Dominant Allergen Research Articles

Immunoproteomic characterization of Ambrosia artemisiifolia pollen allergens in canine atopic dermatitis

Canine atopic dermatitis (CAD) is an immune system disorder that affects 10–15% of the canine population. Short ragweed (Ambrosia artemisiifolia) pollen represents one of the major seasonal sources of allergenic pollen proteins in Europe, particularly in the Pannonian valley of the Balkan region. In Serbia, about 66% of atopic dogs showed a positive intradermal skin test with its pollen extract, which is second to house dust mites. Therefore, characterization of Ambrosia artemisiifolia pollen components, in terms of defining major and minor allergens that induce clinically manifested allergic reaction in dogs, is important for valid diagnosis and efficient therapy.This study has, for the first time, characterized and identified major Ambrosia artemisiifolia allergens in CAD, using an immunoproteomic approach. To assess the prevalence of specific IgE in electrophoretically separated ragweed pollen proteins, individual reactivity of sera from dogs with CAD was analyzed and compared to the reactivity of sera from healthy dogs in the non-reducing conditions, which were found optimal for specific canine IgE detection. A specific IgE band (38kDa) was recognized as the most dominant allergen in CAD, occurring in 81% of positive dog's sera. 2-D immunoblotting followed by a mass spectrometry peptide fingerprint analyses with pooled canine and human atopic sera, revealed that 38kDa major Ambrosia atremisiifolia allergens in CAD were all five isoallergens of the Amb a 1 group (antigen E), including the previously named Amb a 2 (antigen K). In contrast to canine sera, human atopic sera also recognized lower mass allergens such as the β fragment of Amb a 1 and profilins (Amb a 8 variants).The most prominent ragweed proteins in CAD, represent, as in humans, variants of all five isoallergens of the Amb a 1 group (pectate lyase): Amb a 1.0101 and its natural variant E1XUL2, Amb a 1.0202, 1.0304, 1.0402 and the natural variant of Amb a 1.0501, E1XUM0, as well as the α fragment of pollen allergen Amb a 1.0201.

Targeted editing of goat genome with modular-assembly zinc finger nucleases based on activity prediction by computational molecular modeling

Zinc finger nuclease (ZFN) technology can mediate targeted genome modification to produce transgenic animals in a high-efficient and biological-safe way. Modular assembly is a rapid, convenient and open-source method for the synthesis of ZFNs. However, this biotechnology is hampered by multistep construction, low-efficiency editing and off-target cleavage. Here we synthesized and tested six pairs of three- or four-finger ZFNs to target one site in goat beta-lactoglobulin (BLG, a dominant allergen in goat milk) gene. Homology modeling was applied to build the structure model of ZFNs to predict their editing activities targeting at goat BLG gene. Goat fibroblast cells were transfected with plasmids that encoded ZFN pairs, and genomic DNA was isolated 72 h later for genome editing efficiency assay. The results of editing efficiency assay demonstrated that ZFNs with optimal interaction modes can edit goat BLG gene more efficiently, whereas ZFNs with unexpected interaction modes showed lower activities in editing BLG gene. We concluded that modular-assembly ZFNs can provide a rapid, public-available, and easy-to-practice platform for transgenic animal research and molecular modeling would help as a useful tool for ZFNs activity prediction.

Effect of egg white fermentation with lactobacilli on IgE binding ability of egg white proteins

Egg allergy, afflicting around 1.6% to 3.2% of the total children population, is the second most common food allergy among infants and young children. The objective of this study was to determine if lactobacilli fermentation could reduce the IgE binding ability of egg white. Acidification of egg white to pH6.0 and supplementation of tryptone are necessary to grow lactobacilli in egg white. Cell counts of Lactobacillus sanfranciscensis and Lactobacillus sakei were not affected up to 96h of incubation, while that of Lactobacillus delbrueckii subsp. delbrueckii decreased rapidly at the first 24h of incubation, increased to its inoculated level at 48h, and then leveled off afterwards. The pH of fermented egg white was reduced to 5 after 48h of incubation with L. sanfranciscensis and/or L. sakei, and after 72h incubation with L. delbrueckii subsp. delbrueckii. Among three strains studied, only L. delbrueckii subsp. delbrueckii fermented egg white showed 50% reduction in IgE binding ability. No obvious protein degradation in fermented egg white proteins was detected by SDS-PAGE. The reduction of egg white IgE binding ability was attributed to ovomucoid, the dominant egg allergen, as shown the change of molecular weight analyzed by MALDI-TOF-MS, reduction of intensity of FITC labeled ovomucoid after fermentation, and the change of intensity of glycopeptides containing core+4HexNAc and core+3HexNAc. Our study demonstrated the potential of reducing egg allergy by fermentation of egg white with L. delbrueckii subsp. delbrueckii.

