Investigation of autoantigens in patients with rheumatoid arthritis through protemic analysis: exploration from diagnosis, pathogenesis to therapy

通过蛋白质分析研究类风湿性关节炎患者自身抗原：从诊断、发病机制到治疗的探索

• 批准号: 23591439
• 负责人: KAWAKAMI Atsushi
• 金额: $ 3.24万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591439/
• 关键词: リウマチ学; RA; 滑膜細胞; TSP-1; TGF-β1; VEGF; サイトカイン／増殖因子; 疾患活動性; パワードプラ; サイトカイン/増殖因子; seronegative RA; イムノコンプレキソーム; LC-MS/MS; PF-4; FLS; サイトカイン・増殖因子

Serum immune complexome analysis has found that TSP-1 and PF-4 are candidate autoantigens in RA. Especially, TSP-1 was considered as more useful than PF-4 in terms of detection sensitivity. In fact, prominent expression of TSP-1 was found in RA synovial tissues. TSP-1 was spontaneously produced in RA synovial cells and TGF- beta1 significantly stimulated the synthesis of TSP-1 at transcriptional level. A clear reduction of plasma TSP-1 and TGF- beta1 was found in RA patients successfully treated by disease-modifying anti-rheumatic drugs (DMARDs), however, the above change was not determined in RA patients DMARDs did not improve the clinical disease activity. It has been reported that the inflammatory niche of rheumatoid synovial tissues contain high TGF- beta1. We suspect that TGF- beta1 acts on synovial cells to produce TSP-1, and furthermore, the augmented production of TSP-1 may stimulate the autoantibody production toward TSP-1 in patients with RA.

血清免疫复合物组分析发现TSP-1和PF-4是RA的候选自身抗原。特别是，TSP-1被认为在检测灵敏度方面比PF-4更有用。事实上，TSP-1在RA滑膜组织中有显著表达。TSP-1在RA滑膜细胞中自发产生，TGF-β 1在转录水平显著刺激TSP-1的合成。经病情缓解抗风湿药物（DMARDs）治疗后，RA患者血浆TSP-1和TGF-β 1水平明显降低，但对RA患者无明显影响。据报道，类风湿性滑膜组织的炎性龛含有高TGF-β 1。我们怀疑TGF-β 1作用于滑膜细胞产生TSP-1，并且TSP-1的增加的产生可能刺激RA患者产生针对TSP-1的自身抗体。

项目成果

Adipogenesis of the mesenchymal stromal cells and bone oedema in rheumatoid arthritis

类风湿关节炎中间充质基质细胞的脂肪生成和骨水肿

• 发表时间: 2012
• 期刊: Clin Exp Rheumatol
• 影响因子: 3.7
• 作者: Okada A;Yamasaki S;Koga T;Kawashiri SY;Tamai M;Origuchi T;Nakamura H;Eguchi K;Kawakami A
• 通讯作者: Kawakami A

Immune complexome analysis for identifying immune complex antigens

用于鉴定免疫复合物抗原的免疫复合物组分析

• 发表时间: 2013
• 作者: Baba M;Ohyama K;Tamai M;Kishikawa N;Kawakami A;Kuroda N
• 通讯作者: Kuroda N

Evaluation of the patients with early arthritis by 2010 RA criteria in conjunction with MRI of wrists and finger joints

2010年RA标准结合腕指关节MRI对早期关节炎患者的评估

• 发表时间: 2011
• 作者: Tamai M;Kawakami A;Uetani M;Arima K;Nakamura H;Origuchi T;Aoyagi K;Eguchi K
• 通讯作者: Eguchi K

Musculoskeletal ultrasonography assists the diagnostic performance of the 2010 classification criteria for rheumatoid arthritis

• DOI: 10.3109/s10165-012-0628-7
• 发表时间: 2013-01
• 期刊: Modern Rheumatology
• 影响因子: 2.2
• 作者: S. Kawashiri;Takahisa Suzuki;A. Okada;S. Yamasaki;M. Tamai;Hideki Nakamura;T. Origuchi;A. Mizokami;M. Uetani;K. Aoyagi;K. Eguchi;A. Kawakami

関節リウマチ滑膜組織におけるThrombospondin-1(TSP-1)の重要性と調節機能の検討

类风湿性关节炎滑膜组织中血小板反应蛋白-1 (TSP-1) 的重要性和调节功能的检查

• 发表时间: 2013
• 作者: Takeshi Machida;Kiri Honma;Toshifumi Matsuyama;Katsuyuki Yui; Phil Ruiz;Teizo Fujita;Gary Gilkeson;and Hideharu Sekine;鈴木貴久,山崎聡士,中島好一,寳來吉朗,岡田覚丈,川尻真也,岩本直樹,一瀬邦弘,玉井慎美,有馬和彦,中村英樹,折口智樹,尾崎誠,大山要,黒田直敬,植木幸孝,江口勝美,川上純
• 通讯作者: 鈴木貴久,山崎聡士,中島好一,寳來吉朗,岡田覚丈,川尻真也,岩本直樹,一瀬邦弘,玉井慎美,有馬和彦,中村英樹,折口智樹,尾崎誠,大山要,黒田直敬,植木幸孝,江口勝美,川上純