Serum proteomic analysis identifies interleukin 16 as a biomarker for clinical response during early treatment of rheumatoid arthritis

• Published in: Cytokine (Philadelphia, Pa.) Vol. 78; pp. 87 - 93
• Main Authors: Murota, Atsuko, Suzuki, Katsuya, Kassai, Yoshiaki, Miyazaki, Takahiro, Morita, Rimpei, Kondo, Yasushi, Takeshita, Masaru, Niki, Yasuo, Yoshimura, Akihiko, Takeuchi, Tsutomu
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2016
• Subjects: Abatacept - therapeutic use; Adult; Aged; Antibodies, Monoclonal, Humanized - therapeutic use; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - drug therapy; Biomarker; Biomarkers - blood; Blood Proteins - analysis; Blood Proteins - immunology; Blood Sedimentation; Female; Humans; Infliximab - therapeutic use; Interleukin-16; Interleukin-16 - blood; Male; Matrix Metalloproteinase 3 - blood; Methotrexate - therapeutic use; Middle Aged; Proteomics; Rheumatoid arthritis; Serum protein; Statistics as Topic; Treatment Outcome; Biomarker; Interleukin-16; Serum protein; Rheumatoid arthritis; Proteomics
• ISSN: 1043-4666; 1096-0023; 1096-0023
• DOI: 10.1016/j.cyto.2015.12.002

•Given the comprehensive proteomics in serum samples from RA and controls to identify novel serum biomarkers based on synovitis status, IL-16 exhibited the highest correlation with MMP-3 in RA.•Regarding treatment with methotrexate or biologics in RA patients, fluctuation of IL-16 was well correlated with clinical response and a more effective clinical parameter than MMP-3, CRP or ESR.•This is the first study to identify changes in serum IL-16 levels in response to various therapeutic agents. 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). 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-naïve 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. Proteomics showed that serum IL-16 levels were most positively correlated with those of MMP-3 (ρ=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-naïve 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 (ρ=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. 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.