Innate affairs of allergens

Activation of receptors of the innate immune system is a critical step in the initiation of immune responses. It has been shown that dominant allergens have properties that could allow them to interact with toll-like and C-type lectin receptors to favour Th2-biased responses and many bind lipids and glycans that could associate with ligands to mimic pathogen-associated microbial patterns. In accord with the proposed allergen-specific innate interactions it has been shown that the immune responses to different allergens and antigens from the same source are not necessarily coordinately regulated.

Increasing the accuracy of peanut allergy diagnosis using Ara h2

<h3>Background</h3> Measurement of whole peanut-specific IgE (sIgE) is often used to confirm sensitisation but does not reliably predict allergy. Ara h2 is the dominant peanut allergen detected in 90–100% of peanut allergies. <h3>Objectives</h3> To determine whether Ara h2 testing might improve the accuracy of diagnosing peanut allergy and therefore circumvent the need for an oral food challenge (OFC). <h3>Methods</h3> Infants from the population-based HealthNuts study were skin-prick tested to determine peanut sensitisation and subsequently underwent a peanut OFC to confirm allergy status. In a stratified random sample of 200 infants (100 peanut allergic and 100 peanut tolerant), whole peanut sIgE and Ara h2 sIgE were quantified by fluorescence enzyme immunoassay. <h3>Results</h3> We report that using a combined approach of plasma sIgE testing for whole peanut sIgE followed by Ara h2 sIgE for the diagnosis of peanut allergy, the number of OFCs required are reduced by almost two-thirds. <h3>Conclusion</h3> Who le peanut IgE followed by Ara h2 sIgE testing should be considered as the preferred two-step diagnostic tool for determining peanut allergy, as we have shown greater diagnostic accuracy than either whole peanut sIgE or peanut SPT alone.

Analysis of T Cell Responses to the Major Allergens from German Cockroach: Epitope Specificity and Relationship to IgE Production

Bla g allergens are major targets of IgE responses associated with cockroach allergies. However, little is known about corresponding T cell responses, despite their potential involvement in immunopathology and the clinical efficacy of specific immunotherapy. Bioinformatic predictions of the capacity of Bla g 1, 2, 4, 5, 6, and 7 peptides to bind HLA-DR, -DP, and -DQ molecules, and PBMC responses from 30 allergic donors, identified 25 T cell epitopes. Five immunodominant epitopes accounted for more than half of the response. Bla g 5, the most dominant allergen, accounted for 65% of the response, and Bla g 6 accounted for 20%. Bla g 5 induced both IL-5 and IFN-γ responses, whereas Bla g 6 induced mostly IL-5, and, conversely, Bla g 2 induced only IFN-γ. Thus, responses to allergens within a source are independently regulated, suggesting a critical role for the allergen itself, and not extraneous stimulation from other allergens or copresented immunomodulators. In comparing Ab with T cell responses for several donor/allergen combinations, we detected IgE titers in the absence of detectable T cell responses, suggesting that unlinked T cell-B cell help might support development of IgE responses. Finally, specific immunotherapy resulted in IL-5 down modulation, which was not associated with development of IFN-γ or IL-10 responses to any of the Bla g-derived peptides. In summary, the characteristics of T cell responses to Bla g allergens appear uncorrelated with IgE responses. Monitoring these responses may therefore yield important information relevant to understanding cockroach allergies and their treatment.

