Session Type: Abstract Submissions (ACR)
Background/Purpose 14-3-3η is a ubiquitous intracellular chaperone protein that is expressed extracellularly in rheumatoid arthritis and mediates inflammatory cascades that result in expression of inflammatory factors and metalloproteinases. An autoantibody response (AAb) is elicited to a range of epitopes on the native protein both within and outside the ligand-binding groove. We aimed to determine whether autoantibodies to the native protein were generated in AS and which specific autoantibody might be associated with inflammation and have diagnostic and prognostic properties.
Methods Sera from 116 patients with AS followed prospectively and 106 healthy controls were screened against ten 14-3-3η peptides (Pan 1-10) using an electrochemiluminescent multiplex assay platform. Inflammation was assessed by CRP and MRI of the sacroiliac joint (SIJ) and spine, which was performed by two central readers and an adjudicator using the Spondyloarthritis Research Consortium of Canada (SPARCC) score. Radiographic progression over 2 years was assessed by two central readers and an adjudicator using the modified Stoke AS Spine Score (mSASSS). Patients had mean age of 39.7 years, 73% male, mean symptom duration 16.9 years, and 51 (44%) received TNF blocker therapy. Mean (SD) baseline mSASSS was 13.8 (17.6), mean change in mSASSS was 1.8 (2.7), and 52.5% had mSASSS change > 0. Mann-Whitney U-test was used to determine group differences and ROC analysis (AUC) was used to assess diagnostic utility. Potential associations were assessed by Pearson correlation. Multivariate regression analyses were used to examine associations significant in univariate analyses.
Results Discrimination by AUC ranged from 0.81-0.89 for all 10 autoantibodies (p<0.0001 for all). For example, median (SD) expression of the Pan-1 14-3-3η autoantibody was significantly higher in SpA than in healthy controls (838 U/ml (605-1287) vs. 456 U/ml (346-568), p=0.0001) and area under the ROC curve was 0.86, 95%CI (0.82-0.91). A cut-off of 803 U/ml delivered 95% specificity and 53% sensitivity (LR+ 11.2, LR- 0.5). For inflammation parameters, Pan-1 and Pan-5 correlated significantly with CRP (r=0.23,p=0.02; r=0.27,p=0.005) and Pan-1 correlated with SPARCC SIJ MRI score (r=0.21,p=0.04). For radiographic progression measured by change in mSASSS, significant correlations were observed with all 10 Pan specificities, notably, Pan-2 (r=0.39,p<0.0001), Pan-3 (r=0.34,p=0.0004), and Pan-10 (r=0.35,p=0.0003). Independent predictors of MRI inflammation were sex (p=0.006) and Pan 1 autoantibody (p=0.008) (adjusted for age, sex, symptom duration, CRP). Controlling for baseline mSASSS CRP, age, sex, symptom duration, and treatment, Pan antibodies were the only significant predictors of the change in mSASSS at 2 years in multivariate regression analysis: Pan composite score (p=0.001), Pan-1 (p=0.0008), Pan-2 (p=0.0001), Pan-3 (0.0005), Pan-10 (p=0.0003).
14-3-3η autoantibodies are novel serum markers that are differentially expressed in AS versus healthy controls. They are significantly associated with MRI inflammation and baseline expression of several autoantibody specificities predicts radiographic progression.
W. P. Maksymowych,
Augurex Life Sciences Corp,
Augurex Life Sciences Corp,
Augurex Life Sciences Corp.,
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ACR Meeting Abstracts - http://acrabstracts.org/abstract/autoantibodies-to-14-3-3%ce%b7-are-novel-biomarkers-associated-with-inflammation-and-radiographic-progression-in-ankylosing-spondylitis/