Expression of estrogen receptors in tonsillar tissues of IgA nephropathy

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08736
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Yamagata University
• Principal Investigator: Yamakawa Mitsunori 山形大学, 医学部, 教授 (20183676)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: IgA腎症 / 口蓋扁桃 / リンパ上皮共生域 / 濾胞樹状細胞 / エストロゲン・レセプター / 胸腺間質リンホポイエチン

Outline of Final Research Achievements

The present study has firstly demonstrated the expression of estrogen receptor (ER)-alpha on squamous epithelial cells in lymphoepithelial symbiosis areas (LSAs), the specific squamous epithelial layer containing lymphocytes, and follicular dendritic cells in follicular germinal centers of palatine tonsils. Furthermore, tonsillar LSAs in patients with IgA nephropathy, in which renal glomerular deposition of aberrantly glycosylated IgA and immune complex containing glycosylated IgA is found related to mucosal and tonsillar infection, more frequently expressed the ER-alpha, compared to those with non-IgA nephropathy. In addition, there was a well correlation between the expression of ER-alpha and thymic stromal lymphopoietin in the tonsillar LSAs, the latter being a positive regulator for IgA production in the follicular germinal centers in the palatine tonsils.

Free Research Field

病理学

Academic Significance and Societal Importance of the Research Achievements

IgA腎症は慢性糸球体腎炎の主要な疾患で、治療法にはステロイドパルス療法、免疫抑制薬、口蓋扁桃摘出術（+ステロイドパルス併用療法）などの対象療法があるが、確立された有効な治療法はなく、透析や移植が必要な末期腎不全に至りやすい（成人発症例では20年間で約40%弱）。今回の研究で、扁桃のLSAの扁平上皮におけるER-alphaの発現が有意に高頻度で、IgA産生に関与するTSLPの発現と相関性が認められたことにより、難治性で予後不良な疾患であるIgA腎症に対して、TSLPやER-alphaに対する分子標的薬あるいは乳癌や子宮内膜癌などと同じような抗ホルモン療法が適応できうる可能性が示唆される。