Increasing the accuracy of peanut allergy diagnosis by using Ara h 2

Measurement of whole peanut-specific IgE (sIgE) is often used to confirm sensitization but does not reliably predict allergy. Ara h 2 is the dominant peanut allergen detected in 90% to 100% of patients with peanut allergy and could help improve diagnosis. We sought to determine whether Ara h 2 testing might improve the accuracy of diagnosing peanut allergy and therefore circumvent the need for an oral food challenge (OFC). Infants from the population-based HealthNuts study underwent skin prick tests to determine peanut sensitization and subsequently underwent a peanut OFC to confirm allergy status. In a stratified random sample of 200 infants (100 with peanut allergy and 100 with peanut tolerance), whole peanut sIgE and Ara h 2 sIgE levels were quantified by using fluorescence enzyme immunoassay. By using the previously published 95% positive predictive value of 15 kU(A)/L for whole peanut sIgE, a corresponding specificity of 98% (95% CI, 93% to 100%) was found in this study cohort. At the equivalent specificity of 98%, the sensitivity of Ara h 2 sIgE is 60% (95% CI, 50% to 70%), correctly identifying 60% of subjects with true peanut allergy compared with only 26% correctly identified by using whole peanut sIgE. We report that when using a combined approach of plasma sIgE testing for whole peanut followed by Ara h 2 for the diagnosis of peanut allergy, the number of OFCs required is reduced by almost two thirds. Ara h 2 plasma sIgE test levels provide higher diagnostic accuracy than whole peanut plasma sIgE levels and could be considered a new diagnostic tool to distinguish peanut allergy from peanut tolerance, which might reduce the need for an OFC.

Stable silencing of β-lactoglobulin (BLG) gene by lentivirus-mediated RNAi in goat fetal fibroblasts

β-lactoglobulin (BLG), a dominant allergen in goat milk, is difficult to remove by traditional biochemical methods. Its elimination from goat milk by genetic modification therefore poses a major challenge for modern goat breeders. A shRNA targeting BLG mRNA with high interference efficiency was identified, with which lentiviral vectors were used for mediating stable shRNA interference in goat-fetal fibroblast cells. Apart from high efficiency in the knockdown of BLG expression in these cells, lentivector-mediated RNAi manifested stable integration into the goat genome itself. Consequently, an in vitro model for goat BLG-content control was compiled, and a goat-cell line for accompanying transgenetic goat production created.

Oral immunotherapy with immunodominant T‐cell epitope peptides alleviates allergic reactions in a Balb/c mouse model of egg allergy

Allergen-specific T-cell epitopes are obvious targets for immunotherapeutic interventions in allergic disease. T-cell epitope peptides given orally may provide a practical way of inducing tolerance and preventing allergy. This study investigates oral immunotherapy (OIT) with T-cell epitope peptides of the dominant egg-white allergen ovomucoid (Ovm) in a Balb/c mouse model of egg allergy. Groups of mice were orally sensitized to Ovm and subsequently administered Ovm T-cell epitopes [single peptide 157-171 (SP) or multiple peptide (157-171)(3) (MP)], followed by oral challenge with Ovm. Outcomes post oral challenge were measured as clinical signs, serum histamine, antibody activity (IgG, IgE, IgG1, IgG2, IgA), cytokines (IL-4, IFN-γ, IL-12p70, IL-10, TGF-β, and IL-17), and T regulatory cells (Tregs). Clinical signs were less frequent in both SP and MP groups (P ≤ 0.05). Specific IgE was less and IgA was more in both groups; however, SP-treated mice had less histamine and IgG1 and more IgG2-related antibodies indicating a bias toward the type-1 response (P ≤ 0.05). Concentration of type-2 cytokine interleukin-4 (IL-4) was significantly less in both groups and IL-12p70 and IL-10 were more in SP-treated mice (P ≤ 0.001). Interferon-γ, IL-17, and TGF-β did not differ significantly. There was significant increase in the percentage of CD4+FOXP3+ and CD4+CD25+ cells in the SP group, indicating the significant role of Tregs in immune regulation. In summary, we demonstrated that OIT with SP and MP comprising the immunodominant regions of Ovm was safe and significantly reduced subsequent frequency of allergy to Ovm, and validated potential use of Ovm T-cell epitope as an immunoregulator.

Broad Aberration In The Humoral Immune Responses To An Aeroallergen

RATIONALE: Mountain cedar sensitive patient produce IgE antibodies (Abs) to both conformational and linear epitopes of the dominant allergen, Jun a 1. We compared the serum IgE, IgG and IgA responses to linear and conformational epitopes to asses the structural forms that induce these responses.

Anaphylaxis to hyperallergenic functional foods

BackgroundFood allergy can cause life threatening reactions. Currently, patients with severe food allergy are advised to avoid foods which provoke allergic reactions. This has become increasingly difficult as food proteins are being added to a broader range of consumer products.Patients and methodsHere we describe our investigations into the allergenicity of a new drink when two cow's milk allergic children suffered anaphylaxis after consuming Wh2ole®.ResultsOur studies have shown that in comparison with cow's milk, Wh2ole® contains at least three times the concentration of β-lactoglobulin. β-lactoglobulin is one of the dominant allergens in bovine milk.ConclusionsThese studies have shown that modern technology allows the creation of "hyperallergenic" foods. These products have the potential to cause severe reactions in milk allergic persons. Avoiding inadvertent exposure is the shared responsibility of allergic consumers, regulatory authorities and the food industry.

