions.« less

Genetic composition of social groups influences male aggressive behaviour and fitness in natural genotypes of Drosophila melanogaster.

PubMed

Saltz, Julia B

2013-11-22

Indirect genetic effects (IGEs) describe how an individual's behaviour-which is influenced by his or her genotype-can affect the behaviours of interacting individuals. IGE research has focused on dyads. However, insights from social networks research, and other studies of group behaviour, suggest that dyadic interactions are affected by the behaviour of other individuals in the group. To extend IGE inferences to groups of three or more, IGEs must be considered from a group perspective. Here, I introduce the 'focal interaction' approach to study IGEs in groups. I illustrate the utility of this approach by studying aggression among natural genotypes of Drosophila melanogaster. I chose two natural genotypes as 'focal interactants': the behavioural interaction between them was the 'focal interaction'. One male from each focal interactant genotype was present in every group, and I varied the genotype of the third male-the 'treatment male'. Genetic variation in the treatment male's aggressive behaviour influenced the focal interaction, demonstrating that IGEs in groups are not a straightforward extension of IGEs measured in dyads. Further, the focal interaction influenced male mating success, illustrating the role of IGEs in behavioural evolution. These results represent the first manipulative evidence for IGEs at the group level.

Genetic composition of social groups influences male aggressive behaviour and fitness in natural genotypes of Drosophila melanogaster

PubMed Central

Saltz, Julia B.

2013-01-01

Indirect genetic effects (IGEs) describe how an individual's behaviour—which is influenced by his or her genotype—can affect the behaviours of interacting individuals. IGE research has focused on dyads. However, insights from social networks research, and other studies of group behaviour, suggest that dyadic interactions are affected by the behaviour of other individuals in the group. To extend IGE inferences to groups of three or more, IGEs must be considered from a group perspective. Here, I introduce the ‘focal interaction’ approach to study IGEs in groups. I illustrate the utility of this approach by studying aggression among natural genotypes of Drosophila melanogaster. I chose two natural genotypes as ‘focal interactants’: the behavioural interaction between them was the ‘focal interaction’. One male from each focal interactant genotype was present in every group, and I varied the genotype of the third male—the ‘treatment male’. Genetic variation in the treatment male's aggressive behaviour influenced the focal interaction, demonstrating that IGEs in groups are not a straightforward extension of IGEs measured in dyads. Further, the focal interaction influenced male mating success, illustrating the role of IGEs in behavioural evolution. These results represent the first manipulative evidence for IGEs at the group level. PMID:24068359

Patterns of postictal cerebral perfusion in idiopathic generalized epilepsy: a multi-delay multi-parametric arterial spin labelling perfusion MRI study.

PubMed

Chen, Guangxiang; Lei, Du; Ren, Jiechuan; Zuo, Panli; Suo, Xueling; Wang, Danny J J; Wang, Meiyun; Zhou, Dong; Gong, Qiyong

2016-07-04

The cerebral haemodynamic status of idiopathic generalized epilepsy (IGE) is a very complicated process. Little attention has been paid to cerebral blood flow (CBF) alterations in IGE detected by arterial spin labelling (ASL) perfusion magnetic resonance imaging (MRI). However, the selection of an optimal delay time is difficult for single-delay ASL. Multi-delay multi-parametric ASL perfusion MRI overcomes the limitations of single-delay ASL. We applied multi-delay multi-parametric ASL perfusion MRI to investigate the patterns of postictal cerebral perfusion in IGE patients with absence seizures. A total of 21 IGE patients with absence seizures and 24 healthy control subjects were enrolled. IGE patients exhibited prolonged arterial transit time (ATT) in the left superior temporal gyrus. The mean CBF of IGE patients was significantly increased in the left middle temporal gyrus, left parahippocampal gyrus and left fusiform gyrus. Prolonged ATT in the left superior temporal gyrus was negatively correlated with the age at onset in IGE patients. This study demonstrated that cortical dysfunction in the temporal lobe and fusiform gyrus may be related to epileptic activity in IGE patients with absence seizures. This information can play an important role in elucidating the pathophysiological mechanism of IGE from a cerebral haemodynamic perspective.

Birth order modifies the effect of IL13 gene polymorphisms on serum IgE at age 10 and skin prick test at ages 4, 10 and 18: a prospective birth cohort study

PubMed Central

2010-01-01

Background Susceptibility to atopy originates from effects of the environment on genes. Birth order has been identified as a risk factor for atopy and evidence for some candidate genes has been accumulated; however no study has yet assessed a birth order-gene interaction. Objective To investigate the interaction of IL13 polymorphisms with birth order on allergic sensitization at ages 4, 10 and 18 years. Methods Mother-infant dyads were recruited antenatally and followed prospectively to age 18 years. Questionnaire data (at birth, age 4, 10, 18); skin prick test (SPT) at ages 4, 10, 18; total serum IgE and specific inhalant screen at age 10; and genotyping for IL13 were collected. Three SNPs were selected from IL13: rs20541 (exon 4, nonsynonymous SNP), rs1800925 (promoter region) and rs2066960 (intron 1). Analysis included multivariable log-linear regression analyses using repeated measurements to estimate prevalence ratios (PRs). Results Of the 1456 participants, birth order information was available for 83.2% (1212/1456); SPT was performed on 67.4% at age 4, 71.2% at age 10 and 58.0% at age 18. The prevalence of atopy (sensitization to one or more food or aeroallergens) increased from 19.7% at age 4, to 26.7% at 10 and 41.1% at age 18. Repeated measurement analysis indicated interaction between rs20541 and birth order on SPT. The stratified analyses demonstrated that the effect of IL13 on SPT was restricted only to first-born children (p = 0.007; adjusted PR = 1.35; 95%CI = 1.09, 1.69). Similar findings were noted for firstborns regarding elevated total serum IgE at age 10 (p = 0.007; PR = 1.73; 1.16, 2.57) and specific inhalant screen (p = 0.034; PR = 1.48; 1.03, 2.13). Conclusions This is the first study to show an interaction between birth order and IL13 polymorphisms on allergic sensitization. Future functional genetic research need to determine whether or not birth order is related to altered expression and methylation of the IL13 gene. PMID:20403202

Inhibitory effect of carotenoids on the degranulation of mast cells via suppression of antigen-induced aggregation of high affinity IgE receptors.

