| There is a high prevalence of undiagnosed PsA in psoriasis patients; therefore identifying soluble biomarkers for PsA will help in screening psoriasis patients for appropriate referral to a rheumatologist. Potential PsA biomarkers likely originate in sites of inflammation, such as inflamed joints and skin, and subsequently enter systemic circulation. Therefore, we aimed to discover novel biomarkers, to facilitate PsA recognition in psoriasis patients. To achieve this objective, quantitative proteomic analyses of synovial fluid (SF) samples and skin biopsies obtained from PsA patients were performed. SF was obtained from swollen knee joints of 10 PsA patients, and age/sex matched early osteoarthritis (OA) controls. Likewise, skin biopsies were obtained from involved and uninvolved skin of 10 PsA, and 10 age/sex matched psoriasis patients without PsA (PsC). Using strong cation exchange chromatography, followed by tandem mass spectrometry, we characterized the proteomes of pooled SF and pooled skin samples. Extracted ion current intensities were used to calculate protein abundance ratios, and utilized to classify upregulated proteins. Selected reaction monitoring assays were developed to quantify these potential PsA markers in individual patient samples. Verified markers were subsequently measured in serum samples from 100 PsA, 100 PsC patients, and 100 healthy controls, using commercially available or in-house developed enzyme-linked immunosorbent assays. We quantified a total of 443 and 1922 proteins in SF and skin extracts, respectively, but only 17 proteins represented upregulated proteins in PsA SF, while 47 proteins were specifically elevated in PsA-derived skin. SRM verification confirmed that 12 and 8 proteins were indeed elevated in an independent set of PsA SF and involved PsA skin, respectively. Based on the fold change between PsA and controls, the associated P-values, and the cellular localization, we ranked the proteins, and selected the following putative markers for validation in the serum - M2BP, CD5L, MMP3, CRP, MPO, and ITGB5. Increased levels of CRP, M2BP, MMP3, and ITGB5 were independently associated with PsA, when compared to PsC. ROC analysis of this model showed an AUC of 0.851 [95% CI (0.799, 0.904)]. Thus, serum CRP, M2BP, and ITGB5 are potential biomarkers of PsA in patients with psoriasis. |
