2005 Fiscal Year Final Research Report Summary
The role of granzyme B in the autoimmune diseses
| Project/Area Number |
16590986
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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 |
膠原病・アレルギー・感染症内科学
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| Research Institution | Nagasaki University |
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Principal Investigator |
IDA Hiroaki Nagasaki University, Hospital of Medicine and Dentistry, Assistant professor, 医学部・歯学部附属病院, 助手 (60363496)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAKAMI Atsushi Nagasaki University, Hospital of Medicine and Dentistry, Lecturer, 医学部・歯学部附属病院, 講師 (90325639)
EGUCHI Katsumi Nagasaki University, Graduate School of Biomedical Sciences, professor, 大学院・医歯薬学総合研究科, 教授 (30128160)
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| Project Period (FY) |
2004 – 2005
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| Keywords | granzyme B / autoantibody / apoptosis / SjOgren's syndrome / SS-B (La) / NK cells / NK cell activity / Malignant lymphoma |
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| Research Abstract |
Granzyme B is a unique serine protease which plays a crucial role for target cell death. Granzyme B efficiently cleaves many prominent autoantigens, and the hypothesis that autoantibodies arise when cryptic determinants are revealed to the immune system has been proposed. In this study, we have identified novel apoptosis-specific autoantibodies directed against granzyme B-induced cleavage fragments (27kD) of the SS-B (La) autoantigen in sera from patients with primary sjogren's syndrome (SS). A 27 kD fragment was detected by western blotting using sera from 13 of 74 primary SS patients (16.9 %). This fragment was recognized by anti-La monoclonal antibodies. Blocking studies using recombinant La protein revealed that an apoptosis- specific B cell epitope was revealed and detected by serum antibodies from 4 of 13 primary SS patients. This represents the first report of detection of autoantibodies directed specifically against a granzyme B-induced cleaved form of the La autoantigen in sera from primary SS patients. Next, we compared the number of peripheral blood natural killer (NK) cells, NK cell activity, and expression of NK cell activating receptors in patients with primary SS vs. normal controls. We found that NK cell number, NK cell killing activity, and the expression of activating receptors CD2 and NKG2D were significantly decreased, and the expression of NKp46, as well as the percentage of apoptotic NK cells were significantly increased in primary SS patients compared with healthy controls. NK cell killing activity on a per cell basis was similar in SS patients and healthy controls. Our data suggest that reduced NK cell numbers, a probably result of apoptotic death, may contribute to impaired NK cell activity in patients with primary SS.
Granzyme B is only one of the protease, however, it plays a crucial role for target cell death, autoantibody production, and autoimmune progression or regulation.
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