PubMed

Sakai, Shota; Sugawara, Tatsuya; Matsubara, Kiminori; Hirata, Takashi

2009-10-09

Carotenoids have been demonstrated to possess antioxidative and anti-inflammatory effects. However, there is no report that the effects of carotenoids on degranulation of mast cell is critical for type I allergy. In this study, we focused on the effect of carotenoids on antigen-induced degranulation of mast cells. Fucoxanthin, astaxanthin, zeaxanthin, and beta-carotene significantly inhibited the antigen-induced release of beta-hexosaminidase in rat basophilic leukemia 2H3 cells and mouse bone marrow-derived mast cells. Those carotenoids also inhibited antigen-induced aggregation of the high affinity IgE receptor (Fc epsilonRI), which is the most upstream of the degranulating signals of mast cells. Furthermore, carotenoids inhibited Fc epsilonRI-mediated intracellular signaling, such as phosphorylation of Lyn kinase and Fyn kinase. It suggests that the inhibitory effect of carotenoids on the degranulation of mast cells were mainly due to suppressing the aggregation of Fc epsilonRI followed by intracellular signaling. In addition, those carotenoids inhibited antigen-induced translocation of Fc epsilonRI to lipid rafts, which are known as platforms of the aggregation of Fc epsilonRI. We assume that carotenoids may modulate the function of lipid rafts and inhibit the translocation of Fc epsilonRI to lipid rafts. This is the first report that focused on the aggregation of Fc epsilonRI to investigate the mechanism of the inhibitory effects on the degranulation of mast cells and evaluated the functional activity of carotenoids associated with lipid rafts.

Inhibitory Effect of Carotenoids on the Degranulation of Mast Cells via Suppression of Antigen-induced Aggregation of High Affinity IgE Receptors*

PubMed Central

Sakai, Shota; Sugawara, Tatsuya; Matsubara, Kiminori; Hirata, Takashi

2009-01-01

Carotenoids have been demonstrated to possess antioxidative and anti-inflammatory effects. However, there is no report that the effects of carotenoids on degranulation of mast cell is critical for type I allergy. In this study, we focused on the effect of carotenoids on antigen-induced degranulation of mast cells. Fucoxanthin, astaxanthin, zeaxanthin, and β-carotene significantly inhibited the antigen-induced release of β-hexosaminidase in rat basophilic leukemia 2H3 cells and mouse bone marrow-derived mast cells. Those carotenoids also inhibited antigen-induced aggregation of the high affinity IgE receptor (FcϵRI), which is the most upstream of the degranulating signals of mast cells. Furthermore, carotenoids inhibited FcϵRI-mediated intracellular signaling, such as phosphorylation of Lyn kinase and Fyn kinase. It suggests that the inhibitory effect of carotenoids on the degranulation of mast cells were mainly due to suppressing the aggregation of FcϵRI followed by intracellular signaling. In addition, those carotenoids inhibited antigen-induced translocation of FcϵRI to lipid rafts, which are known as platforms of the aggregation of FcϵRI. We assume that carotenoids may modulate the function of lipid rafts and inhibit the translocation of FcϵRI to lipid rafts. This is the first report that focused on the aggregation of FcϵRI to investigate the mechanism of the inhibitory effects on the degranulation of mast cells and evaluated the functional activity of carotenoids associated with lipid rafts. PMID:19700409

A new human mast cell line expressing a functional IgE receptor converts to tumorigenic growth by KIT D816V transfection.

PubMed

Saleh, Rosine; Wedeh, Ghaith; Herrmann, Harald; Bibi, Siham; Cerny-Reiterer, Sabine; Sadovnik, Irina; Blatt, Katharina; Hadzijusufovic, Emir; Jeanningros, Sylvie; Blanc, Catherine; Legarff-Tavernier, Magali; Chapiro, Elise; Nguyen-Khac, Florence; Subra, Frédéric; Bonnemye, Patrick; Dubreuil, Patrice; Desplat, Vanessa; Merle-Béral, Hélène; Willmann, Michael; Rülicke, Thomas; Valent, Peter; Arock, Michel

2014-07-03

In systemic mastocytosis (SM), clinical problems arise from factor-independent proliferation of mast cells (MCs) and the increased release of mediators by MCs, but no human cell line model for studying MC activation in the context of SM is available. We have created a stable stem cell factor (SCF) -dependent human MC line, ROSA(KIT WT), expressing a fully functional immunoglobulin E (IgE) receptor. Transfection with KIT D816V converted ROSA(KIT WT) cells into an SCF-independent clone, ROSA(KIT D816V), which produced a mastocytosis-like disease in NSG mice. Although several signaling pathways were activated, ROSA(KIT D816V) did not exhibit an increased, but did exhibit a decreased responsiveness to IgE-dependent stimuli. Moreover, NSG mice bearing ROSA(KIT D816V)-derived tumors did not show mediator-related symptoms, and KIT D816V-positive MCs obtained from patients with SM did not show increased IgE-dependent histamine release or CD63 upregulation. Our data show that KIT D816V is a disease-propagating oncoprotein, but it does not activate MCs to release proinflammatory mediators, which may explain why mediator-related symptoms in SM occur preferentially in the context of a coexisting allergy. ROSA(KIT D816V) may provide a valuable tool for studying the pathogenesis of mastocytosis and should facilitate the development of novel drugs for treating SM patients. © 2014 by The American Society of Hematology.

Specific IgE for Fag e 3 Predicts Oral Buckwheat Food Challenge Test Results and Anaphylaxis: A Pilot Study.

