Allergology International
Online ISSN : 1440-1592
Print ISSN : 1323-8930
ISSN-L : 1323-8930
Volume 70 , Issue 3
Showing 1-24 articles out of 24 articles from the selected issue
Editorial
Invited Review Articles
Review Series: Allergens in Modern Society 2021
  • Toshihiro Osada, Mitsuhiro Okano
    2021 Volume 70 Issue 3 Pages 281-290
    Published: 2021
    Released: July 10, 2021
    JOURNAL FREE ACCESS

    Pollen from many tree species in the Cupressaceae family is a well-known cause of seasonal allergic diseases worldwide. Japanese cedar pollinosis and Japanese cypress pollinosis, which are caused by pollen from Japanese cedar (Cryptomeria japonica) and Japanese cypress (Chamaecyparis obtusa), respectively, are the most prevalent seasonal allergic diseases in Japan. Recently, the novel major Japanese cypress allergen Cha o 3 and the homologous Japanese cedar allergen Cry j cellulase were identified, and it was shown, for the first time, that cellulase in plants is allergenic. Although the allergenic components of pollen from both species exhibit high amino acid sequence identity, their pollinosis responded differently to allergen-specific immunotherapy (ASIT) using a standardized extract of Japanese cedar pollen. Pharmacotherapy and ASIT for Japanese cedar and cypress pollinosis have advanced considerably in recent years. In particular, Japanese cedar ASIT has entered a new phase, primarily in response to the generation of updated efficacy data and the development of new formulations. In this review, we focus on both Japanese cypress and cedar pollinosis, and discuss the latest findings, newly identified causative allergens, and new treatments. To manage pollinosis symptoms during spring effectively, ASIT for both Japanese cedar and Japanese cypress pollen is considered necessary.

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  • Nobuyuki Maruyama
    2021 Volume 70 Issue 3 Pages 291-302
    Published: 2021
    Released: July 10, 2021
    JOURNAL FREE ACCESS

    A large number of plant-derived food allergen components have been identified to date. Although these allergens are diverse, they often share common structural features such as numerous disulfide bonds or oligomeric structures. Furthermore, some plant-derived food allergen components cross-react with pollen allergens. Since the relationship between allergen components and clinical symptoms has been well characterized, measurements of specific IgE to these components have become useful for the accurate clinical diagnosis and selection of optimal treatment methods for various allergy-related conditions including allergy caused by plant-derived foods. Herein, I have described the types and structures of different plant allergen components and outlined the diagnosis as well as treatment strategies, including those reported recently, for such substances. Furthermore, I have also highlighted the contribution of allergen components to this field.

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  • Yuma Fukutomi, Yuji Kawakami
    2021 Volume 70 Issue 3 Pages 303-312
    Published: 2021
    Released: July 10, 2021
    JOURNAL FREE ACCESS

    Airborne insect particles have been identified as an important cause of respiratory allergies, including allergic asthma and rhinitis. In the literature, the significance of respiratory exposure to insect particles as a cause of occupational allergy has been well-documented. Indeed, many cases of occupational allergy have been reported including allergy to the larvae of flies and moths in anglers and occupationally exposed workers, to grain pests in bakers or other workers handling grains, and to crickets and/or locusts in researchers and workers in aquaculture companies. Furthermore, the prevalence of sensitization to insect allergens is considerably high among patients with asthma and/or rhinitis who are not occupationally exposed to insects, suggesting the clinical relevance of exposure to insects in indoor and outdoor environmental non-occupational settings. Exposure to cockroaches, a well-studied indoor insect, is associated with cockroach sensitization and the development and exacerbation of asthma. Booklice, another common indoor insect, were recently identified as a significant sensitizer of asthmatic patients in Japan and India, and potentially of asthma patients living in warm and humid climates around the world. Lip b 1 was identified as an allergenic protein contributing to the species-specific sensitization to booklice. Moths are considered a significant seasonal outdoor allergen and their allergens are considered to have the highest sensitization rate among Japanese patients. However, other than cockroaches, allergenic insect proteins contributing to sensitization have not been fully characterized to date.

