Allergens are foreign proteins or glycoproteins that are the target of IgE antibody responses in humans. The relationship between subsequent exposure and the allergic symptoms is often or usually obvious; however, there is increasing evidence that in asthma, atopic dermatitis and some forms of food allergy the induction of symptoms is delayed or chronic. The primary exposure to inhaled allergens is to the particles, which are capable of carrying allergens in the air. Thus, the response reﬂects not only the properties of the proteins, but also the biological properties of the other constituents of the particle. This is best understood in relation to the mite fecal particles in which the contents include many different immunologically active substances. Allergic disease ﬁrst became a major problem over 100 years ago, and for many years sensitization to pollens was the dominant form of these diseases. The rise in pediatric asthma correlates best with the move of children indoors, which started in 1960 and was primarily driven by indoor entertainment for children. While the causes of the increase are not simple they include both a major increase in sensitization to indoor allergens and the complex consequences of inactivity. Most recently, there has also been an increase in food allergy. Understanding this has required a reappraisal of the importance of the skin as a route for sensitization. Overall, understanding allergic diseases requires knowing about the sources, the particles and the routes of exposure as well as the properties of the individual allergens.
The allergenic load of house dust mite allergy is largely constituted by a few proteins with a hierarchical
pattern of allergenicity. The serodominant specificities are the group 1&2 and the group 23 faecal allergens.
The collective IgE binding to the group 1&2 allergens can measure unequivocal HDM sensitisation
better than HDM extracts although discrepancies have been found in regions with complex
acarofauna suggesting a need to investigate the specificity with allergen components. The group 4, 5,
7&21 allergens that each induce responses in about 40% of subjects are mid-tier allergens accounting for
most of the remaining IgE binding. Their titres are proportional to the concomitant responses to Der
p1&2. Group 2 allergen variants have different antibody binding. Body proteins only occasionally induce
sensitisation although a higher prevalence of binding by atopic dermatitis patients provides a new
avenue of research. A broad spectrum of IgE binding has been associated with diverse symptoms but not
with the severity of asthma which is associated with low IgG antibody. Some allergens such as the group
14 large lipid binding proteins and the recently described proteins Der f 24-33, need further investigation
but with the cognoscence that other denominated allergens have been found to be minor sensitisers
by comparative quantitative analyses. Scabies is a confounder for diagnosis with extracts,
inducing cross-reactive antibodies with Der p 4&20 as is seafood allergy with cross reactivity to Der p 10
a minor HDM allergen. The HDM genome sequence can now be used to verify allelic and paralogous
The high prevalence of Japanese cedar pollinosis in Japan is associated with a negative impact on the quality of life of patients, as well as signiﬁcant loss of productivity among the workforce in early spring, thus representing a serious social problem. Furthermore, the prevalence is increasing, and has risen by more than 10% in this decade. Cry j 1 and Cry j 2 were identiﬁed as the major allergens in Japanese cedar pollen (JCP), and in 2004, the existence of other major and minor allergens were revealed by a combi- nation of two-dimensional electrophoresis and immunoblotting analysis. Allergenome analysis identiﬁed a chitinase, a lipid transfer protein, a serine protease, and an aspartic protease as novel IgE-reactive allergens in patients with JCP allergy. Thaumatin-like protein (Cry j 3) was shown to be homologous to Jun a 3, a major allergen from mountain cedar pollen. Isoﬂavone reductase-like protein was also characterized in a study of a JCP cDNA library. The characterization of component allergens is required to clarify the sensitizer or cross-reactive elicitor allergens for component-resolved diagnosis (CRD). Increasing evidence from numerous clinical trials indicates that CRD can be used to design effective allergen-speciﬁc immunotherapy. In this review, we summarize the eight characterized JCP allergens and discuss the impact of CRD and characterization of novel allergens on allergen-speciﬁc immunotherapy.
Exposure and sensitization to fungal allergens can promote the development and worsening of allergic diseases. Although numerous species of fungi have been associated with allergic diseases in the litera ture, the signiﬁcance of fungi from the genera Alternaria, Cladosporium, Penicillium, Aspergillus, and Malassezia has been well documented. However, it should be emphasized that the contribution of different fungal allergens to allergic diseases is not identical, but species-speciﬁc.