PubMed

Yanagida, Noriyuki; Sato, Sakura; Maruyama, Nobuyuki; Takahashi, Kyohei; Nagakura, Ken-Ichi; Ogura, Kiyotake; Asaumi, Tomoyuki; Ebisawa, Motohiro

2018-01-01

Buckwheat (BW) is the source of a life-threatening allergen. Fag e 3-specific serum IgE (sIgE) is more useful than BW-sIgE for diagnosis; however, it is unknown whether Fag e 3-sIgE can predict oral food challenge (OFC) results and anaphylaxis. This study aimed to clarify the efficacy of Fag e 3-sIgE in predicting OFC results and anaphylaxis. We conducted a retrospective review of BW- and Fag e 3-sIgE data obtained using the ImmunoCAP® assay system and fluorescent enzyme-linked immunosorbent assay from children who underwent OFC using 3,072 mg of BW protein between July 2006 and March 2014 at Sagamihara National Hospital, Kanagawa, Japan. We analyzed 60 patients aged 1.9-13.4 years (median 6.0 years); 20 (33%) showed objective symptoms upon BW OFC. The patients without symptoms had significantly lower Fag e 3-sIgE than those with non-anaphylactic (p < 0.001) and anaphylactic reactions to BW (p = 0.004). Fag e 3-sIgE was the only tested factor that significantly predicted positive OFC results (odds ratio 8.93, 95% confidence interval 3.10-25.73, p < 0.001) and OFC-induced anaphylaxis (2.67, 1.12-6.35, p = 0.027). We suggest that a threshold Fag e 3-sIgE level of 18.0 kUE/L has 95% probability of provoking a positive reaction to BW. Fag e 3-sIgE predicted OFC results and OFC-induced anaphylaxis. We further emphasize paying careful attention to the risk of BW OFC-induced anaphylaxis. © 2018 The Author(s) Published by S. Karger AG, Basel.

IL-33 and IgE stimulate mast cell production of IL-2 and regulatory T cell expansion in allergic dermatitis.

PubMed

Salamon, P; Shefler, I; Moshkovits, I; Munitz, A; Horwitz Klotzman, D; Mekori, Y A; Hershko, A Y

2017-11-01

We have previously shown that mast cells (MCs) suppress chronic allergic dermatitis in mice. The underlying mechanism involves MC-derived IL-2, which supports regulatory T cell (Treg) response at the site of inflammation. However, it is not clear what are the factors that drive MCs to produce IL-2. To understand the mechanisms that lead to IL-2 production from MCs in chronic allergic dermatitis. Isolated murine bone marrow-derived MCs (BMMCs) were incubated with various stimulators, and IL-2 production was assessed by RT-PCR and ELISA. The response of signalling pathways was evaluated by MAPK inhibitors and Western blot analysis. The effect of MC-IL-2 on Tregs was studied by incubation of splenic T cells with conditioned media obtained from activated BMMCs. Dermatitis was elicited by repeated exposures of mouse ears to oxazolone. MCs in mouse and human skin samples were evaluated by immunostaining. BMMCs released IL-2 in response to IL-33, and IL-2 production was further enhanced by concomitant FcεRI activation. The effect of IL-33 was mediated by activation of the MAPK family members. IL-2 in conditioned media from IL-33 and IgE-stimulated BMMCs led to considerable expansion of Tregs in vitro. IL-33 levels were elevated in oxazolone-challenged ears along with increased numbers of IL-2-expressing MCs. Human skin with chronic inflammation also contained IL-2-expressing MCs that colocalized with IL-33 staining in the dermis. IL-33, in collaboration with IgE, is critical for MC-IL-2 production in allergic skin disease, thus leading to Treg stimulation and suppression of allergic dermatitis. © 2017 John Wiley & Sons Ltd.

Generation and functional analysis of T cell lines and clones specific for schistosomula released products (SRP-A).

PubMed

Damonneville, M; Velge, F; Verwaerde, C; Pestel, J; Auriault, C; Capron, A

1987-08-01

Antigens present in the products released by the larval stage of schistosome (SRP-A) were shown to induce a strong cytotoxic and protective IgE response both in the rat and the monkey. T cell lines and clones specific for SRP-A or 26 kD antigens which are the main target of the cytotoxic IgE have been derived. The passive transfer of SRP-A specific T lymphocytes into infected rats led to an increase of the IgE response, conferring a significant level of protection to the rats. In coculture assays in vitro, these cell lines significantly enhanced the production of IgE by SRP-A sensitized rat spleen cells. This helper effect on the IgE response was confirmed with 26 kD T cell clone supernatants. Moreover, supernatants obtained after stimulation with phorbol myristate acetate were able to enhance the IgE production of a hybridoma B cell line (B48-14) producing a monoclonal IgE antibody, cytotoxic for the schistosomula.

Regulation and dysregulation of immunoglobulin E: a molecular and clinical perspective

PubMed Central

2010-01-01

Background Altered levels of Immunoglobulin E (IgE) represent a dysregulation of IgE synthesis and may be seen in a variety of immunological disorders. The object of this review is to summarize the historical and molecular aspects of IgE synthesis and the disorders associated with dysregulation of IgE production. Methods Articles published in Medline/PubMed were searched with the keyword Immunoglobulin E and specific terms such as class switch recombination, deficiency and/or specific disease conditions (atopy, neoplasia, renal disease, myeloma, etc.). The selected papers included reviews, case reports, retrospective reviews and molecular mechanisms. Studies involving both sexes and all ages were included in the analysis. Results Both very low and elevated levels of IgE may be seen in clinical practice. Major advancements have been made in our understanding of the molecular basis of IgE class switching including roles for T cells, cytokines and T regulatory (or Treg) cells in this process. Dysregulation of this process may result in either elevated IgE levels or IgE deficiency. Conclusion Evaluation of a patient with elevated IgE must involve a detailed differential diagnosis and consideration of various immunological and non-immunological disorders. The use of appropriate tests will allow the correct diagnosis to be made. This can often assist in the development of tailored treatments. PMID:20178634

Lifelong memory responses perpetuate humoral TH2 immunity and anaphylaxis in food allergy.

