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11 pages, 1530 KiB

Open AccessArticle

Extracellular Vesicles Derived from Allergen Immunotherapy-Treated Mice Suppressed IL-5 Production from Group 2 Innate Lymphoid Cells

by Masaya Matsuda, Seito Shimizu, Kazuyuki Kitatani and Takeshi Nabe

Pathogens 2022, 11(11), 1373; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11111373 - 17 Nov 2022

Cited by 2 | Viewed by 1459

Abstract

Allergen immunotherapy (AIT), such as subcutaneous immunotherapy (SCIT), is a treatment targeting the causes of allergic diseases. The roles of extracellular vesicles (EVs), bilayer lipid membrane blebs released from all types of cells, in AIT have not been clarified. To examine the roles [...] Read more.

Allergen immunotherapy (AIT), such as subcutaneous immunotherapy (SCIT), is a treatment targeting the causes of allergic diseases. The roles of extracellular vesicles (EVs), bilayer lipid membrane blebs released from all types of cells, in AIT have not been clarified. To examine the roles of EVs in SCIT, it was analyzed whether (1) EVs are phenotypically changed by treatment with SCIT, and (2) EVs derived from SCIT treatment suppress the function of group 2 innate lymphoid cells (ILC2s), which are major cells contributing to type 2 allergic inflammation. As a result, (1) expression of CD9, a canonical EV marker, was highly up-regulated by SCIT in a murine model of asthma; and (2) IL-5 production from ILC2s in vitro was significantly decreased by the addition of serum EVs derived from SCIT-treated but not non-SCIT-treated mice. In conclusion, it was indicated that EVs were transformed by SCIT, changing to a suppressive phenotype of type 2 allergic inflammation. Full article

(This article belongs to the Special Issue Allergy and Immunotherapy)

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10 pages, 1726 KiB

Open AccessArticle

Suppressive Effect of Lactococcus lactis subsp. cremoris YRC3780 on a Murine Model of Japanese Cedar Pollinosis

by Kenji Uchida, Kenichi Iida, Ikumi Fujioka, Satoshi Hachimura and Osamu Kaminuma

Pathogens 2022, 11(11), 1347; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11111347 - 14 Nov 2022

Cited by 1 | Viewed by 1539

Abstract

Accumulating evidence suggests that Lactococcus lactis subsp. cremoris YRC3780 isolated from kefir has the potential to alleviate allergic responses. Herein, we investigated the effect of YRC3780 on a murine model of Japanese cedar pollinosis (JCP). BALB/c mice immunized with cedar pollen extract (CPE) [...] Read more.

Accumulating evidence suggests that Lactococcus lactis subsp. cremoris YRC3780 isolated from kefir has the potential to alleviate allergic responses. Herein, we investigated the effect of YRC3780 on a murine model of Japanese cedar pollinosis (JCP). BALB/c mice immunized with cedar pollen extract (CPE) exhibited an increase in serum immunoglobulin E and developed nasal inflammatory responses including sneezing, nasal hyperresponsiveness, and nasal eosinophil accumulation upon intranasal allergen challenge. These responses were suppressed by the oral administration of YRC3780, although the effects on CPE-induced sneezing response and eosinophil infiltration were not statistically significant. Total fecal microbiota diversity was not affected by allergen immunization and challenge or by YRC3780 administration. However, the abundances of Bifidobacteriales, Veillonellaceae, Lactococcus, and Lactococcus lactis were larger and that of Bacteroides was smaller in YRC3780-treated mice compared with those in CPE-challenged and YRC3780-untreated mice. Our findings suggest the usefulness of YRC3780 for alleviating JCP. Full article

(This article belongs to the Special Issue Allergy and Immunotherapy)

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12 pages, 1747 KiB

Open AccessArticle

Complement Factor H Is an Early Predictive Biomarker of the Therapeutic Efficacy of Sublingual Immunotherapy for Japanese Cedar Pollinosis

by Riyo Yoneda, Tomohisa Iinuma, Daiju Sakurai, Junya Kurita, Tomoyuki Arai, Yuri Sonobe, Syuji Yonekura, Yoshitaka Okamoto and Toyoyuki Hanazawa

Pathogens 2022, 11(11), 1280; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11111280 - 01 Nov 2022

Viewed by 985

Abstract

Sublingual immunotherapy for Japanese cedar pollinosis can improve the symptoms of allergic rhinitis and modify its natural course. However, sublingual immunotherapy requires a long treatment period and some patients do not respond to treatment. In this study, we aimed to identify biomarkers that [...] Read more.