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Review Article
  • Beatriz Cabanillas, Natalija Novak
    2021 Volume 70 Issue 3 Pages 313-318
    Published: 2021
    Released: July 10, 2021
    JOURNAL FREE ACCESS

    Adverse allergic reactions due to the administration of the vaccines developed for the protection of coronavirus disease 2019 (COVID-19) have been reported since the initiation of the vaccination campaigns. Current analyses provided by the Center for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) in the United States have estimated the rates of anaphylactic reactions in 2.5 and 11.1 per million of mRNA-1273 and BNT162b2 vaccines administered, respectively. Although rather low, such rates could have importance due to the uncommon fact that a large majority of the world population will be subjected to vaccination with the aforementioned vaccines in the following months and vaccination will most likely be necessary every season as for influenza vaccines. Health regulators have advised that any subject with a previous history of allergy to drugs or any component of the vaccines should not be vaccinated, however, certain misunderstanding exists since allergy to specific excipients in drugs and vaccines are in occasions misdiagnosed due to an absence of suspicion to specific excipients as allergenic triggers or due to inaccurate labeling or nomenclature. In this review, we provide an updated revision of the most current data regarding the anaphylactic reactions described for BNT162b2 vaccine, mRNA-1273 vaccine, and AZD1222 vaccine. We extensively describe the different excipients in the vaccines with the potential to elicit systemic allergic reactions such as polyethylene glycol (PEG), polysorbates, tromethamine/trometamol, and others and the possible immunological mechanisms involved.

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Original Articles
  • Noriko Nakamura, Yuka Kashitani, Hajime Yoshisue, Makoto Nagasaki, Tak ...
    2021 Volume 70 Issue 3 Pages 319-326
    Published: 2021
    Released: July 10, 2021
    JOURNAL FREE ACCESS
    Supplementary material

    Background: Omalizumab is approved as add-on therapy for pediatric asthma since 2013 in Japan, however, its data in clinical practice is limited. This post-marketing surveillance aimed to evaluate long-term safety and effectiveness of omalizumab in Japanese pediatric patients with severe allergic asthma in real-life setting.

    Methods: This 104-week, multicenter surveillance was conducted from September 2013 to May 2019 by central registration method. Patients with severe allergic asthma aged ≥6 and < 15 years at initiation of treatment who were first-time omalizumab users were included. The primary endpoints included incidence of adverse drug reactions and physician's Global Evaluation of Treatment Effectiveness (GETE). The secondary endpoints included incidence of serious adverse events, adverse events and adverse drug reactions of special interest and asthma exacerbation-related events.

    Results: Of the 128 patients enrolled, 127 completed the surveillance and were included for safety and effectiveness analysis. Thirteen patients experienced 20 adverse drug reactions with an incidence rate of 10.2%. The most frequent adverse drug reactions were pyrexia (2.4%) and urticaria (1.6%). In total, adverse events and serious adverse events occurred in 60 (47.2%) and 30 patients (23.6%) respectively. Two patients experienced anaphylactic reaction and 1 patient experienced type 1 hypersensitivity. 77.2% had an effective response to omalizumab according to GETE at final assessment, and frequency of all asthma exacerbation-related events decreased in post-treatment versus pre-treatment.

    Conclusions: Long-term omalizumab treatment showed no new safety signals in pediatric patients with severe allergic asthma. The observed safety and effectiveness profile was consistent with previous studies.

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  • Shinya Imamura, Ken Washio, Mayuko Mizuno, Yoshiko Oda, Atsushi Fukuna ...
    2021 Volume 70 Issue 3 Pages 327-334
    Published: 2021
    Released: July 10, 2021
    JOURNAL FREE ACCESS
    Supplementary material

    Background: Although basophils are considered to play an important role for maintenance of type 2 inflammation in atopic dermatitis (AD), studies on basophils in AD patients are limited. Some studies have reported the activation status, including CD203c and CD63, of peripheral blood basophils in AD patients.

    Methods: We examined the features of circulating basophils in AD patients, assessed cell surface marker expressions and total serum IgE, and compared basophil responsiveness to stimulation between AD patients and healthy controls (HCs). In addition, the correlations among AD severity, laboratory factors, and features of basophils were examined. Blood samples from 38 AD patients and 21 HCs were analyzed. Basophil response markers CD203c and CD63, and expression of surface-bound IgE and FcεRI on basophils were measured. CD203c and CD63 expressions induced by stimulation with anti-IgE and anti-FcεRI antibodies were measured. Clinical/laboratory factors including total serum IgE were examined for correlations with these basophil parameters.