PubMed

Jiménez-Saiz, Rodrigo; Chu, Derek K; Mandur, Talveer S; Walker, Tina D; Gordon, Melissa E; Chaudhary, Roopali; Koenig, Joshua; Saliba, Sarah; Galipeau, Heather J; Utley, Adam; King, Irah L; Lee, Kelvin; Ettinger, Rachel; Waserman, Susan; Kolbeck, Roland; Jordana, Manel

2017-12-01

A number of food allergies (eg, fish, shellfish, and nuts) are lifelong, without any disease-transforming therapies, and unclear in their underlying immunology. Clinical manifestations of food allergy are largely mediated by IgE. Although persistent IgE titers have been attributed conventionally to long-lived IgE + plasma cells (PCs), this has not been directly and comprehensively tested. We sought to evaluate mechanisms underlying persistent IgE and allergic responses to food allergens. We used a model of peanut allergy and anaphylaxis, various knockout mice, adoptive transfer experiments, and in vitro assays to identify mechanisms underlying persistent IgE humoral immunity over almost the entire lifespan of the mouse (18-20 months). Contrary to conventional paradigms, our data show that clinically relevant lifelong IgE titers are not sustained by long-lived IgE + PCs. Instead, lifelong reactivity is conferred by allergen-specific long-lived memory B cells that replenish the IgE + PC compartment. B-cell reactivation requires allergen re-exposure and IL-4 production by CD4 T cells. We define the half-lives of antigen-specific germinal centers (23.3 days), IgE + and IgG 1 + PCs (60 and 234.4 days, respectively), and clinically relevant cell-bound IgE (67.3 days). These findings can explain lifelong food allergies observed in human subjects as the consequence of allergen exposures that recurrently activate memory B cells and identify these as a therapeutic target with disease-transforming potential. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Correlation between specific immunoglobulin E levels and the severity of reactions in egg allergic patients.

PubMed

Benhamou, Avigael H; Zamora, Samuel A; Eigenmann, Philippe A

2008-03-01

Different studies proposed specific immunoglobulin E (IgE) cut-off levels for the diagnosis of egg allergy. Little is known if IgE titres could be helpful for prediction of the severity of the reaction. The aim of this study was to determine whether IgE titres are associated with the severity of the reaction during a standardized egg challenge. We reviewed data obtained during oral challenge tests to egg performed between 2003 and 2005, and attributed a clinical score to the positive reactions. Serum specific IgE levels were analysed in relation with the severity of the reaction. We analysed data from 51 oral food challenges to egg, raw or cooked. Sixteen challenges (31%) were negative and 35 (69%) were positive of which 13 challenges (37% of positive reactions) elicited a severe reaction. IgE levels in our patients ranged from undetectable to 14.90 kU/l. We could determine a cut-off level of 8.20 kU/l for a 90% probability of clinical reactivity. IgE titres were statistically significantly different between the patients with absent, mild and moderate or severe reaction. Patients with negative challenge had IgE levels between 0.35 and 6.41 kU/l (median 1.17), those with mild and moderate reaction had IgE levels ranging from 0.35 to 14.90 (median 2.47) and patients with severe reactions had IgE between 1.18 and 11.00 (median 3.70) (p = 0.006). Our results show a correlation between IgE titres and the severity of the clinical reaction to egg. IgE titres may help to determine the potential risk of a reaction to eggs.

DOEDEF Software System, Version 2. 2: Operational instructions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meirans, L.

The DOEDEF (Department of Energy Data Exchange Format) Software System is a collection of software routines written to facilitate the manipulation of IGES (Initial Graphics Exchange Specification) data. Typically, the IGES data has been produced by the IGES processors for a Computer-Aided Design (CAD) system, and the data manipulations are user-defined ''flavoring'' operations. The DOEDEF Software System is used in conjunction with the RIM (Relational Information Management) DBMS from Boeing Computer Services (Version 7, UD18 or higher). The three major pieces of the software system are: Parser, reads an ASCII IGES file and converts it to the RIM database equivalent;more » Kernel, provides the user with IGES-oriented interface routines to the database; and Filewriter, writes the RIM database to an IGES file.« less

IgE mediated food allergy in Korean children: focused on plant food allergy.

PubMed

Lee, Soo-Young

2013-01-01

, we reveals that the peanut sensitization rate in Korea reaches 18%, and that, when sensitized to peanut, patients showed a significant tendency to have co-sensitization with house dust mites, egg white, wheat, and soybean. The higher specific IgE to peanut was related to the likelihood of the patient developing severe systemic reactions. In another study, based on the data analysis of 69 patients under 4 years of age who had suspected peanut and tree nut allergy, 22 (31.9%) were sensitized to walnut (>0.35 kU/L, 0.45-27.4 kU/L) and 6 (8.7%) experienced anaphylaxis due to a small amount of walnut exposure. Furthermore, in this review, clinical and immunological studies on plant food allergies, such as buckwheat allergy, rice allergy, barley allergy, and kiwi fruit allergy, in Korean children are discussed.

The descriptive epidemiology of house dust mite-specific and total immunoglobin E in England using a nationally representative sample.

PubMed

Court, C S; Cook, D G; Strachan, D P

2002-07-01

Previous studies have shown that IgE levels vary according to factors such as age, gender and smoking but most studies have been small and none have been based on a nationally representative sample. To investigate the influence of epidemiological factors on serum total IgE and house dust mite-specific IgE levels. An interviewer-led questionnaire was carried out and blood samples taken from 24 952 people aged 11 and over as part of the 1995 and 1996 Health Surveys for England. Serum total IgE and house dust mite-specific IgE were measured. Both total and house dust mite-specific IgE were more frequently raised in men and in younger age groups. After adjusting for age and sex, raised total IgE was more common in current smokers and non-white ethnic groups and was not related to social class. The higher levels in non-white ethnic groups was not explained by smoking, urban living or being born outside the UK. Whilst total IgE levels declined in older age groups in non-smokers, among smokers they increased across successive age groups from 50 years onwards. In contrast, following adjustment for age and sex, raised house dust mite IgE was more common in non-manual workers and in some non-white ethnic groups but was not related to smoking. This large nationwide study provides further confirmation of differing epidemiological patterns for total serum IgE and allergen-specific sensitization. Indicative ranges for 'usual' values for a wide range of ages among men and women in England are given.