Clinical reactivity to raw peanut correlates with IgE binding to conformational epitopes of Ara h 1: a Case Report

Most peanut allergic individuals have reactivity to the dominant allergens, Ara h 1, 2 or 3, and a limited number of that promote IgE of responses (1). While IgE recognition of aeroallergens is frequently against conformational epitopes, the responses to peanuts, and foods in general, is toward linear epitopes (2). Conformational epitopes to foods, mainly egg or milk, are actually associated with development of tolerance (3). Conversely, reactivity to linear epitopes is associated with food allergy persistence (4). Here, we report data on an unusual case of peanut allergy that supports IgE-mediated clinical reactivity to conformational epitopes in Ara h1. We show specific IgE reactivity to Ara h1 in peanut that is because of conformational epitopes. A 35-year-old male patient with a clinical history of chronic nasal congestion, intermittent postnasal drip, ocular pruritus increased in Spring and Fall or with cat exposure, and oral pruritus to several foods presented for allergic evaluation. The oral pruritus, similar in presentation to oral allergy syndrome (OAS), was often accompanied by tongue swelling but not with difficulty breathing and occurred with uncooked tree nuts and uncooked peanuts. He had similar symptoms in the past with banana. Surprizingly, he reported not having these symptoms when eating food products in which the peanuts had been cooked. He was found to be highly reactive upon skin testing to the following allergens: peanut, brazil nut, almond, hazelnut, pecan, pistachio, and pine nut, as well as trees, grasses, ragweed, mold, house dust mite and cat, but negative to cashew and walnut. He was found to have a peanut-specific IgE titer of 5.5 kU/l. To test whether reactivity was being lost upon heating, whole peanut extract was heated to boiling and immunoblotted using the patient's serum. IgE reactivity was detected using HRP-conjugated anti-human IgE. Oral allergy syndrome has been reported to associate with reactivity toward the relatively unstable 16- to 17-kD-sized Ara h 8 protein (5). While we did observe a heat-affected protein at this size, as well as an additional band at approximately 20 kD, Fig. 1A demonstrates that the reactivity to another specific band at approximately 60 kDa was rapidly lost upon boiling, while most others were unaffected. To identify this protein, we performed two-dimensional protein analysis on raw, whole peanut extracts and resolved this into a number of potential protein spots (Fig. 1B). Six potential proteins were selected for mass spectrometry-based identification based on immunoblotting of the protein map using the patients serum and included one protein of a size that was unaffected by boiling (Fig. 1B). The protein identities showed that spots 2–6 all contained the major peanut allergen Ara h 1 while protein spot 1 was Arachin 6. We utilized a peptide array-based immunoassay of sequential linear epitopes for Ara h1, 2 and 3, as we have previously described and shown to correlate with symptom severity (1) and found no IgE recognition of linear epitopes of Ara h1, 2 or 3. Figure 1 (A) IgE reactivity to peanut proteins is rapidly lost upon boiling. Whole peanut protein was boiled for the indicated times and immunoblotted using the patient's sera. Anti-human IgE was used to detect IgE reactivity. (B) Two-dimensional analysis of peanut ... Thermal processing has been the subject of a number of studies, in large part because of the dietary differences in peanut consumption between westernized and other societies. Some report reductions in the IgE-binding capacity of several peanut proteins, including Ara h 1 (6, 7). However, these studies show relatively small reductions and only after long periods of boiling (>20 min). This response is highly suggestive of a conformational epitope or reactivity toward a secondary modification, such as glycosylation or phosphorylation. However, two-dimensional resolution discriminates proteins with different modifications and because the patient's IgE showed reactivity toward six different modifications of Ara h 1, it is most likely that a conformational epitope is involved. In conclusion, we report a patient with novel form of peanut allergy, wherein IgE reactivity is rapidly lost upon cooking and symptoms are dominated by oral pruritus. We demonstrate that this reactivity is to Ara h 1 but believe it is against a conformational epitope, which has not been reported before for peanut allergens.