Alternaria and Cladosporium species are considered to be important outdoor allergens, and sensiti zation and exposure to species of these genera is related to the development of asthma and rhinitis, as well as epidemics of asthma exacerbation, including life-threatening asthma exacerbation. In contrast, xerophilic species of Penicillium and Aspergillus, excluding Aspergillus fumigatus, are implicated in allergic diseases as indoor allergens. A. fumigatus has a high capacity to colonize the bronchial tract of asthmatic patients, causing severe persistent asthma and low lung function, and sometimes leading to allergic bronchopulmonary aspergillosis. Malassezia are common commensals of healthy skin, although they are also associated with atopic dermatitis, especially on the head and neck, but not with respiratory allergies. Despite its importance in the management of allergic diseases, precise recognition of species-speciﬁc IgE sensitization to fungal allergens is often challenging because the majority of fungal extracts exhibit broad cross-reactivity with taxonomically unrelated fungi. Recent progress in gene technology has contributed to the identiﬁcation of speciﬁc and cross-reactive allergen components from different fungal sources. However, data demonstrating the clinical relevance of IgE reactivity to these allergen components are still insufﬁcient.
Food allergy is an adverse immune response to certain kinds of food. Although any food can cause allergic reactions, chicken egg, cow's milk, wheat, shellﬁsh, fruit, and buckwheat account for 75% of food allergies in Japan. Allergen-speciﬁc immunoglobulin E (IgE) antibodies play a pivotal role in the devel- opment of food allergy. Recent advances in molecular biological techniques have enabled the efﬁcient analysis of food allergens. As a result, many food allergens have been identiﬁed, and their molecular structure and IgE-binding epitopes have also been identiﬁed. Studies of allergens have demonstrated that IgE antibodies speciﬁc to allergen components and/or the peptide epitopes are good indicators for the identiﬁcation of patients with food allergy, prediction of clinical severity and development of tolerance. In this review, we summarize our current knowledge regarding the allergens and IgE epitopes in the well-researched allergies to chicken egg, cow's milk, wheat, shrimp, and peanut.
Background: Global studies on asthma point to socioeconomic status as one of the main variables in terms of prevalence and disease severity in various parts of the world. Social factors related to com- munity violence have been linked to higher incidence of asthma in the current studies. This study in- vestigates the relationship between indicators of both community violence and development and hospital admissions due to asthma.
Methods: This was an analytical ecological study of multiple groups, using public databases with in- formation up until 2006. All Brazilian municipalities with more than 100,000 inhabitants were consid- ered as units of analysis. The main index used as socioeconomic indicator was the FIRJAN Index of Municipal Development (FIMD). The Index of Youth Vulnerability to Violence (IYVV) was used as in- dicators of community violence. The rate of admissions due to asthma was used as the outcome. Pear- son's correlation was used for multivariate analyses. The coefﬁcient of determination (R2) was calculated and the simple linear regression model adjusted for signiﬁcant correlations.
Results: There was an inverse correlation between asthma admissions and FIMD (r = -0.354, p < 0.001), with statistical signiﬁcance for all dimensions of the index. Admissions due to asthma were associated with the IYVV (r = 0.240, p < 0.001) and its component related to school attendance and employment (r = 0.315, p < 0.001), homicides (r = 0.112, p = 0.034), and poverty ((r = 0.303, p < 0.001).
Conclusions: There was a direct correlation between indicators of violence and rates of admission due asthma, and an inverse correlation with indicators of development. These results suggest that social detriment can act as a risk factor for hospital admissions due to asthma.
Background: The expression and functional role of CysLT2 receptors in asthma have not been clariﬁed. In this study, we evaluated CysLT2 receptors expression, and effects of CysLT2-and CysLT1 ⁄ 2-receptor an- tagonists on antigen-induced bronchoconstriction using isolated lung tissues from both asthma and non- asthma subjects.
Methods: CysLT1 and CysLT2 receptors expression in asthma and non-asthma lung tissue preparations was examined in immunohistochemistry experiments, and their functional roles in antigen-induced bronchoconstriction were assessed using ONO-6950, a dual CysLT1 ⁄ 2-receptor antagonist, montelukast, a CysLT1 receptor antagonist, and BayCysLT2RA, a CysLT2 receptor-speciﬁc antagonist.
Results: CysLT1 receptors were expressed on the bronchial smooth muscle and epithelium, and on alveolar leukocytes in 5 in 5 non-asthma subjects and 2 in 2 asthma subjects. On the other hand, although degrees of CysLT2 receptors expression were variable among the 5 non-asthma subjects, the expression in the asthma lung was detected on bronchial smooth muscle, epithelium and alveolar leu- kocytes in 2 in 2 asthma subjects. In the non-asthma specimens, antagonism of CysLT2 receptors did not affect antigen-induced bronchial contractions, even after pretreatment with the CysLT1-receptor speciﬁc antagonist, montelukast. However, in the bronchus isolated from one of the 2 asthma subjects, antag- onism of CysLT2 receptors suppressed contractions, and dual antagonism of CysLT1 and CysLT2 receptors resulted in additive inhibitory effect on anaphylactic contractions.