Generation and functional analysis of T cell lines and clones specific for schistosomula released products (SRP-A).

PubMed Central

Damonneville, M; Velge, F; Verwaerde, C; Pestel, J; Auriault, C; Capron, A

1987-01-01

Antigens present in the products released by the larval stage of schistosome (SRP-A) were shown to induce a strong cytotoxic and protective IgE response both in the rat and the monkey. T cell lines and clones specific for SRP-A or 26 kD antigens which are the main target of the cytotoxic IgE have been derived. The passive transfer of SRP-A specific T lymphocytes into infected rats led to an increase of the IgE response, conferring a significant level of protection to the rats. In coculture assays in vitro, these cell lines significantly enhanced the production of IgE by SRP-A sensitized rat spleen cells. This helper effect on the IgE response was confirmed with 26 kD T cell clone supernatants. Moreover, supernatants obtained after stimulation with phorbol myristate acetate were able to enhance the IgE production of a hybridoma B cell line (B48-14) producing a monoclonal IgE antibody, cytotoxic for the schistosomula. PMID:3498590

Structural and Physical Basis for Anti-IgE Therapy

NASA Astrophysics Data System (ADS)

Wright, Jon D.; Chu, Hsing-Mao; Huang, Chun-Hsiang; Ma, Che; Wen Chang, Tse; Lim, Carmay

2015-06-01

Omalizumab, an anti-IgE antibody, used to treat severe allergic asthma and chronic idiopathic urticaria, binds to IgE in blood or membrane-bound on B lymphocytes but not to IgE bound to its high (FcɛRI) or low (CD23) affinity receptor. Mutagenesis studies indicate overlapping FcɛRI and omalizumab-binding sites in the Cɛ3 domain, but crystallographic studies show FcɛRI and CD23-binding sites that are far apart, so how can omalizumab block IgE from binding both receptors? We report a 2.42-Å omalizumab-Fab structure, a docked IgE-Fc/omalizumab-Fab structure consistent with available experimental data, and the free energy contributions of IgE residues to binding omalizumab, CD23, and FcɛRI. These results provide a structural and physical basis as to why omalizumab cannot bind receptor-bound IgE and why omalizumab-bound IgE cannot bind to CD23/FcɛRI. They reveal the key IgE residues and their roles in binding omalizumab, CD23, and FcɛRI.

A strong association between HLA-DR9 and gelatin allergy in the Japanese population.

PubMed

Kumagai, T; Yamanaka, T; Wataya, Y; Saito, A; Okui, T; Yano, S; Tsutsumi, H; Chiba, S; Wakisaka, A

2001-04-30

The frequency of HLA class I and II phenotypes was determined among 23 patients with positive gelatin IgE, eight of whom developed anaphylaxis, 18 patients who did not have gelatin IgE but who experienced non-immediate reactions after exposure to gelatin. HLA-DR9, which is unique to Orientals, was present in 56.5% of the gelatin IgE positive patients, as compared to control population frequency of 24% (P < 0.002). In the non-immediate reaction group, who did not generate IgE, phenotype distribution resembled controls. HLA-DR9 positive individuals have a relative risk of 4.1 for developing gelatin allergy with positive IgE.

Efficacy and safety of oral desensitization in children with cow's milk allergy according to their serum specific IgE level.

PubMed

García-Ara, Carmen; Pedrosa, María; Belver, María Teresa; Martín-Muñoz, María Flor; Quirce, Santiago; Boyano-Martínez, Teresa

2013-04-01

Oral desensitization in children allergic to cow's milk proteins is not risk free. The analysis of factors that may influence the outcome is of utmost importance. To analyze the efficacy and safety of the oral desensitization according to specific IgE (sIgE) level and adverse events during the maintenance phase. Thirty-six patients allergic to cow's milk (mean age, 7 years) were included in an oral desensitization protocol. Patients were grouped according to sIgE levels (ImmunoCAP) into groups 1 (sIgE <3.5 kU/L), 2 (3.5-17 kU/L), and 3 (>17-50 kU/L). Nineteen children were included as a control group. Serum sIgE levels to cow's milk and its proteins were determined at inclusion and 6 and 12 months after finishing the desensitization protocol. Thirty-three of 36 patients were successfully desensitized (200 mL): 100% of group 1 and 88% of groups 2 and 3. Desensitization was achieved in a median of 3 months (range, 1-12 months); 90% of the patients in group 1, 50% of the patients in group 2, and 30% of the patients in group 3 achieved tolerance in less than 3 months (P = .04). In the control group only 1 child tolerated milk in oral food challenge after 1 year. During the induction phase, there were 53 adverse events in 27 patients (75%). Patients of groups 2 and 3 had more severe adverse events compared with group 1. During the maintenance phase, 20 of 33 patients (60%) had an adverse event. Oral desensitization is efficacious. Tolerance is achieved earlier when sIgE is lower. Severe adverse events are frequent, especially in patients with higher sIgE levels. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Expression, purification and characterization of the recombinant chimeric IgE Fc-fragment opossum-human-opossum (OSO), an active immunotherapeutic vaccine component.

PubMed

Xu, Bingze; Lundgren, Mats; Magnusson, Ann-Christine; Fuentes, Alexis

2010-11-01

The active vaccine component recombinant chimeric IgE Fc-fragment opossum-human-opossum (OSO) has been expressed in CHO-K1 cells. It contains two identical polypeptide chains with 338 amino acid residues in each chain connected by two disulfide bridges. The cell lines were adapted to suspension culture in a serum-free medium. An expression level of 60 mg/L was obtained after 8 days in a shaking flask at a temperature of 31.5 degrees C. The OSO protein has been purified to homogeneity by a combination of three chromatographic steps. Virus inactivation and reduction by solvent detergent treatment and nano-filtration were included in the process. The residual host cell protein content was less than 50 ng/mg OSO as analyzed by ELISA. Purity was analyzed by SDS-PAGE under reducing and non-reducing conditions and was estimated by densitometry to be above 99.0%. The dimer content was less than 0.1% as estimated by analytical size exclusion chromatography. The molecular mass, as estimated by SDS-PAGE, is 90 kDa. A value of around 74 kDa was calculated from its amino acid composition. This indicates that the protein is heavily glycosylated containing around 18% carbohydrate. Isoelectric focusing in polyacrylamide gel disclosed a ladder type band pattern with pI values in the pH-range 7.0-8.3, indicating a variation in the sialic acid content. The OSO protein is not stable at temperatures above 40 degrees C and at pH values below 4 indicating that virus inactivation by incubating the protein solution at higher temperature or at lower pH is not possible. Copyright 2010 Elsevier Inc. All rights reserved.

