Evaluation of Helicobacter hepaticus infection in children with liver disorders and postoperative biliary atresia

• Project/Area Number: 25461635
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Hyogo Medical University
• Principal Investigator: Okuda Masumi 兵庫医科大学, 医学部, 教授 (40531091)
• Co-Investigator(Kenkyū-buntansha): KAMIYA Shigeru 杏林大学, 医学部, 教授 (10177587) ; KIKUCHI Shogo 愛知医科大学, 医学部, 教授 (40224901) ; FUKUDA Yoshihiro 兵庫医科大学, 医学部, 名誉教授 (60148640) ; OSAKI Takako 杏林大学, 医学部, 准教授 (90255406) ; KONDOU Hiroki 大阪大学, 医学(系)研究科(研究院), 研究員 (10373515) ; 佐竹 真 兵庫医科大学, 医学部, 助教 (70399153) ; 前川 講平 兵庫医科大学, 医学部, 講師 (80412005)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: ヘリコバクター・ヘパティカス / 小児 / 肝障害 / イムノブロット / 抗体測定 / 血清抗体 / ペプチド / ELISA法 / Helicobacter hepaticus / プロテオーム解析 / 胆道閉鎖症 / 肝機能障害

Outline of Final Research Achievements

Helicobacter hepaticus (H. hepaticus) is a gram-negative, spiral shaped microaerophilic bacterium. Several studies have suggested the possibility that infection of this bacterium plays a role in the pathogenesis of liver diseases in humans. We evaluated the association between H. hepaticus and children with liver disorders. Furthermore, we detect the antigenic H. hepaticus protein recognized by child sera using 2-DE immunoblot analysis. Positive rate of H. hepaticus in children without and with liver disorders was 30.3% (10/33) and 44.4% (4/9), respectively. Total 25 proteins were identified as candidate antigens by LS-MS/MS after the 2-DE immunoblot analysis. Among the proteins, flagelin A was the most reactive protein, particularly against highly reactive sera, although low reactive sera also detected the spot slightly.

