ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1152

Comprehensive Novel Proteomic Analysis of RA Synovial Fluid Highlights the Distinct Protein Profiles of Bone and Cartilage Metabolism

Yasushi Kondo1, Katsuya Suzuki1, Masaru Takeshita2, Yoshiaki Kassai3, Keiko Koga3, Yuumi Gotou4, Takahiro Miyazaki3, Rimpei Morita5, Yasuo Niki6, Atsuko Murota1, Ayumi Nishikawa1, Hironari Hanaoka1, Yuko Kaneko7, Hidekata Yasuoka7, Kunihiro Yamaoka1, Akihiko Yoshimura5 and Tsutomu Takeuchi8, 1Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, 2Division of Rheumatology and Clinical Immunology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan, 3Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., Kanagawa, Japan, 4Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, Tokyo, Tokyo, Japan, 5Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan, 6Department of Orthopaedic Surgery, Keio University, Tokyo, Japan, 7Division of Rheumatology, Keio University School of Medicine, Tokyo, Japan, 8Dept. of Internal Medicine, School of Medicine Keio University, Tokyo, Japan

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: , , ,

Session Information

Date: Monday, November 9, 2015

Title: Biology and Pathology of Bone and Joint Poster I: Osteoarthritis Pathogenesis

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

Growing interest has arisen in the search for specific pathophysiology and biomarker for rheumatoid arthritis (RA) utilizing synovial fluid (SF) proteomic analysis. However the difference of protein profiles between SF and serum is still unclear. The objective of this study was to clarify the difference of protein signatures in RASF and serum.

Methods:

SF was collected from 10 untreated RA patients and 10 osteoarthritis (OA) patients. Serum was collected from 30 untreated RA patients and 30 healthy controls (HC). Total of 1128 proteins were quantitatively measured by comprehensive high-throughput proteomics assay using nucleic acid aptamers (SOMAscan™ Assay; Somalogic Inc., CO, USA). Comparison pathway analysis was performed with Ingenuity Pathway Analysis (IPA; Ingenuity system, CA, USA) and statistically extracted differentially up- or down-regulated proteins (fold change >1.5 or <0.66, p<0.05) in RA SF compared to OA SF and RA serum compared to HC serum. 

Results:

A total of 167 of known pathways were extrapolated from RA SF, while only 23 pathways were extrapolated from RA serum (p<0.01 in the Benjamin-Hochman’s multiple testing correction). The inflammatory signaling pathway was extrapolated from both, RA SF and serum, however osteoblast, osteoclast and chondrocyte signaling pathway was uniquely extrapolated from RA SF (-log p value=13.2). Focusing on the SF proteins associated with bone and cartilage metabolism, bone morphogenic protein (BMP)-6, 7 which proteins promote osteogenesis and RANKL/RANK/OPG signaling proteins including osteoprotegerin were significantly lower in RA SF compared to OA SF. (p<0.05) Unexpectedly, dickkopf (Dkk)-1 and -4 those that negatively regulated Wnt signaling pathway were significantly suppressed in RASF. (p<0.05) Futhermore, BMP and Dkk family proteins negatively correlated with pro-inflammatory cytokines in RA SF especially IL-6 (range of r=-0.613 to -0.400, p<0.05).

Conclusion:

Novel proteomic analysis of the RA synovial fluid revealed the clear difference of protein expression in serum and SF, especially highlighting the distinct protein profiles of aberrant bone metabolic turnover and cartilage formation in RA affected joint.

Disclosure: Y. Kondo, None; K. Suzuki, None; M. Takeshita, None; Y. Kassai, Takeda Pharmaceutical Company Ltd, 3; K. Koga, Takeda Pharmaceutical Company Ltd, 3; Y. Gotou, Takeda Pharmaceutical Company Ltd, 3; T. Miyazaki, Takeda Pharmaceutical Company Ltd, 3; R. Morita, None; Y. Niki, None; A. Murota, None; A. Nishikawa, None; H. Hanaoka, None; Y. Kaneko, Abbvie, 5,Abbvie, Eisai Pharmaceutical, Chugai Pharmaceutical, Bristol Myers Squibb, Astellas Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Pfizer, Janssen, UCB., 8,Eisai Pharmaceutical, Chugai, Pharmaceutical, Astellas Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Pfizer, 9; H. Yasuoka, None; K. Yamaoka, Pfizer, Chugai Pharma, Mitsubishi-Tanabe Pharma, Takeda Industrial Pharma, GlaxoSmithKline, Nippon Shinyaku, Eli Lilly, Janssen Pharma, Eisai Pharma, Astellas Pharma and Actelion Pharmaceuticals., 8; A. Yoshimura, None; T. Takeuchi, Astellas Pharma, Bristol–Myers K.K., Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Eisai Co.,Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Santen Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co.,Ltd., Teijin Pharma Ltd., AbbVie GK,, 2,Astra Zeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., and Asahi Kasei Medical K.K.,abbivie GK, Daiichi Sankyo Co.,Ltd., Bristol–Myers K.K., Nipponkayaku Co.Ltd., 5,Mitsubishi Tanabe Pharma Co., Eisai Co., Ltd., Abbivie GK, 9,bbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Eisai Co., Ltd., Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., and Takeda Pharmaceutical Co., Ltd., Astellas Pharma, and Diaichi Sankyo Co.,Ltd. ,Celtrion , Ni, 8.

To cite this abstract in AMA style:

Kondo Y, Suzuki K, Takeshita M, Kassai Y, Koga K, Gotou Y, Miyazaki T, Morita R, Niki Y, Murota A, Nishikawa A, Hanaoka H, Kaneko Y, Yasuoka H, Yamaoka K, Yoshimura A, Takeuchi T. Comprehensive Novel Proteomic Analysis of RA Synovial Fluid Highlights the Distinct Protein Profiles of Bone and Cartilage Metabolism [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/comprehensive-novel-proteomic-analysis-of-ra-synovial-fluid-highlights-the-distinct-protein-profiles-of-bone-and-cartilage-metabolism/. Accessed .

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