Etiology of fulminant type 1 diabetes -genetic and immunological analysis of PD-1

• Project/Area Number: 25860760
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Osaka Medical College
• Principal Investigator: Tsutsumi Chiharu 大阪医科大学, 医学部, 助教 (90636078)
• Research Collaborator: HANAFUSA Toshiaki ; IMAGAWA Akihisa ; HASEDA Fumitaka ; FUJISAWA Reiko
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 劇症1型糖尿病 / PD-1 / PD-L1 / PD-L2 / 自己免疫性1型糖尿病 / 全ゲノム解析 / 遺伝子

Outline of Final Research Achievements

In this study, we investigated PD-1, which plays an important role in T-cell immune regulation, from genetical and immunological aspects to elucidate the pathogenesis of fulminant type 1 diabetes (FT1D). We found that one polymorphism (7785C/T) in PD-1 gene was associated with autoimmune type 1 diabetes (T1AD), but not with FT1D. PD-1 positivity was significantly lower in CD4+ T-cells in patients with T1AD, but not in those with FT1D. In addition, PD-1 mRNA was significantly lower in CD4+ T-cells in patients with T1AD. These results indicate that low PD-1 expression may be associated with the destruction of beta cells in patients with T1AD via increased T-cell activation.

Research Products

• [Journal Article] Low PD-1 expression in peripheral CD4+ T-cells in Japanese patients with autoimmune type 1 diabetes. (2015)
  • Author(s): Fujisawa R, Haseda F, Tsutsumi C, Hiromine Y, Noso S, Kawabata Y, Mitsui S, Terasaki J, Ikegami H, Imagawa A, Hanafusa T.
  • Journal Title: Clin Exp Immunol Volume: Feb 12 Issue: 3 Pages: 452-457
  • DOI: 10.1111/cei.12603
  • Peer Reviewed / Open Access
• [Journal Article] 【糖尿病の治療の進歩】 1型糖尿病の診断と治療の進歩(解説/特集) (2014)
  • Author(s): 花房 俊昭, 堤 千春, 寺前 純吾
  • Journal Title: 日本医師会雑誌 Volume: 43 Pages: 1655-1659
• [Journal Article] 疾患と看護がわかる看護過程ナーシングプロセス 1型糖尿病(解説) (2014)
  • Author(s): 堤 千春, 花房 俊昭, 木原 知穂, 薬師神 裕子
  • Journal Title: クリニカルスタディ Volume: 35 Pages: 8-29
• [Journal Article] The cytokeratin-18 fragment level as a biomarker of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus. (2014)
  • Author(s): Miyasato M, Murase-Mishiba Y, Bessho M, Miyawaki M, Imbe H, Tsutsumi C, Tanimoto K, Imagawa A, Terasaki J, Hanafusa T.
  • Journal Title: Clinica Chimica Acta Volume: 433C Pages: 184-189
  • Peer Reviewed
• [Journal Article] Glycaemic instability correlates with a hyperglucagonaemic response in patients with type 1 diabetes without residual beta-cell function. (2013)
  • Author(s): Bessho M, Murase-Mishiba Y, Tsutsumi C, Haseda F, Imagawa A, Terasaki J, Hanafusa T.
  • Journal Title: Diabetes Research and Clinical Practice Volume: 102 (2)
  • Peer Reviewed
• [Journal Article] Glycated albumin as a useful clinical biomarker for glycemic variability in type 1 diabetes assessed by continuous glucose monitoring (2013)
  • Author(s): Tsutsumi C, Imagawa A, Onishi M, Sano H, Nakagawa S, Murase-Mishiba Y, Terasaki J, Hanafusa T
  • Journal Title: Diabetology International Volume: 4 (3) Pages: 156-159
  • NAID: 40019821763
  • Peer Reviewed
• [Presentation] 1型糖尿病におけるCD4+CD45RA+FOXP3low resting制御性T細胞の量的・質的検討 (2014)
  • Author(s): 長谷田 文孝, 今川 彰久, 堤 千春, 佐野 寛行, 三柴 裕子, 大西 峰樹, 寺前 純吾, 花房 俊昭
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] 自己免疫性1型糖尿病患者末梢血CD4陽性Tリンパ球におけるPD-1の低発現とPD-1遺伝子多型に関する検討(第2報) (2014)
  • Author(s): 藤澤 玲子, 長谷田 文孝, 堤 千春, 廣峰 義久, 能宗 伸輔, 川畑 由美子, 三井 しのぶ, 寺前 純吾, 池上 博司, 今川 彰久, 花房 俊昭
  • Organizer: 第57回日本糖尿病学会年次学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-05-22 – 2014-05-24
• [Presentation] 1型糖尿病患者末梢血のCD4陽性Tリンパ球におけるPD-1の発現 (2013)
  • Author(s): 藤澤玲子, 長谷田文孝, 堤千春, 廣峰義久,能宗伸輔, 川畑由美子, 三井しのぶ, 寺前純吾, 池上博司, 今川彰久, 花房俊昭
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本国際交流会館 [6F ホール]
• [Presentation] 日本人1型糖尿病におけるPD-1遺伝子多型の検討(第2報) (2013)
  • Author(s): 堤 千春, 今川彰久, 廣峰義久, 能宗伸輔, 川畑由美子, 三井しのぶ, 長谷田文孝, 寺前純吾, 池上博司, 花房俊昭
  • Organizer: 第56回日本糖尿病学会年次学術集会
  • Place of Presentation: 熊本国際交流会館 [6F ホール]
• [Presentation] Low expression of PD-1 in peripheral CD4＋ T-cells in Japanese patients with type 1A diabetes． (2013)
  • Author(s): Fujisawa R, Haseda F, Tsutsumi C, Hiromine Y, Noso S, Kawabata Y, Mitsui S, Terasaki J, Ikegami H, Imagawa A, Hanafusa T
  • Organizer: American Diabetes Association's 73rd Scientific Sessions
  • Place of Presentation: the McCormick Place Convention Center (West Building) in Chicago, IL.
• [Presentation] Low expression level of Peripheral CD4+PD-1+T-cells in Japanese Patients with Type 1A Diabetes (2013)
  • Author(s): Fujisawa R, Haseda F,Tsutsumi C, Hiromine Y, Noso S, Kawabata Y, Mitsui S, Terasaki J, Ikegami H, Imagawa A, Hanafusa T
  • Organizer: the 13th International Congress of the Immunology of Diabetes Society
  • Place of Presentation: Mantra Lorne, Victoria, Australia
• [Book] 「糖尿病学」2章「糖尿病の概念・疫学・診断・成因・病態」 5. 1型糖尿病―病態 (2015)
  • Author(s): 堤 千春、花房 俊昭
  • Total Pages: 17
  • Publisher: 西村書店