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Can we explain the varying pathologic processes of rheumatoid arthritis by CaMKII delta abnormality?

我们能否通过 CaMKII δ 异常来解释类风湿性关节炎的不同病理过程？

基本信息

批准号：
20591173
负责人：
KAWAKAMI Atsushi
金额：
$ 2.91万
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：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

项目摘要

We have examined the relationship between the pathogenesis of rheumatoid arthritis (RA) and CaMKII/PADIs/peptide citrullination/cellular abnormality of synovial cells and immune competent cells. Expression of PADIs in the rheumatoid synovial tissues remains to be clarified at present. According to our data, the expression of PADIs was weak whereas that of PADIs substrates were present in rheumatoid synovial cells. PADIs substrates in rheumatoid synovial cells could be citrullinated by interaction with neighboring immune competent cells, resulting in stimulation of anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies) in patients with RA. Our present data also suggested that the function of regulatory T cells (Treg cells), a major immune competent cell population, is down-regulated in patients with RA that may associate with perpetuation of the disease's process. However, further investigation is necessary to identify whether these phenomena are primary events or secondary results. In addition, the investigations regarding to the association of Treg cells with CaMKII/PADIs are also be necessary. In clinical study, we have identified a close association of MRI-proven bone edema with anti-CCP antibodies. At present, a detection of peptide citrullination is very difficult. Therefore, we are also going to solve this problem by immune complexsome analysis.

我们研究了类风湿关节炎（RA）的发病机制与CaMKII/PADI/肽瓜氨酸/滑膜细胞和免疫活性细胞的细胞异常之间的关系。PADI在类风湿关节炎滑膜组织中的表达目前尚不清楚。根据我们的数据，PADI的表达是弱的，而PADI的底物存在于类风湿性滑膜细胞。类风湿性滑膜细胞中的PADI底物可通过与邻近免疫活性细胞相互作用而被瓜氨酸化，从而刺激RA患者体内的抗环瓜氨酸肽抗体（抗CCP抗体）。我们目前的数据还表明，调节性T细胞（Treg细胞）的功能，一个主要的免疫活性细胞群体，下调与RA患者可能与疾病的过程的延续。然而，有必要进一步调查，以确定这些现象是主要事件还是次要结果。此外，Treg细胞与CaMK Ⅱ/PADI的相关性研究也是必要的。在临床研究中，我们已经发现MRI证实的骨水肿与抗CCP抗体密切相关。目前，瓜氨酸肽的检测非常困难。因此，我们也将通过免疫复合体分析来解决这个问题。