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.

Tomoaki Ishigami,Toshihiro Nanki,Hiromichi Wakui,Kentaro Arakawa,Kengo Azushima,Hiroyuki Takeda,Masataka Taguri,Tatsuya Sawasaki,Sae Saigo,Kouichi Tamura,Ryusuke Yoshimi,Kiyoshi Hibi,Hiroshi Doi,Lin Chen ,Kôtarô Uchida ,Kensuke Kimura ,Takeshi Sugawara

doi:10.3390/mps4040083

Abstract

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.

Highlights

Rheumatoid arthritis (RA) is a representative autoimmune disease that affects approximately 700,000 individuals in Japan
Suppression of atherosclerosis in RA patients aimed at improving the prognosis of joints and for survival is considered an important open issue to evaluate the effects of anti-RA drugs in suppressing atherosclerosis, with a focus to achieve the improvement of the anti-atherosclerotic and survival-improving effects of these drugs, in addition to the improvement of articular prognosis [1,2,3]
We have demonstrated various autoantibodies that are involved in atherosclerosis, and applications for the registration of patents based on some of the findings of our studies have been filed to patent offices across the world [5]

Summary

Introduction

Rheumatoid arthritis (RA) is a representative autoimmune disease that affects approximately 700,000 individuals in Japan. RA is a serious and urgent issue in Japan because it affects both the individual patient’s abilities and the national workforce, and because of the national healthcare burden arising from increased social welfare expenditure (to cover the expenses of treatment, care, and so on). The availability of various antiinflammatory drugs in addition to molecular-targeted drugs and antibody preparations has made the control of joint destruction in RA patients to a level of RA remission practically feasible. Suppression of atherosclerosis in RA patients aimed at improving the prognosis of joints and for survival is considered an important open issue to evaluate the effects of anti-RA drugs in suppressing atherosclerosis, with a focus to achieve the improvement of the anti-atherosclerotic and survival-improving effects of these drugs, in addition to the improvement of articular prognosis [1,2,3]

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Conclusion