Molecular mimicry as the key to the dominance of the house dust mite allergen Der p 2

Evaluation of: Trompette A, Divanovic S, Visintin A et al. Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein. Nature 457, 585–588 (2009).The majority of complex sources of allergen contain a small number of dominant allergens that bind at least half of the IgE antibodies of allergic subjects. For the house dust mite Dermatophagoides pteronyssinus, these allergens are Der p 1 and Der p 2. There is evidence that the cysteine-protease activity of Der p 1 imparts adjuvant activity to the allergen. It has now been shown that Der p 2 mimics the activity of its fellow ML-domain protein, MD-2, by presenting lipopolysaccharide to Toll-like receptor-4 for the activation of inflammatory genes. In accord with this, Der p 2 presented with lipopolysaccharide also induced enhanced type 1 allergic sensitization of mice, even when they were deficient in MD-2. The mimicry of MD-2 can thus also self adjuvant Der p 2 to enhance it allergenicity. This not only describes an intriguing mechanism for enhancing allergenicity but also, since both of the dominant mite allergens have intrinsic adjuvant activity, exemplifies an important principle for driving allergic sensitization.

Determinants of indoor allergens in tropical child care centers

Limited data are available about indoor allergen determinants in child care centers (CCCs) especially in the tropics. This information is important epidemiologically and clinically considering many children attend CCCs. The purpose of this study was to determine the allergen concentrations in CCCs and their associations with CCC characteristics and indoor air quality (IAQ). A panel of indoor allergens including Der p 1, Blo t 5, Fel d 1, Can f 1, Mus m 1, Bla g 1 and Asp f 1 were evaluated from dusts vacuumed from classroom floors of CCCs. Allergen levels were assayed with antibody-based bioplex array or enzyme-linked immunosorbent assays. Indoor temperature, relative humidity and air exchange rates were measured and CCC characteristics inspected. Allergen levels were linearly regressed with CCC characteristics and IAQ. The dominant allergens found in classroom floors were Der p 1, Blo t 5 and Fel d 1. Lower indoor temperatures were associated with higher Der p 1 while lower ventilation rates were associated with higher Blo t 5 concentrations. Prevalence of cat owners was found to be a predictor for Fel d 1 concentrations. Full or partial carpeting is associated with higher dust mite allergen levels. These findings provide information for future indoor allergen exposure assessment studies in CCCs and can be used for intervention with regard to allergen avoidance.

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

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.

Recent Advances in the Understanding of Egg Allergens: Basic, Industrial, and Clinical Perspectives

The emergence of egg allergy has had both industrial and clinical implications. In industrialized countries, egg allergy accounts for one of the most prevalent food hypersensitivities, especially in children. Atopic dermatitis represents the most common clinical manifestation in infancy; however, the range of clinical signs is broad and encompasses life-threatening anaphylaxis. The dominant egg allergens are proteins and are mainly present in the egg white, for example, ovalbumin, ovomucoid, ovotransferrin, and lysozyme. However, egg yolk also displays low-level allergenicity, for example, alpha-livetin. Strict avoidance of the offending food remains the most common recommendation for egg-allergic individuals. Nevertheless, the omnipresence of egg-derived components in prepackaged or prepared foods makes it difficult. Therefore, more efficient preventive approaches are investigated to protect consumers from inadvertent exposure and ensuing adverse reactions. On the one hand, commercial kits have become readily available that allow for the detection of egg contaminants at trace levels. On the other hand, attempts to produce hypoallergenic egg-containing products through food-processing techniques have met with promising results, but the approach is limited due to its potentially undesirable effects on the unique functional and sensory attributes of egg proteins. Therefore, the development of preventive or curative strategies for egg allergy remains strongly warranted. Pilot studies have suggested that oral immunotherapy (IT) with raw or cooked preparations of egg may represent a safe alternative, immediately available to allergic subjects, but remains applicable to only nonanaphylactic patients. Due to the limitations of conventional IT, novel forms of immunotherapy are sought based on information obtained from the molecular characterization of major egg allergens. In the past decade, promising approaches to the treatment and prevention of egg allergy have been explored and include, among others, the production of hypoallergenic recombinant egg proteins, the development of customized peptides, and bacterial-mediated immunotherapy. Nonspecific approaches have also been evaluated, and preliminary trials with the use of probiotic bacteria have yielded encouraging results. The current understanding of egg allergens offers novel approaches toward the making of food products safe for human consumption and the development of efficient immunotherapeutic strategies.