Research Products

• [Journal Article] Low Prevalence and Incidence of Helicobacter pylori Infection in Children: A Population-Based Study in Japan. (2015)
  • Author(s): Okuda M, Osaki T, Lin Y, Yonezawa H, Maekawa K, Kamiya S, Fukuda Y, Kikuchi S.
  • Journal Title: Helicobacter Volume: 20 Issue: 2 Pages: 133-138
  • DOI: 10.1111/hel.12184
  • Peer Reviewed / Open Access
• [Journal Article] Proteomic Characterization of Helicobacter pylori CagA Antigen Recognized by Child Serum Antibodies and Its Epitope Mapping by Peptide Array (2014)
  • Author(s): Junko Akada , Masumi Okuda, Narumi Hiramoto, Takao Kitagawa, Xiulian Zhang, Shuichi Kamei, Akane Ito, Mikiko Nakamura, Tomohisa Uchida, Tomoko Hiwatani, Yoshihiro Fukuda, Teruko Nakazawa, Yasuhiro Kuramitsu, Kazuyuki Nakamura
  • Journal Title: PLOS ONE Volume: 9 Issue: 8 Pages: e104611-e104611
  • DOI: 10.1371/journal.pone.0104611
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Evaluation of a stool antigen test using a monoclonal antibody for native catalase for diagnosis of Helicobacter pylori infection in children and adults. (2014)
  • Author(s): Okuda M, Osaki T, Kikuchi S, Ueda J, Lin Y, Yonezawa H, Maekawa K, Hojo F, Kamiya S, Fukuda Y.
  • Journal Title: J Med Microbiol. Volume: 63 Issue: 12 Pages: 1621-1625
  • DOI: 10.1099/jmm.0.077370-0
  • Peer Reviewed / Open Access
• [Journal Article] Diagnostic Accuracy of the E-Plate Serum Antibody Test Kit in Detecting <i>Helicobacter pylori</i> Infection Among Japanese Children (2014)
  • Author(s): Ueda J, Okuda M, Nishiyama T, Lin Y, Fukuda Y, Kikuchi S
  • Journal Title: Journal of Epidemiology Volume: 24 Issue: 1 Pages: 47-51
  • DOI: 10.2188/jea.JE20130078
  • NAID: 130003383378
  • ISSN: 0917-5040, 1349-9092
  • Peer Reviewed
• [Journal Article] Diagnostic accuracy of urine-based kits for detection of Helicobacter pylori antibody in children (2013)
  • Author(s): Okuda M
  • Journal Title: Pediatr Int Volume: 印刷中 Issue: 3 Pages: 337-341
  • DOI: 10.1111/ped.12057
  • Peer Reviewed
• [Journal Article] A new infant case of Nakajo-Nishimura syndrome with a genetic mutation in the immunoproteasome subunit (2013)
  • Author(s): Kunimoto K, Kimura A, Uede K, Aoyagi N, Furukawa F, Kanazawa N
  • Journal Title: Dermatology Volume: 227 Issue: 1 Pages: 26-30
  • DOI: 10.1159/000351323
  • Peer Reviewed
• [Presentation] Detection of antigenic Helicobacter hepaticus protein recognized by child serum antibodies (2015)
  • Author(s): Okuda M, Akada J, Osaki T, Kitagawa T, Kuramitsu Y, Kamiya S, Fukuda Y
  • Organizer: CHRO Conference 2015
  • Place of Presentation: ニュージーランド、ロトルア
  • Year and Date: 2015-11-02
  • Int'l Joint Research
• [Presentation] Helicobacter pylori CagA as a dominant antigen recognized by Japanese child serum antibodies (2015)
  • Author(s): Okuda M, Akada J, Fukuda Y.
  • Organizer: The 12th Japan-Korea Joint Symposium on Helicobacter Infection
  • Place of Presentation: Jeju, Korea
  • Year and Date: 2015-03-20 – 2015-03-21
• [Presentation] Helicobacter pylori CagA as a dominant antigen recognized by Japanese child serum antibodies (2014)
  • Author(s): Okuda M, Akada J, Nakamura K, Nakazawa T, Fukuda Y.
  • Organizer: European Helicobacter Study Group XXVIIth International Workshop on Helicobacter & Microbiota in Inflammation & Cancer
  • Place of Presentation: Rome, Italy
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Prevalence of Helicobacter pylori infection in children and “Test and Treat” to Junior high school students: Strategies for extermination of Gastric cancer in Japan (2014)
  • Author(s): Okuda M, Kikuchi S, Osaki T, Ueda J, Osaki K, Maekawa K, Yingsong Lin, Lin Y, Kamiya S, Fukuda Y.
  • Organizer: DDW2014
  • Place of Presentation: Chicago, USA
• [Presentation] Prevalence and incidence of Helicobacter pylori infection in Japanese children. (2013)
  • Author(s): Okuda M, Kikuchi S, Osaki T, Ueda J, Maekawa K, Lin Y, Kamiya S, Fukuda Y.
  • Organizer: 10th Japan-Korea Joint Symposium on Helicobacter Infection.
  • Place of Presentation: Seoul, Korea
• [Presentation] Prevalence of Helicobacter pylori infection in Japanese children. (2013)
  • Author(s): Okuda M, Kikuchi S, Osaki T, Ueda J, Maekawa K, Yingsong Lin, Lin Y, Kamiya S, Fukuda Y.
  • Organizer: European Helicobacter Study Group XXVIth International Workshop on Helicobacter and related bacteria in chronic digestive inflammation and gastric cancer.
  • Place of Presentation: Madrid, Spain
• [Presentation] Prevalence of Helicobacter pylori infection in children living in a rural area of Japan. (2013)
  • Author(s): Okuda M, Maekawa K, Fukuda F.
  • Organizer: 2013 Joint Meeting of 13th APPSPGHAN and 40th JSPGHAN.
  • Place of Presentation: Tokyo, Japan
• [Presentation] 篠山市における中学生ピロリ菌検診 : 胃癌予防に向けた試み． (2013)
  • Author(s): 奥田真珠美，福田能啓．
  • Organizer: 第45回日本小児感染症学会学術集会
  • Place of Presentation: 札幌