Cephalosporin and penicillin cross-reactivity in patients allergic to penicillins.

PubMed

Liu, X-D; Gao, N; Qiao, H-L

2011-03-01

Bata-lactam antibiotics are the most commonly used antibiotics which usually cause serious IgE-mediated allergic reactions. Of all bata-lactam antibiotics, penicillins have so far been the best-studied, but the studies of cephalosporins and their cross-reactivity with penicillins are rare. We sought to evaluate the IgE response in vitro and estimate cross-reactivity between penicillins and cephalosporins in patients allergic to penicillins. We studied 87 control subjects and 420 subjects allergic to penicillins. Radioallergosorbent test (RAST) was performed to detect eight types of specific-penicillin IgE and eleven types of specific-cephalosporin IgE. The cross-reactivity and different molecules recognition by IgE were studied with a radioallergosorbent inhibition test. Of 420 patients allergic to penicillins, 95 patients (22.62%) showed specific-cephalosporin IgE positive, 73 patients (17.38%) showed IgEs positive to both penicillins and cephalosporins. In specific-penicillin IgE positive group, the positive rate of specific-cephalosporin IgE was significantly higher than in specific-penicillin IgE negative group (27.14% vs. 14.57%, p < 0.01). In urticaria group, the positive rate of specific-cephalosporin IgE was significantly higher than in other symptoms group (30.65% vs. 8.11%, p < 0.05). The analysis of drugs which have the same or similar side-chains showed that benzylpenicillanyl-IgE (BPA-IgE), ampicillanyl-IgE (APA-IgE), amoxicillanyl-IgE (AXA-IgE) were respectively related to cephalothanyl-IgE (CLA-IgE), cephalexanyl-IgE (CEXA-IgE), cephalexanyl-IgE (CEXA-IgE)in sera of penicillin-allergic patients we studied, and compared with patients who had negative amoxicillin-IgE, the positive rates of specific-ampicillin IgE and specific-cephalexin IgE were significantly higher in patients who had positive amoxicillin-IgE (14.43% vs. 3.72%, 14.00% vs. 2.96%, p < 0.01). Radioallergosorbent test and radioallergosorbent inhibition test confirmed that both nuclear

Relationships among Prenatal Aeroallergen Exposure, Maternal and Cord Blood Immunoglobulin E: Project ACCESS

PubMed Central

Peters, Junenette L.; Suglia, Shakira Franco; Platts-Mills, Thomas A.E.; Hosen, Jacob; Gold, Diane R.; Wright, Rosalind J.

2009-01-01

Background While some evidence suggests that antigen sensitization may begin prenatally, the influence of maternal allergen exposure during pregnancy has not been fully elucidated. Objectives We examined the relationship between prenatal maternal aeroallergen exposure and cord blood total immunoglobulin E (IgE) and the potential mediating/indirect effect of maternal immune response. Methods This study was performed in 301 mother-infant pairs enrolled in the Asthma Coalition on Community, Environment, and Social Stress (ACCESS) project, a study examining the effects of prenatal and early life social and physical environmental exposures on urban asthma risk. Dust samples collected prenatally from mothers’ bedrooms were analyzed for cockroach and dust mite allergens. Cord blood was analyzed for total IgE and maternal serum collected during pregnancy for total and specific IgE. We assessed the relationship between prenatal exposure and cord blood total IgE and the potential mediation effect adjusting for maternal age, race, education, smoking status and dust collection season; and child’s gender and season of birth. Results In multivariate models, elevated prenatal dust mite levels (> 0.2 µg/g) increased cord blood IgE concentrations by 29% (p=0.08) and continuous dust mite concentration was associated with a significant non-linear increase in cord blood IgE (p=0.02). Elevated prenatal exposure to cockroach allergen (> 2 U/g) was not associated with cord blood IgE, but showed a significant indirect relationship through maternal total IgE (β=0.23; 95% CI: 0.08, 0.41). Conclusions These results demonstrate that maternal prenatal exposure to household allergens may impact cord blood IgE albeit the underlying mechanism may be allergen-specific. Clinical Implications Maternal prenatal inhalant allergen exposure may precipitate infant immune response although the pathway of the effect may differ by allergen. Capsule Summary Prenatal exposure to dust mite was associated

Technological Innovations for High-Throughput Approaches to In Vitro Allergy Diagnosis.

PubMed

Chapman, Martin D; Wuenschmann, Sabina; King, Eva; Pomés, Anna

2015-07-01

Allergy diagnostics is being transformed by the advent of in vitro IgE testing using purified allergen molecules, combined with multiplex technology and biosensors, to deliver discriminating, sensitive, and high-throughput molecular diagnostics at the point of care. Essential elements of IgE molecular diagnostics are purified natural or recombinant allergens with defined purity and IgE reactivity, planar or bead-based multiplex systems to enable IgE to multiple allergens to be measured simultaneously, and, most recently, nanotechnology-based biosensors that facilitate rapid reaction rates and delivery of test results via mobile devices. Molecular diagnostics relies on measurement of IgE to purified allergens, the "active ingredients" of allergenic extracts. Typically, this involves measuring IgE to multiple allergens which is facilitated by multiplex technology and biosensors. The technology differentiates between clinically significant cross-reactive allergens (which could not be deduced by conventional IgE assays using allergenic extracts) and provides better diagnostic outcomes. Purified allergens are manufactured under good laboratory practice and validated using protein chemistry, mass spectrometry, and IgE antibody binding. Recently, multiple allergens (from dog) were expressed as a single molecule with high diagnostic efficacy. Challenges faced by molecular allergy diagnostic companies include generation of large panels of purified allergens with known diagnostic efficacy, access to flexible and robust array or sensor technology, and, importantly, access to well-defined serum panels form allergic patients for product development and validation. Innovations in IgE molecular diagnostics are rapidly being brought to market and will strengthen allergy testing at the point of care.

