Antigen epitopes of serum anti-Helicobacter pylori antibody along H. pylori infection to gastric cancer onset

• Project/Area Number: 17K09353
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Oita University
• Principal Investigator: Akada Junko 大分大学, 医学部, 助教 (30346548)
• Co-Investigator(Kenkyū-buntansha): 村上 和成 大分大学, 医学部, 教授 (00239485) ; 山岡 吉生 大分大学, 医学部, 教授 (00544248)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2019: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ヘリコバクター・ピロリ / 血清 / 抗体 / 胃癌 / アジア / 既感染 / 血清抗体 / CagA / 抗原エピトープ / ペプチド / エピトープ

Outline of Final Research Achievements

Helicobacter pylori induce gastric cancer after life-long chronic infection. To promote gastric cancer prevention, it is necessary to find gastric cancer patients in very early stage, or high-risk persons of gastric cancer before onset, at the occasion of population-based mass-screening of gastric cancer. Using non-invasive serum samples, we evaluated regional characters and disease-related characters of anti-H. pylori and anti-CagA antibodies. We identified two of major antigenic epitopes of anti-CagA antibody using comprehensive CagA antigen epitope peptide ELISA array. We could not analyze transition of antigen epitopes variations along the process of gastric cancer onset.

Academic Significance and Societal Importance of the Research Achievements

ピロリ菌抗体情報量を飛躍的に広げ、ピロリ菌感染症抗体変遷の全体像が掌握し、ピロリ菌抗体検査で問題となっている陰性高値検体の科学的実態を明確にできれば、ピロリ菌抗体検査の改良点を見出せるのではないかと考えるが、そこまで到達することができなかった。学術的には抗体の背景にあるエピトープ特異的免疫反応の研究へと進む必要がある。血清抗体を手掛かりに、ピロリ菌慢性感染症においていかに炎症発癌が誘導されるのか、研究の進展を期待する。

