Background:Early diagnosis of psoriatic arthritis (PsA) can be facilitated by appropriate referral of psoriasis patients to rheumatologists. Soluble biomarkers for PsA may help screen psoriasis patients for PsA.Objectives:To identify novel biomarkers for PsA by investigating serum levels of candidate biomarkers identified through proteomic analysis of synovial fluid (SF) and skin biopsies and literature review.Methods:We first (discovery phase) identified markers using: i) proteomic analysis of SF1, ii) proteomic analysis of skin biopsies2, and iii) literature review. In verification phase 1, we measured serum levels of the selected potential protein markers, using commercially available ELISA kits, to identify differentially expressed markers in healthy controls and patients with PsA (≥3 swollen joints, not treated with biologics) and psoriasis without PsA (PsC; matched with PsA patients on age, sex and psoriasis duration) (100 subjects each group). In verification phase 2, using less strict criteria (no restriction on pharmacotherapy or disease activity) and larger sample size, we confirmed the association with PsA of markers identified in phase 1 using samples from 200 patients each with PsA and PsC. Statistical methods used included descriptive statistics, t-tests and logistic regression.Results:The discovery phase identified the following 31 markers for testing in verification phase 1- hsCRP, MMP3, CD5L, M2BP, MPO, ITGB5, DKK1, FGF23, IL-6, IL-1β, leptin, osteocalcin, OPG, OPN, SOST, TNFα, adiponectin, periostin, RANKL, YKL40, KLK6, KLK8, CS846, C2C, CPII, TNFSF14, COMP, ALP, CXCL10, S100A8/A9 and DEFA. The following 21 markers remained differentially upregulated in PsA after testing in verification phase 1- hsCRP, MMP-3, M2BP, ITGB5, leptin, OPG, OPN, SOST,TNFα, periostin, RANKL, YKL40, KLK8, C2C, CPII, TNFSF14, COMP, ALP, CXCL10, S100A8/A9 and DEFA. Univariate logistic regression analyses adjusted for age, sex, and disease duration confirmed the association between hsCRP, OPN, S100A8/A9, OPG and the ratio CPII/C2C in verification phase 2. Multivariate logistic regression demonstrated that hsCRP and OPN (both p<0.001) are independently associated with PsA.Conclusion:OPN, a cytokine involved in enhancing production of IFNγ and IL-12, reducing production of IL-10 and promoting attachment of osteoclasts to mineralized bone matrix, is a potential biomarker of PsA.References:[1] Cretu D, Prassas I, Saraon P, Batruch I, Gandhi R, Diamandis EP, Chandran V. Identification of psoriatic arthritis mediators in synovial fluid by quantitative mass spectrometry. Clin Proteomics. 2014 Jul 1;11(1):27.[2] Cretu D, Liang K, Saraon P, Batruch I, Diamandis EP, Chandran V. Quantitative tandem mass-spectrometry of skin tissue reveals putative psoriatic arthritis biomarkers. Clin Proteomics. 2015 Jan 13;12(1):1.Disclosure of Interests:Fatima Abji: None declared, Rohan Machhar: None declared, Kun Liang: None declared, Justine Ye: None declared, Katerina Oikonomopoulou: None declared, Vinod Chandran Grant/research support from: Abbvie, Celgene, Consultant of: Abbvie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lily, Janssen, Novartis, Pfizer, UCB, Employee of: Spouse employed by Eli Lily
Identification of psoriatic arthritis mediators in synovial fluid by quantitative mass spectrometry