Sensitization to human milk.

PubMed

Schulmeister, U; Swoboda, I; Quirce, S; de la Hoz, B; Ollert, M; Pauli, G; Valenta, R; Spitzauer, S

2008-01-01

Allergy to milk is one of the earliest manifestations of IgE-mediated allergies and affects about 2.5% of newborn children. Several reports indicate that milk-allergic patients may be sensitized also to human milk proteins. To analyse the specificity and possible biological relevance of IgE reactivity to human milk antigens in milk-allergic patients. The specificity of IgE reactivity to cow's milk and human milk antigens was analysed with sera from milk-allergic children and adults by IgE immunoblotting. IgE cross-reactivity between milk antigens was studied by immunoblot inhibition experiments. That IgE reactivity to human milk antigens is not due to alloreactivity or due to the transmission of foreign antigens into mother's milk was demonstrated through the analysis of milk samples from genetically unrelated mothers before and after intake of dietary milk products. The biological relevance of IgE reactivity to human milk was confirmed by skin testing. Results IgE antibodies to human milk were found in more than 80% of the tested milk-allergic patients. Cross-reactive IgE-reactive human antigens such as alpha-lactalbumin and non-cross-reactive human milk antigens were identified. Immediate-type skin reactions could be elicited with human milk samples in patients with IgE reactivity to human milk. IgE reactivity to human milk in milk-allergic patients can be due to cross- sensitization and genuine sensitization to human milk and may cause allergic symptoms. IgE-mediated sensitization to human milk is common in milk-allergic patients and may require diagnostic testing and monitoring.

Drug allergens and food—the cetuximab and galactose-α-1,3-galactose story

PubMed Central

Berg, Emily A.; Platts-Mills, Thomas A.E.; Commins, Scott P.

2014-01-01

Objective A novel form of food allergy has been described that initially became apparent from IgE reactivity with the drug cetuximab. Ongoing work regarding the etiology, distribution, clinical management, and cellular mechanisms of the IgE response to the oligosaccharide galactose-α-1,3-galactose (α-gal) is reviewed. Data Sources Brief review of the relevant literature in peer-reviewed journals. Study Selection Studies on the clinical and immunologic features, pathogenesis, epidemiology, laboratory evaluation, and management of IgE to α-gal are included in this review. Results Recent work has identified a novel IgE antibody response to the mammalian oligosaccharide epitope, α-gal, that has been associated with 2 distinct forms of anaphylaxis: (1) immediate-onset anaphylaxis during first exposure to intravenous cetuximab and (2) delayed-onset anaphylaxis 3 to 6 hours after ingestion of mammalian food products (eg, beef and pork). Study results have suggested that tick bites are a cause of IgE antibody responses to α-gal in the United States. Patients with IgE antibody to α-gal continue to emerge, and, increasingly, these cases involve children. Nevertheless, this IgE antibody response does not appear to pose a risk for asthma but may impair diagnostic testing in some situations. Conclusion The practicing physician should understand the symptoms, evaluation, and management when diagnosing delayed allergic reactions to mammalian meat from IgE to α-gal or when initiating treatment with cetuximab in patients who have developed an IgE antibody response to α-gal. PMID:24468247

Occupational allergy to flowers: immunoblot analysis of allergens in freesia, gerbera and chrysanthemum pollen.

PubMed

van Toorenenbergen, A W

2014-10-01

High exposure to pollen from ornamental flowers can induce an IgE-mediated occupational allergy in florists and horticulture workers. We investigated IgE-binding antigens in chrysanthemum, freesia and gerbera pollen by immunoblot analysis and analysed the cross-reactivity of these pollen with birch, grass and mugwort pollen. In immunoblots with chrysanthemum pollen, major IgE-binding structures were seen with a molecular weight (MW) of approximately 25, 45 and 65 kD. In the immunoblots with freesia pollen, IgE from freesia pollen was directed against two proteins with an MW of approximately 15 kD. Most sera showed IgE binding to an approximately 15 kD band in gerbera pollen; with some sera additional bands were seen in the range of 30-50 kD. IgE binding to chrysanthemum pollen was inhibited by mugwort pollen only, whereas IgE binding to freesia pollen was suppressed by birch, grass and mugwort pollen. The inhibitory activity of birch and grass pollen extract on IgE binding to gerbera pollen extract was serum dependent and ranged from no inhibition to complete inhibition. Occupational exposure to many different flowers induced IgE against all three types of pollen. Exposure in greenhouses to gerbera flowers elicited mainly IgE against gerbera pollen. Mugwort pollen extract inhibited IgE binding to pollen from all three flowers. © 2014 John Wiley & Sons Ltd.

Cycloartenyl ferulate, a component of rice bran oil-derived gamma-oryzanol, attenuates mast cell degranulation.

PubMed

Oka, T; Fujimoto, M; Nagasaka, R; Ushio, H; Hori, M; Ozaki, H

2010-02-01

IgE-targeting therapy could provide significant progress in the treatment of allergic inflammation. In this study, we examined the effect of cycloartenyl ferulate (cycloartenol ferulic acid ester; CAF), a natural product from rice bran oil-derived gamma-oryzanol, on allergic reaction. When CAF and gamma-oryzanol were injected intradermally with anti-DNP IgE into the dorsal skin of rats, the passive cutaneous anaphylaxis reaction induced by DNP-HSA was attenuated. CAF and gamma-oryzanol also inhibited the degranulation of DNP-IgE sensitized RBL-2H3 mast cells stimulated with anti-DNP-HSA. IgE conjugated with CAF could not be detected by anti-IgE antibody in the ELISA analysis. Although incubation of IgE with CAF did not decrease the amount of IgE, it was possible to precipitate IgE by centrifugation. These results demonstrate that CAF captures IgE, prevents it from binding to FcepsilonRI, and attenuates mast cell degranulation. Copyright 2009 Elsevier GmbH. All rights reserved.