Sublingual immunotherapy for Japanese cedar pollinosis can improve the symptoms of allergic rhinitis and modify its natural course. However, sublingual immunotherapy requires a long treatment period and some patients do not respond to treatment. In this study, we aimed to identify biomarkers that could predict the efficacy of sublingual immunotherapy at an early stage. In this study, 40 patients from phase III trials were recruited and divided into good and poor response groups. Using peripheral blood mononuclear cells from before and two months after the start of medication, microarray, discriminant analysis, and real-time polymerase chain reaction were performed to extract candidate genes that could be biomarkers. Furthermore, these genes were validated in 30 patients in general clinical practice. Complement factor H was upregulated in the good response group and downregulated in the poor response group. Complement factor H may be a useful biomarker for predicting the efficacy of sublingual immunotherapy for Japanese cedar pollinosis at early time points after treatment initiation. Full article

(This article belongs to the Special Issue Allergy and Immunotherapy)

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6 pages, 204 KiB

Open AccessArticle

Plant Food Allergy Improvement after Grass Pollen Sublingual Immunotherapy: A Case Series

by Fabiana Furci and Luisa Ricciardi

Pathogens 2021, 10(11), 1412; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10111412 - 30 Oct 2021

Cited by 5 | Viewed by 1603

Abstract

Background: Cross-reactivity between pollens and plant food has been widely described. Pollen extract subcutaneous immunotherapy in patients with pollens and plant food allergy has been shown to improve tolerance not only to inhalant allergens but also to reduce symptoms in patients with various [...] Read more.

Background: Cross-reactivity between pollens and plant food has been widely described. Pollen extract subcutaneous immunotherapy in patients with pollens and plant food allergy has been shown to improve tolerance not only to inhalant allergens but also to reduce symptoms in patients with various food allergies. Methods: We retrospectively report our experience with 15 female patients with a positive history for moderate, persistent allergic rhinitis due to grass pollen and oropharyngeal symptoms after ingestion of different plant food. These patients followed a five-grass pollen sublingual tablet immunotherapy for three years in a discontinuous pre-co-seasonal scheme. Results: All 15 patients treated with the 5-grass pollen sublingual tablet immunotherapy, taken once daily for 3 years on a 7-month course, showed improved ocular/nasal symptoms, with a reduction in the use of symptomatic drugs (e.g., nasal corticosteroids and H1 antihistamines). After the first seven-month course of immunotherapy, all patients declared a good tolerance to the intake of fruits and vegetables, and in particular, good tolerance to the offending foods. Conclusions: In conclusion, we have observed improvement of both respiratory and plant food allergies after sublingual immunotherapy (SLIT) with a five-grass pollen tablet. Full article

(This article belongs to the Special Issue Allergy and Immunotherapy)

Review

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9 pages, 765 KiB

Open AccessReview

Sublingual Immunotherapy for Japanese Cedar Pollinosis: Current Clinical and Research Status

by Daiju Sakurai, Hiroki Ishii, Ayumi Shimamura, Daisuke Watanabe, Takaaki Yonaga and Tomokazu Matsuoka

Pathogens 2022, 11(11), 1313; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11111313 - 09 Nov 2022

Cited by 2 | Viewed by 1840

Abstract

The incidence of Japanese cedar pollinosis is increasing significantly in Japan, and a recent survey suggested that about 40% of the population will develop this disease. However, spontaneous remission is rare. The increased incident rate of Japanese cedar pollinosis is a huge issue [...] Read more.

The incidence of Japanese cedar pollinosis is increasing significantly in Japan, and a recent survey suggested that about 40% of the population will develop this disease. However, spontaneous remission is rare. The increased incident rate of Japanese cedar pollinosis is a huge issue in Japan. Allergen immunotherapy is the only fundamental treatment that modifies the natural course of allergic rhinitis and provides long-term remission that cannot be induced by general drug therapy. Sublingual immunotherapy for Japanese cedar pollinosis has been developed and has been covered by health insurance since 2014 in Japan. The indication for children was expanded in 2018. Clinical trials of sublingual immunotherapy for Japanese cedar pollinosis have demonstrated its long-term efficacy and safety. It is recommended for patients who wish to undergo fundamental treatment regardless of the severity of the practical guidelines for the management of allergic rhinitis in Japan. For sublingual immunotherapy, a long-term treatment period of 3 years or longer is recommended to obtain stable therapeutic effects. In recent years, evidence based on basic research and clinical trials has demonstrated sublingual immunotherapy-induced immunological changes and efficacy in patients; however, biomarkers that objectively predict and judge these therapeutic effects need to be established. Full article