In Adults with High Grass Pollen Exposure, Specific IgE Antibody to Grass is Related to Total IgE and Wheezing

Increased total IgE is associated with the diagnosis of asthma and acute episodes requiring emergency treatment. To determine whether IgE antibody (ab) to grass contributes to total IgE when grass is the dominant allergen, we investigated a population of patients during the pollen season in northern California.

Natural rubber latex and chestnut allergy: cross-reactivity or co-sensitization?

Chestnut and natural rubber latex (NRL) allergy are often associated in the latex-fruit syndrome. To establish whether the concurrent NRL and chestnut IgE antibody reactivity are the results of co-sensitization or cross-reactivity. Sera from 19 patients with chestnut- and NRL-specific IgE were selected and tested for reactivity with recombinant (r) latex allergens. Cross-reactivity was explored by IgE-inhibition experiments using chestnut or NRL allergens as solid phase on ImmunoCAP. IgE-antibodies were detected to rHev b 6.01 (prohevein) in 58% of the sera, to rHev b 5 in 32%, to rHev b 12 in four of 13 sera, to rHev b 7.02 and rHev b 11 in four, and to rHev b 1 in two of 19 sera. rHev b 8-IgE antibodies were found in nine sera (47%), whereas six displayed mono-sensitization to rHev b 8 with regard to our test panel. Three of 16 sera showed IgE to cross-reactive carbohydrate determinants. In most sera recognizing rHev b 5 and/or rHev b 6.01 as major allergens the IgE-reactivity to NRL remained unaffected by chestnut extract and chestnut-IgE remained unaffected by NRL extract. Conversely, in sera with rHev b 8 as dominant allergen IgE-binding to NRL was nearly completely inhibited by chestnut and vice versa. IgE-binding to rHev b 8 was abolished by chestnut extract. Although patients have concomitant IgE antibody reactivity to chestnut and NRL, cross-reactivity could be demonstrated mainly in those patients with IgE to Hev b 8 (profilin) from NRL.

IL-5 T-cell responses to house dust mite are associated with the development of allergen-specific IgE responses and asthma in the first 5 years of life

Allergen-specific T(H)2-like cytokine responses are considered to be important in sensitization and allergic diseases. To examine the profile of house dust mite (HDM) stimulated T-cell cytokines and their relationship to allergic disease in children over the period of the first 5 years of life. Subjects with a family history of asthma who were enrolled antenatally in the Childhood Asthma Prevention Study and had skin prick tests, clinical evaluation for asthma and eczema, and in vitro assessment of lymphocyte cytokine responses to HDM extract performed at ages 18 months (n = 281), 3 years (n = 349), and 5 years (n = 370). IL-13 at 3 and 5 years and IL-5, IL-10, and IFN- gamma at 18 months, 3 years, and 5 years were measured by ELISA. House dust mite-specific cytokine responses increased with age for all cytokines except IFN-gamma. HDM-specific IL-5 responses at 3 years and 5 years were significantly positively related to skin prick test positivity at 5 years. IL-5 responses at 5 years were also significantly related to asthma at 5 years. Other HDM-specific cytokine responses were not related to asthma or eczema at 5 years. Responses were not altered by a HDM avoidance intervention. IL-5 responses to HDM, the dominant local inhalant allergen, are related to the expression of clinical illness at age 5 years. The T-cell response to HDM, as reflected in IL-5 production, is acquired over the first years of life and may play a role in the expression of allergic airways disease.

Addressing issues of asthma in inner-city children

For children living in the inner city, asthma tends to be more frequent and severe. Although the causes for this heightened severity of asthma are not clearly established, environmental allergens likely play a major role. To characterize, understand, and treat children with asthma living in the inner city better, the National Institutes of Allergy and Infectious Diseases of the National Institutes of Health established an Inner City Asthma Program in 1991. Over the past 15 years, 3 separate inner-city asthma research networks have been formed and funded by this institute. The work from these programs has led to important observations including evidence that environmental allergens, particularly cockroach, are important for sensitization and severity of asthma of the affected children. Furthermore, reductions in the allergen load can lead to improved asthma control. The most recent program, the Inner City Asthma Consortium, was formed in 2002 with a goal to develop immune-based therapy for children with asthma in the inner city and to determine mechanisms of these therapies as well as immunopathogenesis of asthma in these high-risk children. This article reviews these programs and how they have begun the effort to understand and treat children with asthma who live in inner cities better and what their findings mean in relationship to unique features of asthma in inner city children.