    Results: Baseline CD203c and CD63 expression on basophils were significantly higher in AD patients compared with HCs. The CD203c/CD63 response ratio to anti-FcεRI stimulation was higher than that to anti-IgE stimulation in AD patients, but not HCs. FcεRI expression on basophils was higher in AD patients than in HCs, although surface-bound IgE on basophils was equivalent. Total serum IgE had negative correlations with surface-bound IgE and CD63 responsiveness to anti-IgE stimulation.

    Conclusions: Basophils were spontaneously activated under steady-state conditions in AD patients and responsiveness to anti-IgE stimulation was lower than in HCs. Despite high serum IgE and high basophil FcεRI expression, surface-bound IgE on basophils remained relatively low. Basophils might be suppressed or exhausted regarding FcεRI signaling via IgE in severe AD.

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  • Toshiki Fukasawa, Hayato Takahashi, Kunihiko Takahashi, Nanae Tanemura ...
    2021 Volume 70 Issue 3 Pages 335-342
    Published: 2021
    Released: July 10, 2021
    JOURNAL FREE ACCESS
    Supplementary material

    Background: Evidence for the risk and incidence of anticonvulsant-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in Japan is scarce.

    Methods: We conducted a matched case-control study using a large-scale Japanese claims database. SJS/TEN cases were identified using a claims-based algorithm developed in a previous study (sensitivity 76.9%, specificity 99.0%). Conditional logistic regression with Firth's bias correction to address an issue of rare events was used to estimate odds ratios (ORs) for SJS/TEN for each anticonvulsant use (90 days before the index date) versus non-use. 90-day cumulative incidence of SJS/TEN per 100,000 new users was calculated for 33 anticonvulsants. Causality between anticonvulsant use and SJS/TEN in each exposed case was assessed using the algorithm of drug causality for epidermal necrolysis (ALDEN) score.

    Results: From 5,114,492 subjects, we selected 71 SJS/TEN cases and 284 controls. We observed significantly increased ORs for SJS/TEN among new users of carbamazepine (OR 68.00) and lamotrigine (OR 36.00) with ALDEN scores of “probable” or higher. Cumulative incidence of SJS/TEN was 93.83 for carbamazepine and 84.33 for lamotrigine. One case newly exposed to phenytoin which developed SJS/TEN was rated “unlikely” in ALDEN causality, resulting in cumulative incidence of 66.27. Cumulative incidence of SJS/TEN was 25.23 for levetiracetam, 7.52 for clonazepam, and 1.23 for diazepam, but their ALDEN scores were “very unlikely”.

    Conclusions: This study is the first to document the differential risk of SJS/TEN for anticonvulsants in a real-world setting in Japan. Exposure to carbamazepine and lamotrigine was associated with an increased risk of SJS/TEN.

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  • Tomohito Takeshige, Norihiro Harada, Sonoko Harada, Ayako Ishimori, Yo ...
    2021 Volume 70 Issue 3 Pages 343-350
    Published: 2021
    Released: July 10, 2021
    JOURNAL FREE ACCESS
    Supplementary material

    Background: Previous reports have shown that pathogen-associated patterns (PAMPs) induce the production of interleukin (IL)-1β in macrophages. Moreover, studies using mouse models also suggest that chitin, which acts as a PAMP, induces adjuvant effects and eosinophilic infiltration in the lung. Thus, we investigated the effects of inhaled chitin in mouse models.

    Methods: We developed mouse models of inhaled chitin particle-induced airway inflammation and steroid-resistant ovalbumin (OVA)-induced airway inflammation. Some experimental groups of mice were treated additionally with dexamethasone (DEX). Murine alveolar macrophages (AMs), which were purified from bronchoalveolar lavage (BAL) fluids, were incubated with chitin, and treated with or without DEX.

    Results: The numbers of total cells, AMs, lymphocytes, eosinophils, and neutrophils among BAL-derived cells, as well as the IL-1β levels in BAL fluids and the numbers of IL-1β-positive cells in lung, were significantly increased by chitin stimulation. Airway hyperresponsiveness (AHR) was aggravated in mice of the chitin inflammation model compared to control animals. The production of IL-1β was significantly increased in murine AMs by chitin treatment, but DEX administration did not inhibit this chitin-induced IL-1β production. Furthermore, in mouse models, DEX treatment inhibited the OVA-induced airway inflammation and AHR but not the airway inflammation and AHR induced by chitin or the combination of OVA and chitin.

