Treatment duration-dependent efficacy of Japanese cedar pollen sublingual immunotherapy: Evaluation of a phase II/III trial over three pollen dispersal seasons

Yonekura, Syuji; Gotoh, Minoru; Kaneko, Shinya; Kanazawa, Keishi; Takeuji, Yoshie; Okubo, Kimihiro; Okamoto, Yoshitaka

doi:10.1016/j.alit.2019.05.002

Cited by 26 publications

(22 citation statements)

References 26 publications

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“…Recently, a higher dose SLIT tablet (5000 JAU) has become available and may be more effective than the lower dosage of 2000 JAU. 10,11 In our current study, we compared metachromatic cell, eosinophil and neutrophil numbers in nasal swabs of SLIT subjects and untreated subjects in preseason and in season. There were significant differences in total Mc number between SLIT patients and untreated patients in preseason (P = .014) and in season (P = .00001).…”

Section: Discussionmentioning

confidence: 99%

“…The symptom severity in SLIT subjects in preseason and in season was reduced compared to in untreated subjects. Recently, a higher dose SLIT tablet (5000 JAU) has become available and may be more effective than the lower dosage of 2000 JAU 10,11 …”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6][7][8][9] Recently, a SLIT tablet for JCP has been used to establish efficacy in a double blind, placebo controlled study and is increasingly widely used. 10,11 Various mechanisms have been proposed to explain the effectiveness of SLIT. In local targeted mucosae, transforming growth factor β (TGF-β) and Foxp3(+) were induced by interleukin 10 (IL10), and immunoglobulin G1 (IgG1) and IgG4 antibodies to pollen antigen produced by SLIT.…”

Section: Introductionmentioning

confidence: 99%

“…In other double blind, placebo controlled studies, SLIT has been shown to be effective in seasonal allergic rhinitis to grass, ragweed, birch, and tree pollen by using standardized liquid or tablet 4‐9 . Recently, a SLIT tablet for JCP has been used to establish efficacy in a double blind, placebo controlled study and is increasingly widely used 10,11 …”

Section: Introductionmentioning

confidence: 99%

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Decreased numbers of metachromatic cells in nasal swabs in Japanese cedar pollinosis following sublingual immunotherapy

Otsuka

Matsune

et al. 2020

Immunity Inflam & Disease

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Background and Objective: Nasal symptoms were reduced following allergenspecific sublingual immunotherapy (SLIT) for allergic rhinitis. The mechanisms underlying the effectiveness of SLIT for Japanese cedar pollinosis are poorly understood. We studied changes in the numbers of metachromatic cells, eosinophils, and neutrophils following SLIT for Japanese cedar pollinosis. Methods: Nasal swabs were taken in the preseason (n = 32) and in pollinosis season (n = 49) from subjects given sublingual drop immunotherapy for an average duration of 1.5 years. The numbers of metachromatic cells (mast cells and basophils), eosinophils and neutrophils were determined and compared with those from untreated subjects in preseason (n = 65) and in season (n = 54). Results: SLIT subjects had a significantly reduced frequency of moderate to most severe symptoms in comparison to untreated subjects in preseason (P < .001, the Mann-Whitney U test), and (P < .00001) in season. Metachromatic cell counts in nasal swabs of SLIT subjects in preseason and in season were lower than those of untreated subjects (P = .014, the Mann-Whitney U test) and (P = .00001) respectively. Eosinophil numbers in SLIT subjects were not significantly different than in untreated subjects in both preseason (P = .29) and in season (P = .09). However, when SLIT subjects in season were divided into those with greater than or equal to 1.5 years, or <1.5 years of SLIT duration, the degree of eosinophilia in those with SLIT greater than or equal to 1.5 years was significantly lower (P = .011) than in untreated patients, but not in those with SLIT less than 1.5 years (P = .9). There were no significant differences in neutrophil numbers in nasal swabs between untreated and SLIT subjects in preseason and in season. Conclusion: One of mechanisms underlying the effectiveness of sublingual drop immunotherapy for Japanese cedar pollinosis is a reduction of the number

