Pathogenic role of newly identified regulatory molecule in autoimmune arthritis

新发现的调节分子在自身免疫性关节炎中的致病作用

• 批准号: 21591261
• 负责人: MATSUMOTO Isao
• 金额: $ 2.91万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591261/
• 关键词: リウマチ学; 関節リウマチ; TNFa; TIARP; シトルリン化蛋白; GPI; 自己抗体; ACPA; glucose-6-phosphate isomerase; TNFα; STEAP4

1)TIARP-/-mice developed spontaneous arthritis, had high serum levels of IL-6, increased CD11b+ cell count in the spleen, and showed enhanced TNF-induced IL-6 expression in macrophages. Sustained degradation of IkBa with dysregulated apoptosis was also noted in TIARP-/-macrophages, and they showed increased IL-6-induced STAT3 phosphorylation. These findings suggested that TIARP is a negative regulator in arthritis by suppressing IL-6 production, its signaling and TNFa-induced NF-kB signaling result in enhanced apoptosis in macrophages. 2)Nine cyclic citrullinated GPI peptides (CCG-1-9) were constructed. Samples were obtained from patients with RA (n=208), healthy subjects (n=174) and other autoimmune diseases (n=202). Anti-CCG-2, 4, 7 Abs were detected in about 30.0% patients with RA, and these Abs were very specific of RA (specificity 99%). Anti-CCG-2, 4, 7 Abs were correlated with anti-CCP, CEP-1 and the presence of HLA-DRB1 SE allele. Treatment with TNF antagonists significantly reduced the levels of anti-CCG-2, 7, suggesting possible diagnostic and activity marker of RA.

1)TIARP-/-小鼠出现自发性关节炎，血清IL-6水平升高，脾CD11b+细胞计数增加，巨噬细胞IL-6表达增强。TIARP-/-巨噬细胞持续降解IkBA并伴有细胞凋亡失调，表现为IL-6诱导的STAT3磷酸化增加。提示TIARP通过抑制IL-6的产生而在关节炎中发挥负性调节作用，其信号转导途径和TNFa诱导的NF-kB信号转导途径可促进巨噬细胞的凋亡。2)构建了9个环瓜氨酸化GPI多肽(CCG-1-9)。样本来自RA患者(n=208)、健康人(n=174)和其他自身免疫性疾病(n=202)。抗CCG-2、抗CCG-4、抗CCG-7抗体在RA患者中的阳性率约为30.0%，且对RA具有很强的特异性(特异性为99%)。抗CCG-2、抗CCG-4、抗CCG-7抗体与抗CCP、CEP-1和存在HLADRB1 SE等位基因相关。经肿瘤坏死因子拮抗剂治疗后，血清抗CCG-2、7水平显著降低，提示可能是RA的诊断和活动标志物。

项目成果

Comparison of low-field dedicated extremity magnetic resonance imaging with articular ultrasonography in patients with rheumatoid arthritis

类风湿性关节炎患者低场专用四肢磁共振成像与关节超声检查的比较

• DOI: 10.1007/s10165-010-0318-2
• 发表时间: 2011
• 期刊: Mod Rheumatol
• 影响因子: 2.2
• 作者: Horikoshi M;Suzuki T;Ikeda K;et al.
• 通讯作者: et al.

TIARPによる炎症性サイトカインの産生抑制

TIARP 抑制炎症细胞因子的产生

• 发表时间: 2011
• 作者: 井上明日香;松本功;住田孝之
• 通讯作者: 住田孝之

再発性多発軟骨炎GUIDELINE膠原病・リウマチ改訂第2版、小池隆夫、住田孝之編集

复发性多软骨炎指南胶原病/风湿病修订第 2 版，由 Takao Koike 和 Takayuki Sumita 编辑

• 发表时间: 2010
• 作者: 越智俊元;他;Minowa K;松本功
• 通讯作者: 松本功

日本臨床免疫学会雑誌

日本临床免疫学会杂志

• 发表时间: 2010
• 作者: 坪井洋人;松尾直美;飯塚麻菜;中村友美;松本功;住田孝之
• 通讯作者: 住田孝之

Overexpression of T-bet gene regulates murine autoimmune arthritis

• DOI: 10.1002/art.33335
• 发表时间: 2012-01-01
• 期刊: ARTHRITIS AND RHEUMATISM
• 作者: Kondo, Yuya;Iizuka, Mana;Sumida, Takayuki
• 通讯作者: Sumida, Takayuki