PMID- 26700586 OWN - NLM STAT- MEDLINE DCOM- 20160928 LR - 20220408 IS - 1096-0023 (Electronic) IS - 1043-4666 (Linking) VI - 78 DP - 2016 Feb TI - Serum proteomic analysis identifies interleukin 16 as a biomarker for clinical response during early treatment of rheumatoid arthritis. PG - 87-93 LID - S1043-4666(15)30115-0 [pii] LID - 10.1016/j.cyto.2015.12.002 [doi] AB - OBJECTIVES: To conduct a comprehensive quantitative proteomics analysis of novel serum protein biomarkers based on synovitis status associated with matrix metalloproteinase-3 (MMP-3) and to determine the clinical significance of these biomarkers in rheumatoid arthritis (RA). METHODS: Patients with untreated RA (n=28), primary Sjogren's syndrome (pSS) (n=30), and healthy controls (HCs) (n=30) were enrolled for the screening assay. A total of 1128 serum proteins were analyzed using the SOMAscan assay. Serum levels of MMP-3 and interleukin (IL)-16 were measured using a latex turbidimetric immunoassay and ELISA at baseline and 12weeks after treatment with methotrexate (MTX) for MTX-naive RA patients (n=28) or with the biologics tocilizumab (TCZ) (n=7), abatacept (ABT) (n=11) or infliximab (n=22) for MTX-inadequate response (IR) RA patients. Correlation analysis was conducted using Spearman's rank correlation method. RESULTS: Proteomics showed that serum IL-16 levels were most positively correlated with those of MMP-3 (rho=0.51, p<0.01) and were significantly increased in patients with untreated active RA compared to HCs (p<0.01) or those with pSS (p<0.01). IL-16 levels decreased following treatment in both the MTX-naive and MTX-IR groups. Regarding clinical response, fluctuations in IL-16 levels were positively associated with changes in clinical indicators, particularly the Clinical Disease Activity Index (rho=0.89, p<0.01) in the TCZ and ABT-treated group. However, no similar correlation was noted in MMP-3 and acute phase reactants in any groups. CONCLUSIONS: IL-16 was a more effective clinical parameter than MMP-3, C-reactive protein, or erythrocyte sedimentation rate in both MTX-naive and MTX-IR RA patients. IL-16 might be a useful biomarker for evaluating clinical response in RA patients. CI - Copyright (c) 2015 Elsevier Ltd. All rights reserved. FAU - Murota, Atsuko AU - Murota A AD - Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8552, Japan. Electronic address: atsukomurota@a3.keio.jp. FAU - Suzuki, Katsuya AU - Suzuki K AD - Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8552, Japan. Electronic address: katsuyas@z5.keio.jp. FAU - Kassai, Yoshiaki AU - Kassai Y AD - Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan. Electronic address: yoshiaki.kassai@takeda.com. FAU - Miyazaki, Takahiro AU - Miyazaki T AD - Inflammation Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan. Electronic address: takahiro.miyazaki@takeda.com. FAU - Morita, Rimpei AU - Morita R AD - Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8552, Japan. Electronic address: rimpeim@a7.keio.jp. FAU - Kondo, Yasushi AU - Kondo Y AD - Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8552, Japan. Electronic address: yasutonko@yahoo.co.jp. FAU - Takeshita, Masaru AU - Takeshita M AD - Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8552, Japan. Electronic address: takeshita02@hotmail.com. FAU - Niki, Yasuo AU - Niki Y AD - Department of Orthopedic Surgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8552, Japan. Electronic address: y-niki@keio.jp. FAU - Yoshimura, Akihiko AU - Yoshimura A AD - Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8552, Japan. Electronic address: yoshimura@a6.keio.jp. FAU - Takeuchi, Tsutomu AU - Takeuchi T AD - Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8552, Japan. Electronic address: tsutake@z5.keio.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151214 PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antirheumatic Agents) RN - 0 (Biomarkers) RN - 0 (Blood Proteins) RN - 0 (Interleukin-16) RN - 7D0YB67S97 (Abatacept) RN - B72HH48FLU (Infliximab) RN - EC 3.4.24.17 (MMP3 protein, human) RN - EC 3.4.24.17 (Matrix Metalloproteinase 3) RN - I031V2H011 (tocilizumab) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM MH - Abatacept/therapeutic use MH - Adult MH - Aged MH - Antibodies, Monoclonal, Humanized/therapeutic use MH - Antirheumatic Agents/*therapeutic use MH - Arthritis, Rheumatoid/*blood/*drug therapy MH - Biomarkers/blood MH - Blood Proteins/*analysis/immunology MH - Blood Sedimentation MH - Female MH - Humans MH - Infliximab/therapeutic use MH - Interleukin-16/*blood MH - Male MH - Matrix Metalloproteinase 3/blood MH - Methotrexate/therapeutic use MH - Middle Aged MH - *Proteomics MH - Statistics as Topic MH - Treatment Outcome OTO - NOTNLM OT - Biomarker OT - Interleukin-16 OT - Proteomics OT - Rheumatoid arthritis OT - Serum protein EDAT- 2015/12/25 06:00 MHDA- 2016/09/30 06:00 CRDT- 2015/12/25 06:00 PHST- 2015/07/08 00:00 [received] PHST- 2015/10/28 00:00 [revised] PHST- 2015/12/02 00:00 [accepted] PHST- 2015/12/25 06:00 [entrez] PHST- 2015/12/25 06:00 [pubmed] PHST- 2016/09/30 06:00 [medline] AID - S1043-4666(15)30115-0 [pii] AID - 10.1016/j.cyto.2015.12.002 [doi] PST - ppublish SO - Cytokine. 2016 Feb;78:87-93. doi: 10.1016/j.cyto.2015.12.002. Epub 2015 Dec 14.