2021 Fiscal Year Final Research Report
The pathological role of autoantibodies in systemic lupus erythematosus
| Project/Area Number |
19K08914
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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| Research Institution | Yokohama City University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中島 秀明 横浜市立大学, 医学研究科, 教授 (30217723)
桐野 洋平 横浜市立大学, 医学部, 講師 (50468154)
岳野 光洋 日本医科大学, 医学部, 准教授 (50236494)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 膠原病学 / 自己抗体 / TRIM21 / 抗SS-A抗体 |
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| Outline of Final Research Achievements |
The role of autoantibodies in the pathogenesis of systemic lupus erythematosus is unknown. In this study, we investigated whether serum anti-TRIM21 antibodies are taken up by cells and modulate the function of TRIM21 in cells. The results showed that TRIM21 regulates the differentiation of B cells into plasmablasts and the production of antibodies and that anti-TRIM21 antibodies in serum may be transferred into immune cells and inhibit TRIM21 function. The intracellular trafficking of antibodies was observed to be promoted by stimulation with Toll-like receptor ligands and interferons, suggesting that this phenomenon may be part of the mechanism underlying the onset and exacerbation of systemic autoimmune diseases caused by infectious diseases.
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| Free Research Field |
医歯薬学
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| Academic Significance and Societal Importance of the Research Achievements |
全身性エリテマトーデスにおいては病因が不明であることから現状においてまだ根本的な治療はなく，ステロイドや免疫抑制薬による対症療法に依存している．本研究によりTRIM21がB細胞の形質芽細胞への分化や抗体産生を調節する機能を持ち，血清中の抗TRIM21抗体が免疫細胞内に移行してTRIM21の機能を阻害する可能性があることが示されたため，TRIM21とその関連分子が新規治療薬の標的分子として，創薬に繋がる可能性が生まれた．抗TRIM21抗体と同様に，他の細胞内抗原に対する自己抗体の病原性についても細胞内での自己抗原と自己抗体の相互作用で説明できる可能性も生まれた．
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