Conclusions: CysLT2 receptors were expressed in lung specimens isolated from asthma subjects. Acti- vation of CysLT2 receptors may contribute to antigen-induced bronchoconstriction in certain asthma population.
Background: Anaphylaxis is a serious type I allergic reaction that occurs suddenly and can result in death, but it is sometimes difﬁcult to differentiate from other diseases, and physicians must rely on symptoms alone for its diagnosis. Meanwhile, fractional exhaled nitric oxide (FeNO) concentration, used in assessing airway inﬂammation in bronchial asthma, is known to be affected by atopic disposition. The possible role of FeNO measurements was evaluated in patients with anaphylaxis.
Methods: FeNO was measured in 52 adult patients (17-78 years old, median age 41.5 years) in whom anaphylaxis occurred. These measurements were made within 24 h after onset and after about one month when the patients were symptom-free. In some of these patients, FeNO was measured a third time, two months or more after onset.
Results: The FeNO level in the 52 patients was not signiﬁcantly different in measurement made within 24 h of onset of anaphylaxis and after one month. However, excluding 9 patients who also had asthma history, the FeNO level in the remaining 43 patients decreased signiﬁcantly from within 24 h of onset (36.7 ± 27.5 ppb) to one month later (28.8 ± 19.5 ppb). Of these 43 patients, this phenomenon was evident in a group that had respiratory symptoms (31 patients), but it was not seen in a group that did not have respiratory symptoms (12 patients).
Conclusions: Elevation of FeNO was related to respiratory symptoms observed in anaphylactic patients without asthma. Although the mechanism of increased FeNO level is unclear, its usefulness for diagnosis of anaphylaxis must be examined in prospective studies.
Background: Omalizumab has demonstrated clinical beneﬁts in children with moderate to severe allergic asthma. However, no studies have been performed in Japanese asthmatic children. The aim of this study was to evaluate the efﬁcacy including free IgE suppression and safety of omalizumab in Japanese children with severe allergic asthma. The primary objective was to examine whether omalizumab decreases serum free IgE levels to less than 25 ng ⁄ ml (target level of suppression).
Methods: Thirty-eight Japanese children (6-15 years) with uncontrolled severe allergic asthma despite inhaled corticosteroids (>200 μg ⁄ day ﬂuticasone propionate or equivalent) and two or more controller therapies received add-on treatment with omalizumab in a 24-week, multicenter, uncontrolled, open- label study.
Results: The geometric mean serum free IgE level at 24 weeks was 15.6 ng ⁄ mL. Compared with baseline, total asthma symptom scores, daily activity scores and nocturnal sleep scores at 24 weeks were signif- icantly improved. The rates of asthma exacerbation and hospitalization due to asthma were reduced by 69.2% and 78.2%, respectively (p < 0.001), versus baseline. Quality-of-life scores were also signiﬁcantly improved (p < 0.001). In addition, 11 (28.9%) patients reduced the dose of any asthma controller med- ications. Thirty-six (94.7%) patients experienced at least one adverse event during the treatment period. All adverse events were mild or moderate in severity and no new safety concerns were detected. No patients discontinued the study.
Conclusions: In Japanese children with severe allergic asthma, omalizumab decreased free IgE levels to less than 25 ng ⁄ mL. Omalizumab improved asthma control and was well-tolerated, as well.
Background: If asthmatic children cannot obtain sufﬁcient control of their disease, not only do they suffer from asthma symptoms, but the daily life activities of their caregivers are also disrupted. We investigated the effectiveness of an inhaled corticosteroid (ICS) for symptom control in previously ICS-untreated school-aged asthmatic children as well as caregiver treatment satisfaction (CTS).
Methods: A multicenter, open-label, single-arm study on 12-week ICS (budesonide Turbuhaler®) monotherapy was undertaken in subjects aged 5-15 years with bronchial asthma not treated with ICS during the previous 3 months. At 0, 4, 8, and 12 weeks after start of ICS administration, Japanese Pediatric Asthma Control Program (JPAC) scores, and CTS scores were summated and lung function measured. At weeks 0 and 12, questionnaires on caregiver anxiety were also assessed.
Results: Seventy-ﬁve patients were enrolled, and 69 assessed. Ninety percent of subjects had been treated with asthma controller medication except ICS before study enrollment. JPAC score and CTS score were improved signiﬁcantly at weeks 4, 8, and 12 (p < 0.001). With regard to CTS, more than half of caregivers showed a perfect score at weeks 8 and 12. There was a signiﬁcant correlation between JPAC score and CTS score. Lung function and caregiver anxiety were also improved, and good compliance with treatment was observed during the intervention.
Conclusions: If treating ICS-untreated school-aged asthmatic children with uncontrolled symptoms, ICS monotherapy can improve CTS along with improving asthma control.