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Decreased numbers of metachromatic cells in nasal swabs in Japanese cedar pollinosis following sublingual immunotherapy

Otsuka

Matsune

et al. 2020

Immunity Inflam & Disease

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“…Although this dose has been reported to be effective in improvement of clinical symptoms for both children and adults, a higher dose is desired to enhance efficacy, because it has been shown to be dose- and duration-dependent. 22 , 23 To improve clinical efficacy and patient convenience, JC-pollen SLIT tablets 5,000 JAU/day was selected as the optimum dose and is used for treatment during the maintenance phase. 23 However, the immunological effects of SLIT are lower than those of SLIT, since higher doses of the causative allergen (20- to 30-fold) are required for SLIT to obtain the same therapeutic effect as SCIT.…”

Section: Administration Routes Of Allergens For Aitmentioning

confidence: 99%

Next-Generation Allergen-Specific Immunotherapy for Japanese Cedar Pollinosis Using Molecular Approaches

Takaiwa¹

2021

ITT

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Japanese cedar (JC) pollinosis is the most major IgE-mediated type I allergic disease in Japan. Allergen-specific immunotherapy is the only curative treatment for allergic diseases. Subcutaneous immunotherapy and sublingual immunotherapy have been introduced in Japan for JC pollinosis, but do not avoid some adverse side effects, because the natural allergens used as tolerogens cross-link with specific IgE types on mast cells and basophils. To make immunotherapy for JC pollinosis safer, more effective and convenient, rice-based oral allergy vaccines using hybrid peptides composed of multiple T-cell epitopes or recombinant deconstructed hypoallergenic derivatives derived from major allergens — Cry j 1 and Cry j 2 — have been developed and their efficacy and safety evaluated by oral administration of transgenic rice seeds. Furthermore, recombinant modified JC allergens conjugated with various immunomodulatory molecules and DNA-based vaccines have been created and their efficacy assessed.

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Increased Thrombin‐Activatable Fibrinolysis Inhibitor in Response to Sublingual Immunotherapy for Allergic Rhinitis

et al. 2021

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Objectives/Hypothesis: The objective of this study was to determine the role of thrombin-activatable fibrinolysis inhibitor (TAFI) as a candidate biomarker for therapeutic efficacy of sublingual immunotherapy (SLIT) and to identify the role of TAFI in the pathogenesis of allergic rhinitis (AR).Study Design: Retrospective cohort study and laboratory study. Methods: Serum was collected from patients with allergies to Japanese cedar pollen before, during, and after treatment with SLIT. We measured the levels of immunoreactive TAFI, C3a, and C5a in serum by enzyme-linked immunosorbent assay (ELISA) and assessed their relative impact on a combined symptom-medication score. We also examined the impact of TAFI on mast cells and fibroblasts in experiments performed in vitro.Results: Serum levels of TAFI increased significantly in response to SLIT. By contrast, serum C3a levels decreased significantly over time; we observed a significant negative correlation between serum levels of TAFI versus C3a and symptommedication score. Mast cell degranulation was inhibited in response to TAFI, as it was the expression of both CCL11 and CCL5 in cultured fibroblasts.Conclusions: High serum levels of TAFI may be induced by SLIT. TAFI may play a critical protective role in pathogenesis of AR by inactivating C3a and by inhibiting mast cell degranulation and chemokines expression in fibroblasts.

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Treatment duration-dependent efficacy of Japanese cedar pollen sublingual immunotherapy: Evaluation of a phase II/III trial over three pollen dispersal seasons

Cited by 26 publications

References 26 publications

Decreased numbers of metachromatic cells in nasal swabs in Japanese cedar pollinosis following sublingual immunotherapy

Decreased numbers of metachromatic cells in nasal swabs in Japanese cedar pollinosis following sublingual immunotherapy

Next-Generation Allergen-Specific Immunotherapy for Japanese Cedar Pollinosis Using Molecular Approaches

Increased Thrombin‐Activatable Fibrinolysis Inhibitor in Response to Sublingual Immunotherapy for Allergic Rhinitis

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