| Project/Area Number |
13671208
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | University of Yamanashi Faculty of Medicine |
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Principal Investigator |
KOBAYASHI Tetsuro University of Yamanashi, Faculty of Medicine, Professor, 医学部, 教授 (30113442)
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| Co-Investigator(Kenkyū-buntansha) |
中西 幸二 沖中記念成人病研究所, 研究員 (80211423)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | glutamic acid decarboxylase (GAD) / GAD antibody / type 1 diabetes / type 2 diabetes / HLA / epitope / epitope spreading / SPIDDM |
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| Research Abstract |
Disease-specific epitope profiles of glutamic acid decarboxylase (GAD) 65 autoantibodies (GAD65Ab) were studied in slowly progressive type 1 (insulin-dependent) diabetes mellitus (SPIDDM) and acute onset type 1 (insulin-dependent) diabetes mellitus (AIDDM) using seven kinds of GAD65/67 chimeric molecules. Sera obtained from Japanese SPIDDM (n = 17) and AIDDM (n = 46) patients followed prospectively were analyzed by immunoprecipitation, ELISA and western blotting.
GAD65Ab in all SPIDDM samples reacted specifically with an N-terminal linear epitope located on the membrane anchoring domain between amino acids 17-51 and C-terminal conformational epitope between amino acids 443-585 of GAD65. The binding of GAD65Ab with N-terminal 83 residues in SPIDDM inversely correlated with the period in which insulin was not required. GAD65Ab in AIDDM did not react with N-terminal epitope located between amino acids 1-83 irrespective of the titer of GAD65Ab. A novel epitope of GAD65Ab in AIDDM resided between amino acids 244-360 was identified in 17% (8/46) of patients whose age of onset was younger than other AIDDM patients.
In conclusion, GADAb in SPIDDM has unique N-terminal linear epitopes that are located on the anchoring domain of GAD65 molecules. Association is suggested between GAD65Ab targeted to this region and slowly progressive β-cell failure in SPIDDM.
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