Background The 14-3-3 protein family consists of seven highly conserved isoforms described as intracellular chaperones based on their ability to bind to a multitude of functionally diverse proteins. One isoform, 14-3-3η, is detected extracellularly in arthritis, behaves as an extracellular ligand which induces factors that contribute to joint damage and is expressed at higher levels in patients with erosive rheumatoid arthritis (RA). 14-3-3η levels correlate strongly with those of MMP-1 and MMP-3 in synovial fluid and serum further characterizing its biological expression and association with rheumatologic disease processes.
Objectives To explore 14-3-3η levels in erosive compared to non-erosive Psoriatic Arthritis (PsA) patients and its relationship with clinical variables.
Methods Sera of 24 patients (15 males and 9 females) with active PsA fulfilling the CASPAR classification criteria were evaluated for 14-3-3η concentrations using an investigational-grade 14-3-3η ELISA. Presence of 14-3-3η noted positivity for the biomarker. Of the 24 patients, as per radiographic assessment, 12 had erosive and 12 had non-erosive PsA. Clinical assessment included: SJC68, PASI, HAQ, CRP, ESR, DAS28. Two-tailed Mann-Whitney U-tests were run to compare group differences. Pearson correlations were generated to examine relationships between 14-3-3η and other clinical variables. Regression and contingency analyses were performed to identify which variables were associated with joint damage.
Results Median 14-3-3η serum concentrations were significantly higher in the erosive (0.23ng/ml) than non-erosive (0ng/ml) patients (p=0.026). Sixty-seven (67) % of the erosive patients were positive for 14-3-3η compared to 17% in the non-erosive group. As shown in Table 1 below, both groups were balanced in terms of their clinical characteristics. Across the whole cohort, 14-3-3η titres correlated moderately with CRP (r=0.429, p=0.03) and did not correlate with other clinical variables (DAS28, ESR, HAQ, PASI and SJC68), further underscoring its independence with other disease markers. Regression analysis revealed that 14-3-3η was independently associated with erosive status [likelihood ratio (LR) of 4.26 (p=0.039), an odds ratio of (OR) of 3.71 with an ROC AUC=0.74] while the other clinical variables did not, nor did they enhance 14-3-3η’s predictive utility. Contingency analysis evaluating the relationship between 14-3-3η positivity and erosive status demonstrates that 14-3-3η positivity reflects joint damage; delivering a LR=6.5 (p=0.013), a relative risk (RR) of 2.8 with an OR of 10.
Conclusions Extracellular 14-3-3η, which can be readily measured in patient serum, serves as an independent marker of joint damage in this PsA cohort. Taken together with the observed differences in expression in erosive RA, 14-3-3η should be further investigated as a promising candidate biomarker of joint damage.
Disclosure of Interest A. Marotta Shareholder of: Co-founder, A. Kuijk: None Declared, W. Maksymowych: None Declared, P. Tak: None Declared
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