Rationale and Design of the Orencia Atherosclerosis and Rheumatoid Arthritis Study (ORACLE Arthritis Study): Implications of Biologics against Rheumatoid Arthritis and the Vascular Complications, Subclinical Atherosclerosis

被引:2
作者
Ishigami, Tomoaki [1 ]
Nanki, Toshihiro [2 ]
Sugawara, Takuya [1 ]
Uchida, Kotaro [1 ]
Takeda, Hiroyuki [3 ]
Sawasaki, Tatsuya [3 ]
Chen, Lin [4 ]
Doi, Hiroshi [1 ]
Arakawa, Kentaro [1 ]
Saigo, Sae [1 ]
Yoshimi, Ryusuke [1 ]
Taguri, Masataka [1 ]
Kimura, Kazuo [1 ]
Hibi, Kiyoshi [1 ]
Wakui, Hiromichi [1 ]
Azushima, Kengo [1 ]
Tamura, Kouichi [1 ]
机构
[1] Yokohama City Univ, Grad Sch Med, Dept Med Sci & Cardio Renal Med, Kanazawa Ku, Yokohama 2360004, Japan
[2] Toho Univ, Dept Internal Med, Div Rheumatol, Sch Med,Ota Ku, Tokyo 1438541, Japan
[3] Ehime Univ, Proteosci Ctr, Matsuyama 7908577, Japan
[4] Nanjing Med Univ, Sir Run Run Hosp, Dept Cardiol, Long Mian Ave 109 Jiangning, Nanjing 210011, Peoples R China
关键词
atherosclerosis; rheumatoid arthritis; autoantibody; inflammation; autoimmune; clinical trial; extra-articular manifestation; abatacept; CTLA4-Ig (Cytotoxic T lymphocyte-associated antigen-4-Ig); ACCELERATED ATHEROSCLEROSIS; HEART-DISEASE; RISK;
D O I
10.3390/mps4040083
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
To explore the biological and immunological basis of human rheumatoid arthritis and human atherosclerosis, we planned and reported a detailed design and rationale for Orencia Atherosclerosis and Rheumatoid Arthritis Study (ORACLE Arthritis Study) using highly sensitive, high-throughput, human autoantibody measurement methods with cell-free protein synthesis technologies. Our previous study revealed that subjects with atherosclerosis had various autoantibodies in their sera, and the titers of anti-Th2 cytokine antibodies were correlated with the severity of atherosclerosis. Because rheumatoid arthritis is a representative autoimmune disease, we hypothesized that both rheumatoid arthritis and atherosclerosis are commonly developed by autoantibody-mediated autoimmune processes, leading to incessant inflammatory changes in both articular joint tissues and vessel walls. We planned a detailed examination involving carotid artery ultrasonography, measurements of adhesion molecules, such as ICAM-1 (intercellular adhesion molecule 1) and VCAM-1 (vascular cell adhesion molecule 1) for the evaluation of atherosclerosis progression, and high-throughput, high-sensitivity, autoantibody analyses using cell-free technologies, with detailed examinations of the disease activity of rheumatoid arthritis. Analyses of correlations and associations between biological markers and degrees of carotid atherosclerosis over time under consistent conditions may enable us to understand the biological and humoral immunity background of human atherosclerosis and autoimmune diseases.
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