Establishment of autoimmune primary aldosteronism and development of autoantibody assay

• Project/Area Number: 17K09877
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Kanazawa University
• Principal Investigator: DEMURA MASASHI 金沢大学, 医学系, 准教授 (00507080)
• Co-Investigator(Kenkyū-buntansha): 西條 清史 金沢大学, 医学系, 教授 (00178469)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 原発性アルドステロン症 / 自己抗体 / 自己免疫疾患

Outline of Final Research Achievements

Primary aldosteronism (PA) is a common disease, with an estimated 2-4 million domestic patients (1-2% of the total population, 10-20% of hypertensive patients). Although 60-80% of PA patients have been found to be bilateral hypersecretion, there are many unclear causes of bilateral hypersecretion, and few patients can identify the cause. Considering the mechanism of autoantibody as a cause, we found a case with aldosterone-stimulating IgG in the serum of bilateral PA. Furthermore, 15 types of proteins (self-antigen candidates) recognized by these IgGs were identified. In the future, it is expected that a new pathological condition of autoimmune primary aldosteronism and the establishment of an antibody measurement method will be established by further reinforcing the data.

Academic Significance and Societal Importance of the Research Achievements

両側性原発性アルドステロン症の原因として、自己抗体によるアルドステロン分泌過剰症の存在が示唆される。これまで原因不明とされてきた多くの両側性原発性アルドステロン症の病態解明つながる成果と考えられる。
社会的意義としては、①不要な検査の回避：PA診断に必要な機能確認検査（薬剤などの負荷）や副腎静脈サンプリングを回避できる。②正確な診断できる。③簡便・簡単・低侵襲：末梢静脈採血のみで診断できる。④すべての施設で実施可能：AVS実施可能施設は極めて限定されるのに対し、採血はすべての医療機関で実施可能である。④安価：抗体検査は、機能確認検査や副腎静脈サンプリングより安価である。

Research Products

• [Journal Article] Genetic and epigenetic analyses of aldosterone-producing adenoma with hypercortisolemia (2019)
  • Author(s): Kometani Mitsuhiro, Yoneda Takashi, Demura Masashi, Aono Daisuke, Gondoh Yuko, Karashima Shigehiro, Nishimoto Koshiro, Yasuda Masanori, Horike Shin-ichi, Takeda Yoshiyu
  • Journal Title: Steroids Volume: 151 Pages: 108470-108470
  • DOI: 10.1016/j.steroids.2019.108470
  • Peer Reviewed / Open Access
• [Journal Article] Primary Aldosteronism Subtype Discordance Between Computed Tomography and Adrenal Venous Sampling (2019)
  • Author(s): Aono D, Kometani M, Karashima S, Usukura M, Gondo Y, Hashimoto A, Demura M, Furukawa K, Takeda Y, Kawashiri M, Yoneda T.
  • Journal Title: Hypertens Res Volume: 42 Issue: 12 Pages: 1942-1950
  • DOI: 10.1038/s41440-019-0310-y
  • Peer Reviewed
• [Journal Article] Epigenetic Regulation of Aldosterone Synthase Gene by Sodium and Angiotensin II. (2018)
  • Author(s): Takeda Y, Demura M, Wang F, Karashima S, Yoneda T, Kometani M, Hashimoto A, Aono D, Horike SI, Meguro-Horike M, Yamagishi M, Takeda Y.
  • Journal Title: J Am Heart Assoc. Volume: 7 Issue: 10
  • DOI: 10.1161/jaha.117.008281
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impact of aldosterone-producing cell clusters on diagnostic discrepancies in primary aldosteronism (2018)
  • Author(s): Kometani Mitsuhiro、Yoneda Takashi、Aono Daisuke、Karashima Shigehiro、Demura Masashi、Nishimoto Koshiro、Yamagishi Masakazu、Takeda Yoshiyu
  • Journal Title: Oncotarget Volume: 9 Issue: 40 Pages: 26007-26018
  • DOI: 10.18632/oncotarget.25418
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effect of sodium glucose cotransporter 2 inhibitors on obstructive sleep apnea in patients with type 2 diabetes (2018)
  • Author(s): Sawada Kei、Karashima Shigehiro、Kometani Mitsuhiro、Oka Rie、Takeda Yoshimichi、Sawamura Toshitaka、Fujimoto Aya、Demura Masashi、Wakayama Ayako、Usukura Mikiya、Yagi Kunimasa、Takeda Yoshiyu、Yoneda Takashi
  • Journal Title: Endocrine Journal Volume: 65 Issue: 4 Pages: 461-467
  • DOI: 10.1507/endocrj.EJ17-0440
  • NAID: 130006727071
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Severe Mitral Regurgitation As a Result of Rupture of Mitral Valve Chordae Tendineae in a Patient With Graves Disease. (2018)
  • Author(s): Karashima S, Tsuda T, Kometani M, Oka R, Demura M, Kawashiri MA, Takeda Y, Hayashi K, Yoneda T.
  • Journal Title: J Endocr Soc. Volume: 2 Issue: 11 Pages: 1246-1250
  • DOI: 10.1210/js.2018-00173
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Patent(Industrial Property Rights)] 原発性アルドステロン症の検査方法 (2018)
  • Inventor(s): 出村 昌史
  • Industrial Property Rights Holder: 国立大学法人金沢大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018