2022 Fiscal Year Final Research Report

Elucidation of the IgE class switch mechanism involved in localized allergic rhinitis and its therapeutic implications

Research Project

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Project/Area Number	19K08879
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 54020:Connective tissue disease and allergy-related
Research Institution	Saitama Medical University (2020-2022) University of Toyama (2019)
Principal Investigator	Itazawa Toshiko 埼玉医科大学, 医学部, 准教授 (70361970)
Co-Investigator(Kenkyū-buntansha)	足立雄一富山大学, 学術研究部医学系, 教授 (80184191)
Project Period (FY)	2019-04-01 – 2023-03-31
Keywords	局所性アレルギー性鼻炎 / アレルギー性鼻炎 / IgE / クラススイッチ / BAFF / IL-25
Outline of Final Research Achievements	There are two types of allergic rhinitis (AR), namely, atopic AR and localized allergic rhinitis (LAR). In LAR, antigen-specific IgE is only detected in the nasal mucosa and not in the blood. However, the pathogenesis of LAR remains unclear. In this study, to elucidate the mechanism by which IgE is produced only in the nasal mucosa, we established a culture system in which IgE production was induced by antigen stimulation using human naive B cells, but we were unable to evaluate class switching recombination (CSR) to IgE at the gene level. In patients with atopic AR, the levels of B-cell activating factor (BAFF), which are involved in CSR, and IL-25, an epithelium-derived cytokine, in nasal secretions were associated with the severity of rhinitis. However, the levels of BAFF and IL-25 in the nasal secretions of patients with LAR remain unknown.
Free Research Field	アレルギー
Academic Significance and Societal Importance of the Research Achievements	近年、LARという新しい概念が注目されているが、病態は不明な点が多い。鼻粘膜局所でのみ抗原特異的IgEが産生されるLARの発症機序を解明するために、抗原刺激によりIgEへのCSRが誘導されるヒトB細胞を用いた培養系の確立が必要である。また、鼻汁中のIgEおよびIgE産生に関与する蛋白やサイトカインの評価は、LARを含めたARの病態解明につながり、診断、重症度、治療効果判定などのバイオマーカーとなる可能性がある。LARの診断としては、鼻粘膜局所における抗原特異的IgEの証明や鼻誘発試験が陽性であることを確認する必要があるが、日常診療では容易ではないため、今後は簡便な診断方法の確立が課題である。