(This article belongs to the Special Issue Allergy and Immunotherapy)

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9 pages, 557 KiB

Open AccessReview

Diagnosis and Treatment of Local Allergic Rhinitis

by Tetsuya Terada and Ryo Kawata

Pathogens 2022, 11(1), 80; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens11010080 - 09 Jan 2022

Cited by 14 | Viewed by 5932

Abstract

Some patients with chronic rhinitis have a positive nasal allergen provocation test (NAPT) without systemic IgE sensitization by skin prick tests or serum allergen-specific IgE (sIgE). This novel concept is called local allergic rhinitis (LAR) and affects children and adults worldwide, but is [...] Read more.

Some patients with chronic rhinitis have a positive nasal allergen provocation test (NAPT) without systemic IgE sensitization by skin prick tests or serum allergen-specific IgE (sIgE). This novel concept is called local allergic rhinitis (LAR) and affects children and adults worldwide, but is underdiagnosed. LAR is not just the initial state of allergic rhinitis (AR), it is a unique form of chronic rhinitis that is neither classical AR nor non-AR. Many of the features of AR and LAR are similar, such as a positive NAPT, positive type 2 inflammatory markers, including the nasal discharge of sIgE, and a high incidence of asthma. A differential diagnosis of LAR needs to be considered in patients with symptoms suggestive of AR in the absence of systemic atopy, regardless of age. The diagnostic method for LAR relies on positive responses to single or multiple allergens in NAPT, the sensitivity, specificity, and reproducibility of which are high. The basophil activation test and measurement of IgE in nasal secretions also contribute to the diagnosis of LAR. Treatment for LAR is similar to that for AR and is supported by the efficacy and safety of allergen exposure avoidance, drug therapy, and allergen immunotherapy. This review discusses current knowledge on LAR. Full article

(This article belongs to the Special Issue Allergy and Immunotherapy)

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10 pages, 627 KiB

Open AccessReview

Allergen Immunotherapy in Asthma

by Kazuyuki Nakagome and Makoto Nagata

Pathogens 2021, 10(11), 1406; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10111406 - 29 Oct 2021

Cited by 10 | Viewed by 4014

Abstract

Allergen immunotherapy (AIT) is a specific treatment involving the administration of relevant allergens to allergic patients, with subtypes including subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). In asthma, AIT using the house dust mite (HDM) alleviates clinical symptoms and decreases airway hyper responsiveness [...] Read more.

Allergen immunotherapy (AIT) is a specific treatment involving the administration of relevant allergens to allergic patients, with subtypes including subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT). In asthma, AIT using the house dust mite (HDM) alleviates clinical symptoms and decreases airway hyper responsiveness and medication dose. In addition, AIT can improve the natural course of asthma. For example, the effects of AIT can be preserved for at least a few years, even after ending treatment. AIT may increase the remission rate of asthma in children and suppress sensitization to new allergens. If AIT is introduced in pollinosis, AIT may prevent the development of asthma. Moreover, AIT can control other allergic diseases complicated by asthma, such as allergic rhinitis, which also improves the control of asthma. The indication of HDM-SCIT for asthma is mild-to-moderate HDM-sensitized allergic asthma in a patient with normal respiratory function. To date, HDM-SLIT is applicable in Japan for allergic rhinitis, not for asthma. However, the effect of SLIT on asthma has been confirmed internationally, and SLIT is available for asthma in Japan if allergic rhinitis is present as a complication. Full article

(This article belongs to the Special Issue Allergy and Immunotherapy)

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7 pages, 660 KiB

Open AccessReview

Relationship between Saliva and Sublingual Immunotherapy

by Aiko Oka and Mitsuhiro Okano

Pathogens 2021, 10(11), 1358; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10111358 - 21 Oct 2021

Cited by 2 | Viewed by 2239

Abstract

The demand for allergen specific immunotherapy (AIT), especially sublingual immunotherapy (SLIT), is increasing because of its efficacy in inducing clinical remission of allergic diseases and its low risk of side effects. Since not all patients that undergo SLIT demonstrate an improvement in allergic [...] Read more.

