Development of the method to diagnose the prognosis of autoimmune disease by clarifying the pathologic factors.

通过明确病理因素，开发诊断自身免疫性疾病预后的方法。

• 批准号: 14370795
• 负责人: IWATANI Yoshinori
• 金额: $ 2.88万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370795/
• 关键词: autoimmune; thyroid; deep vein thrombosis; CD25+CD4+ cells; CD25+CD8+ cells; CD50+CD8+ cells; IgG3-secreting cells; interleukin-10 (IL-10); 予後診断法; CD30; CD4; CD8; IgG3; IgA; CD25+CD4+細胞; NKT細胞; 樹状細胞; CD30+CD8+細胞

To develop the diagnostic method for the prognosis of autoimmune disease, we investigated various immunoregulatory cells and molecules which may determine the pathogenesis and the prognosis of autoimmune disease, and clarified as follows.1.In autoimmune thyroid disease, the proportions of regulatory CD25+CD4+ cells and NKT cells were lower in thyroid than in blood, and there was a possibility that FasL+CD4+CD8+ dendritic cells may cause apoptosis of Fas+CD4+ cells in thyroid.2.Activated cytotoxic T cells and thyroid autoantibodies were independently involved in the development of hypothyroidism in Hashimoto's disease and a decrease of CD30 expression on CD30+CD8+ cells was also involved in this development.3.The number of IgG3-secreting cells and the level of IL-10 were involved in the intractability of Graves' disease under treatment with anti-thyroid drugs.4.Acquired activated protein C resistance was associated with anti-protein S antibody as a strong risk factor for deep vein thrombosis in non-SLE patients, and was associated with the co-existence of anti-prothrombin antibodies and lupus anticoagulant activity in SLE patients.

为了开发自身免疫性疾病预后的诊断方法，我们对可能决定自身免疫性疾病发病机制和预后的各种免疫调节细胞和分子进行了研究，并阐明如下：1.在自身免疫性甲状腺疾病中，甲状腺中调节性CD25+CD4+细胞和NKT细胞的比例低于血液中，并且有可能 FasL+CD4+CD8+树突状细胞可能引起甲状腺Fas+CD4+细胞凋亡。2.活化的细胞毒性T细胞和甲状腺自身抗体独立参与桥本病甲状腺功能减退症的发生，CD30+CD8+细胞上CD30表达的降低也参与了这一发展。3.IgG3分泌细胞的数量和水平 IL-10的升高与抗甲状腺药物治疗后Graves病的难治性有关。4.获得性活化蛋白C抵抗与抗蛋白S抗体作为非SLE患者深静脉血栓形成的强危险因素有关，在SLE患者中与抗凝血酶原抗体和狼疮抗凝活性并存有关。

项目成果

Watanabe, M., Yamamoto, N., Matsuzuka, F., Miyauchi, A., Iwatani, Y.: "Decrease of CD154 intensity of peripheral CD4+ T cells in autoimmune thyroid disease."Clin.Exp.Immunol.. (in press).

Watanabe, M.、Yamamoto, N.、Matsuzuka, F.、Miyauchi, A.、Iwatani, Y.：“自身免疫性甲状腺疾病中外周 CD4 T 细胞的 CD154 强度降低。”Clin.Exp.Immunol..（in

Shinoda R, et al.: "Physiological changes of Fas expression in peripheral lymphocyte subsets during the menstrual cycle"J Reprod Immunol. 60. 159-168 (2003)

Shinoda R 等人：“月经周期期间外周淋巴细胞亚群 Fas 表达的生理变化”J Reprod Nutrition。

Watanabe M, et al.: "Independent involvement of CD8^+CD25^+cells and thyroid auto antibodies in disease severity of Hashimoto's disease"Thyroid. 12. 801-808 (2002)

Watanabe M 等人：“CD8^ CD25^ 细胞和甲状腺自身抗体独立参与桥本氏病的疾病严重程度”甲状腺。

Nakamoto Y, et al.: "Increase of immunoglobulin G3-secreting cells in intractable Graves' disease"Thyroid. 13・4. 325-331 (2003)

Nakamoto Y 等人：“难治性格雷夫斯病中免疫球蛋白 G3 分泌细胞的增加”，甲状腺 13・4。

Nakamoto Y et al.: "Increase in immunoglobulin G3-secreting cells in intractable Graves' disease"Thyroid. 13. 325-331 (2003)

Nakamoto Y 等人：“顽固性格雷夫斯病中免疫球蛋白 G3 分泌细胞的增加”甲状腺。