Research Products

• [Int'l Joint Research] Cho Ray Hospital, Ho Chi Minh City/108 Military Central Hospital, Hanoi(ベトナム)
• [Int'l Joint Research] Airlangga University, Surabaya/University of Indonesia, Jakarta(インドネシア)
• [Int'l Joint Research] J.D.Wangchuck National Referral Hospital(ブータン)
• [Int'l Joint Research] Tribhuvan University Teaching Hospital,(ネパール)
• [Int'l Joint Research] No (1) Defense Service General Hospital/No (2) Defense Service General Hospital(ミャンマー)
• [Int'l Joint Research]
• [Int'l Joint Research] Cho Ray Hospital, Ho Chi Minh/108 Military Central Hospital, Hanoi(ベトナム)
• [Int'l Joint Research] Universitas Airlangga, Surabaya/University of Indonesia, Jakarta(インドネシア)
• [Int'l Joint Research] National Referral Hospital(ブータン)
• [Int'l Joint Research] No (2) Defense Service General Hospital/No (1) Defense Service General Hospital(ミャンマー)
• [Int'l Joint Research] Dhaka Medical Collage and Hospital(バングラデシュ)
• [Int'l Joint Research]
• [Int'l Joint Research] Cho Ray Hospital/108 Military Central Hospital(ベトナム)
• [Journal Article] Serum Helicobacter pylori antibody reactivity in seven Asian countries using an automated latex aggregation turbidity assay (2021)
  • Author(s): Akada J,Tshibangu‐K,Tuan V,Kurogi S,Matsuo Y,Ansari S,Doohan D,Phuc B,Subsomwong P,Waskito L,Binh T,Nguyen L,Khien V,Dung H,Miftahussurur M,Syam A,Tshering L,Vilaichone R,Mahachai V,Ratanachu‐ek T,Shrestha P,Yee T,Htet K,Aftab H,Matsuhisa T,Uchida T,Okimoto T,Mizukami K,Kodama M,Murakami K,Takahashi N,Yamaoka Yoshio
  • Journal Title: Journal of Gastroenterology and Hepatology Volume: - Issue: 8 Pages: 1-10
  • DOI: 10.1111/jgh.15467
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Characterization of a novel Helicobacter pylori East Asian-type CagA ELISA for detecting patients infected with various cagA genotypes (2020)
  • Author(s): Doohan D, Miftahussurur M, Matsuo Y, Kido Y, Akada J, Matsuhisa T, Yee TT, Htet K, Aftab H, Vilaichone RK, Mahachai V, Ratanachu-Ek T, Tshering L, Waskito LA, Fauzia KA, Uchida T, Syam AF, Rezkitha YAA, Yamaoka Y
  • Journal Title: Medcal Microbiology and Immunology Volume: 209 Issue: 1 Pages: 29-40
  • DOI: 10.1007/s00430-019-00634-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Epitope peptides of Helicobacter pylori CagA antibodies from sera by whole-peptide mapping (2019)
  • Author(s): Shamshul Ansari ; Junko Akada; Yuichi Matsuo; Seiji Shiota; Yoko Kudo; Tadayoshi Okimoto; Kazunari Murakami; Yoshio Yamaoka
  • Journal Title: J Gastroenterology Volume: 54 Issue: 12 Pages: 1039-1051
  • DOI: 10.1007/s00535-019-01584-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Novel CagA ELISA exhibits enhanced sensitivity of Helicobacter pylori CagA antibody. (2017)
  • Author(s): Matsuo Y, Kido Y, Akada J, Shiota S, Binh TT, Trang TT, Dung HD, Tung PH, Tri TD, Thuan NP, Tam LQ, Nam BC, Khien VV, Yamaoka Y.
  • Journal Title: World J Gastroenterol Volume: 23(1) Issue: 1 Pages: 48-59
  • DOI: 10.3748/wjg.v23.i1.48
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Performance of novel Helicobacter pylori East Asian-type CagA ELISA for detecting patients infected with various cagA genotypes (2019)
  • Author(s): Dalla Doohan, Muhammad Miftahussurur, Yuichi Matsuo, Yasutoshi Kido, Junko Akada, Langgeng Agung Waskito, Kartika Afrida Fauzia, Tomohisa Uchida, Takashi Matsumoto, Yoshio Yamaoka
  • Organizer: 第72回 日本細菌学会九州支部総会・第56回日本ウイルス学会九州支部総会
• [Presentation] Helicobacter pylori CagA-peptide epitopes capable to detect antibodies in Japanese patients’ sera (2019)
  • Author(s): Shamshul Ansari, Junko Akada, Seiji Shiota, Tadayoshi Okimoto, Kazunari Murakami, Yoshio Yamaoka
  • Organizer: 第92回日本細菌学会
• [Presentation] Helicobacter pylori CagA-peptide epitopes capable of detecting antibodies in Japanese patients’ sera (2018)
  • Author(s): Shamshul Ansari, Junko Akada, Seiji Shiota, Tadayoshi Okimoto, Kazunari Murakami, Yoshio Yamaoka
  • Organizer: 第24回日本ヘリコバクター学会学術集会共同開催 第15回韓日シンポジウム
• [Presentation] ラテックス凝集免疫比濁法によるアジア7か国のH. pylori血清抗体価の比較解析 (2018)
  • Author(s): 赤田 純子、Tshibangu Evariste Kabamba, 内田 智久、沖本 忠義、水上 一弘、兒玉 雅明、村上 和成、山岡 吉生
  • Organizer: 第24回日本ヘリコバクター学会学術集会
• [Presentation] Helicobacter pylori 病原因子CagAに対する血清抗体の 抗原エピトープ解析 (2018)
  • Author(s): Shamshul Ansari、赤田 純子、塩田 星児、 沖本 忠義、村上 和成、山岡 吉生
  • Organizer: 第71回日本細菌学会九州支部総会・第55回日本ウイルス学会九州支部総会
• [Patent(Industrial Property Rights)] ペプチド及びその利用 (2021)
  • Inventor(s): 赤田純子・山岡吉生・村上和成・塩田星児
  • Industrial Property Rights Holder: 大分大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2021
• [Patent(Industrial Property Rights)] ペプチド及びその利用 (2018)
  • Inventor(s): 赤田純子、山岡吉生、村上和成、塩田星児
  • Industrial Property Rights Holder: 大分大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2018-123612
  • Filing Date: 2018