The demand for allergen specific immunotherapy (AIT), especially sublingual immunotherapy (SLIT), is increasing because of its efficacy in inducing clinical remission of allergic diseases and its low risk of side effects. Since not all patients that undergo SLIT demonstrate an improvement in allergic symptoms, the development of biomarkers to predict the outcome and adjuvants for SLIT is desired. Saliva is the first target with which tablets used in SLIT come into contact, and salivary pH, chemical properties or microbiome composition are reported to possibly be associated with the outcome of SLIT. Antibodies such as IgG4 and IgA not only in the serum but also in the saliva are increased after SLIT and may also be associated with the efficacy of SLIT. The development of the metagenomic sequencing technique makes it possible to determine the microbiome composition and ratio of each bacterium, and researchers can investigate the relationships between specific bacteria and the immune response. Some bacteria are reported to improve the SLIT outcome and have the potential to be used as biomarkers for the selection of patients and as adjuvants in SLIT. Here, we introduce biomarkers for SLIT and present recent findings regarding the relationship between saliva and SLIT. Full article

(This article belongs to the Special Issue Allergy and Immunotherapy)

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17 pages, 792 KiB

Open AccessReview

Oral Immunotherapy for Children with Cow’s Milk Allergy

by Mika Ogata, Jun Kido and Kimitoshi Nakamura

Pathogens 2021, 10(10), 1328; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10101328 - 15 Oct 2021

Cited by 7 | Viewed by 3209

Abstract

Cow’s milk allergy (CMA) is one of the most common IgE-dependent food allergies in children. Some children develop severe and persistent CMA, with near-fatal reactions after exposure to trace amounts of cow’s milk (CM). Because milk and dairy products are included in various [...] Read more.

Cow’s milk allergy (CMA) is one of the most common IgE-dependent food allergies in children. Some children develop severe and persistent CMA, with near-fatal reactions after exposure to trace amounts of cow’s milk (CM). Because milk and dairy products are included in various processed food products, it is difficult to completely remove milk, which negatively affects the quality of life of children with CMA. Oral immunotherapy (OIT) can alleviate food allergen-induced anaphylaxis under continuous ingestion of a little of the causative food. Children with severe CMA may benefit from OIT, but the treatment requires a long time and poses a risk of anaphylaxis. Moreover, in recent years, new therapies, including omalizumab, sublingual immunotherapy, and epicutaneous immunotherapy, have played the role of optional OIT. In this review, we present the current methods of and other attempts at OIT, and discuss OIT for safely treating CMA. Full article

(This article belongs to the Special Issue Allergy and Immunotherapy)

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11 pages, 1200 KiB

Open AccessReview

Sublingual Immunotherapy: How Sublingual Allergen Administration Heals Allergic Diseases; Current Perspective about the Mode of Action

by Minoru Gotoh and Osamu Kaminuma

Pathogens 2021, 10(2), 147; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10020147 - 02 Feb 2021

Cited by 3 | Viewed by 2663

Abstract

Owing to the successful application of sublingual immunotherapy (SLIT), allergen immunotherapy (AIT) has become one of the leading treatments for allergic diseases. Similar to the case with other AITs, such as subcutaneous and oral immunotherapies, not only the alleviation of allergic symptoms, but [...] Read more.

Owing to the successful application of sublingual immunotherapy (SLIT), allergen immunotherapy (AIT) has become one of the leading treatments for allergic diseases. Similar to the case with other AITs, such as subcutaneous and oral immunotherapies, not only the alleviation of allergic symptoms, but also the curing of the diseases can be expected in patients undergoing SLIT. However, how and why such strong efficacy is obtained by SLIT, in which allergens are simply administered under the tongue, is not clearly known. Various potential mechanisms, including the induction of blocking antibodies, T cell tolerance, regulatory B and T cells, CD103^-CD11b⁺ classical dendritic cells, and CD206⁺ macrophages, and the reduction of innate lymphoid cells, mast cells, and basophils, have been suggested. Recently, through a comparative analysis between high- and non-responder patients of SLIT, we have successfully proposed several novel mechanisms. Here, we introduce our recent findings and summarize the current understanding of the mechanisms underlying the strong efficacy of SLIT. Full article

(This article belongs to the Special Issue Allergy and Immunotherapy)

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