    Conclusions: These results suggest that inhaled chitin induces airway inflammation, AHR, and the production of IL-1β. Furthermore, our findings demonstrate for the first time that inhaled chitin induces steroid-resistant airway inflammation and AHR. Inhaled chitin may contribute to features of steroid-resistant asthma.

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  • Shogo Sakurai, Kazuki Furuhashi, Ryo Horiguchi, Fumiya Nihashi, Hideki ...
    2021 Volume 70 Issue 3 Pages 351-359
    Published: 2021
    Released: July 10, 2021
    JOURNAL FREE ACCESS
    Supplementary material

    Background: Follicular helper T (Tfh) cells represent a unique subset of helper CD4+ T cells in lymphoid follicles. Recently, Tfh cells were shown to play an important role in asthma through B cell differentiation. Conventional lung DCs are classified into two major subsets: conventional type 1 (cDC1) and type 2 (cDC2). Although the two subsets are different in driving particular T cell responses, the subset that induces Tfh cells in the asthmatic lung primarily has yet to be fully elucidated.

    Methods: We evaluated Tfh cells, defined by the expression of CD4 and CXCR5, in HDM-challenged mice. Next, we characterized cDC1 and cDC2 purified from antigen-primed lung and examined their Tfh cell-inducing capacity. Additionally, the ability of lung DC-induced Tfh cells to cause germinal center B (GCB) cells to produce antigen-specific IgE was assessed.

    Results: In HDM-challenged mice, Bcl-6-expressing Tfh cells were significantly increased in the mediastinal lymph nodes. Lung cDC2, but not lung cDC1, increased after HDM priming, and cDC2 secreted larger amounts of IL-6 with higher ICOS-L expression than cDC1. In the co-cultures with OVA-specific naïve CD4+ T cells, cDC2 from OVA-primed lung induced Bcl-6-expressing Tfh cells more efficiently, together with larger amounts of IL-6 and IL-21, than cDC1. Blockage of IL-6 or ICOS-L significantly reduced Tfh cell induction. Finally, cDC2-induced Tfh cells enabled GCB cells to produce OVA-specific IgE.

    Conclusions: In asthmatic lung, cDC2 is the primary DC subset responsible for Tfh cell differentiation and plays an important role in humoral immunity in asthma by inducing Tfh cells.

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  • Jun-ichi Kashiwakura, Mari Yoshihara, Kodai Saitoh, Kota Kagohashi, Yu ...
    2021 Volume 70 Issue 3 Pages 360-367
    Published: 2021
    Released: July 10, 2021
    JOURNAL FREE ACCESS

    Background: Propolis is a resinous mixture produced by honey bees that contains cinnamic acid derivatives and flavonoids. Although propolis has been reported to inhibit mast cell functions and mast cell-dependent allergic responses, the effect of propolis on basophil biology remains unknown. This study aimed to investigate the inhibitory effect of propolis on FcεRI-mediated basophil activation.

    Methods: To determine the inhibitory effect of propolis on basophil activation in vitro, cytokine production and FcεRI signal transduction were analyzed by ELISA and western blotting, respectively. To investigate the inhibitory effect of propolis in vivo, IgE-CAI and a food allergy mouse model were employed.

    Results: Propolis treatment resulted in the suppression of IgE/antigen-induced production of IL-4, IL-6 and IL-13 in basophils. Phosphorylation of FcεRI signaling molecules Lyn, Akt and ERK was inhibited in basophils treated with propolis. While propolis did not affect the basophil population in the treated mice, propolis did inhibit IgE-CAI. Finally, ovalbumin-induced intestinal anaphylaxis, which involves basophils and basophil-derived IL-4, was attenuated in mice prophylactically treated with propolis.

    Conclusions: Taken together, these results demonstrate the ability of propolis to suppress IgE-dependent basophil activation and basophil-dependent allergic inflammation. Therefore, prophylactic treatment with propolis may be useful for protection against food allergic reactions in sensitive individuals.

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