Background 14-3-3η (eta) is normally a ubiquitous intracellular protein whose extracellular expression in RA elicits a specific auto-antibody (AAb) response which is measured by immunoassay. The high diagnostic specificity and sensitivity of 14-3-3η AAbs' for early RA has been reported, wherein a positive signal was observed in Ankylosing Spondylitis (AS) compared to other disease controls. The most common early manifestation of AS reported at the primary care level involves lower back pain characterized by involvement of the sacroiliac joints (SIJ). There is a high unmet need for soluble biomarkers in AS to assist with identification of patients for rheumatology referral and prognosis, especially in the early stages where therapy can alter the disease course.
Objectives To determine the association of serum Pan 1 14-3-3η AAb peptide with SIJ inflammation and determine its utility for AS diagnosis and prognosis.
Methods Serum 14-3-3η Pan 1 AAb peptide (Pan 1) expression was evaluated in 116 AS patients diagnosed by the modified New York criteria, and in 106 healthy controls. AS patients had a median age of 41 years, 74% were male, and median symptom duration was 15.5 (8.8-24) years. A 2-tailed Mann-Whitney U-test was used to determine group differences in Pan 1 expression and a ROC curve was generated to establish its diagnostic utility for AS versus healthy controls. Pearson correlations were run to examine the relationship between Pan 1 and MMP-3, CRP and SIJ inflammation assessed using the SPARCC MRI SIJ inflammation score, mSASSS and change in mSASSS (ΔmSASSS). To further test the association of Pan 1 with either SIJ inflammation or ΔmSASSS, regression analyses were performed. For SIJ inflammation, symptom duration, CRP and MMP-3 were included in the model. For ΔmSASSS at 2 years, the contribution of Pan1 to a regression model that includes baseline mSASSS was analyzed.
Results Median (SD) 14-3-3η Pan 1 expression in the AS group was significantly higher in AS than in healthy controls; 838 U/ml (605-1287) vs. 456 U/ml (346-568), p=0.0001. The area under the ROC curve was 0.86, 95%CI (0.82-0.91) and at a cut-off of 626 U/ml delivered 82% specificity and 72% sensitivity. The Pearson correlations (r) for Pan 1 with SIJ inflammation were 0.44 (p<0.00001); CRP 0.23 (p=0.015); baseline mSASSS 0.18 (0.05); and ΔmSASSS 0.34 (p=0.001). Independent predictors of SIJ inflammation were symptom duration LR=9.3 (p=0.004) and Pan 1 LR=21 (p=0.0004). When controlling for baseline mSASSS, Pan 1 was the only significant predictor of the ΔmSASSS at 2 years LR=10.4 (p=0.002) in a stepwise regression.
Conclusions 14-3-3η Pan 1 auto-antibody peptide is a novel serum marker that is differentially expressed in AS versus healthy controls. Pan 1 is significantly associated with SIJ inflammation and its baseline expression is a predictor of ΔmSASSS at year 2.
Disclosure of Interest : W. Maksymowych Consultant for: Augurex Life Sciences Corp, S. Wichuk: None declared, M. Murphy Employee of: Augurex Life Sciences Corp, A. Marotta Employee of: Augurex Life Sciences Corp