Developing a method for estimating AADT on all Louisiana roads.

DOT National Transportation Integrated Search

2015-07-01

Traffic flow volumes present key information needed for making transportation engineering and planning decisions. : Accurate traffic volume count has many applications including: roadway planning, design, air quality compliance, travel : model valida...

Abundant immunoglobulin E-positive cells in skin lesions support an allergic etiology of atopic dermatitis in the elderly

PubMed Central

Tanei, R; Hasegawa, Y; Sawabe, M

2013-01-01

Background/Objectives Atopic dermatitis (AD) in the elderly is gradually increasing in industrialized countries in association with the aging of society. We report herein four cases of elderly AD {three extrinsic [immunoglobulin (Ig)E-mediated allergy]; one intrinsic (non-IgE-allergy)} in which we investigated the presence of IgE+ cells in lesional skin. Methods/Results Single immunohistochemical and double immunofluorescence stainings were performed for skin biopsy specimens from AD patients and non-atopic control subjects with chronic eczema. In the lesional lichenified skin of patients with extrinsic elderly AD, numerous IgE+ cells were found among inflammatory cells infiltrates in the upper dermis. Comparative analysis of single immunohistochemistry results using serial paraffin and/or frozen sections found that many IgE+ cells showed identical distributions to tryptase+ mast cells. IgE+ cells coincident with CD1a+ Langerhans cells in the epidermis were found in small numbers only in frozen sections. Double immunofluorescence staining for IgE and CD11c revealed cells coexpressing IgE and CD11c with a dendritic morphology in the papillary and upper dermis. These IgE+ mast cells and IgE+ CD11c+ cells were also found in cured normal-looking skin from a patient with extrinsic elderly AD after successful treatment. Although only a few weakly positive IgE+ cells were detected, no IgE+CD11c+ cells were found in specimens from patients with intrinsic elderly AD or non-atopic chronic eczema. Conclusion IgE-mediated allergic inflammation may play an important role in the pathobiology of elderly AD, similar to other age groups of AD. PMID:22702954

Allergen cross-reactivity between Pityrosporum orbiculare and Candida albicans.

PubMed

Huang, X; Johansson, S G; Zargari, A; Nordvall, S L

1995-08-01

Pityrosporum orbiculare and Candida albicans extracts were separated by SDS-PAGE, and IgE binding was detected by immunoblotting with 21 patient sera that were RAST positive to both yeasts. Cross-wise inhibition was performed of IgE binding of a serum pool containing IgE antibodies to both yeasts. The pool was mixed with serial dilutions of P. orbiculare or C. albicans extracts, and incubated with strips containing separated allergen. IgE binding was quantified by densitometric scanning and percent inhibition was calculated as well as the respective ratios between required extract concentration for 50% inhibition in heterologous compared to homologous inhibition for each component (inhibition ratio). Ten components of P. orbiculare were detected by more than 60% of the sera. IgE binding to C. albicans was weak, and only to four bands was IgE binding detected by more than 30% of the sera. The most important C. albicans allergen was a 48-kDa band, to which IgE of half of the patient sera bound. There was little inhibition of IgE binding to P. orbiculare with C. albicans. Thus, all but three components exhibited an inhibition ratio higher than 100. The inhibition ratio of the 48-kDa C. albicans compound was 50, thus indicating some degree of cross-reactivity. Significant cross-reactivity was shown by C. albicans compounds of 18, 24, 26, 34, and 38 kDa, the inhibition ratios of which were less than 10. There was some degree of cross-reactivity between apparent protein allergens of the two yeasts, but IgE antibodies to C. albicans do not merely reflect sensitization to P. orbiculare.

TESTS TO ASSESS SENSITIZATION TO ASPERGILLUS FUMIGATUS IN CYSTIC FIBROSIS

PubMed Central

Aguiar, Simone Santana; Damaceno, Neiva; Forte, Wilma Carvalho Neves

2017-01-01

ABSTRACT Objective: To evaluate the results of the tests used to identify the IgE mediated sensitization to Aspergillus fumigatus in patients with cystic fibrosis. Methods: This is a cross-sectional descriptive study with a convenience sample of 86 patients diagnosed with cystic fibrosis in the Reference Service in Cystic Fibrosis at a tertiary teaching hospital. The following tests were performed to assess the sensitization to A. fumigatus in patients with cystic fibrosis: Total serum IgE, eosinophil count, fungus detection through oropharyngeal swab or sputum culture, serum-specific IgE, and immediate-type hypersensitivity (IgE) skin tests. We compared the results of the different tests performed. Results: In 33 (38.4%) patients with cystic fibrosis, with ages ranging from 1 to 33 years (median of 8 years), the IgE-mediated A. fumigatus sensitization test results were: in 16 patients, there was an increase in serum-specific IgE (>0.35 kU/L); in 23, skin tests were positive; and six had sensitization in both tests. We observed two patients with eosinophilia (>1,000 eosinophils/mm3) and seven with increasing total serum IgE (>1,000 IU/mL), all of whom obtained negative results in skin tests and had no IgE increase specific to A. fumigatus. A. fumigatus was not detected in oropharyngeal swabs and/or sputum culture of any patients. Conclusions: We conclude that, among the tests used to assess sensitization to A. fumigatus in cystic fibrosis patients, both serum-specific IgE and immediate-type hypersensitivity (IgE) skin tests are required. Serum eosinophilia and respiratory secretion culture were not essential in this study. PMID:28977288

Comparison of immunoglobulin E measurements on IMMULITE and ImmunoCAP in samples consisting of allergen-specific mouse-human chimeric monoclonal antibodies towards allergen extracts and four recombinant allergens.