Pos1094 Autoantibodies to 14-3-3η in Axial Spondyloarthritis

Background: The pathophysiological role of the extracellular 14-3-3η antigen and the 14-3-3η autoantibodies (AAbs), that are raised to this normally intracellular protein, have been clinically characterized in rheumatologic autoimmune diseases. The 14-3-3η protein blood test is routinely used to assist with the diagnosis and monitoring of patients with rheumatoid arthritis (RA). We previously presented data on the expression of 14-3-3η AAbs in RA and axial spondyloarthritis (AS) using the Meso Scale Discovery® (MSD) research-use only (RUO) platform 1,2, where we showed the AAbs diagnostic and prognostic performance. 14-3-3η AAbs were differentially expressed in AS versus healthy controls and their levels were associated with the degree of SPARCC MRI SIJ inflammation and radiographic progression 1. There is a high unmet need for a reliable, easily accessible biomarker to aid in the accurate diagnosis of AS, particularly in people under the age of 45, when the disease is most amenable to treatment. Objectives: In this study, we compared the discriminative performance of the 14-3-3η AAb assay on Luminex®, a clinically ubiquitous and gold-standard multi-plex platform, versus the MSD RUO assay, to differentiate patients with AS from healthy controls (HC). Methods: AS patient samples were obtained from the Follow Up Research Cohort in Axial Spondyloarthritis (FORCAST) Prognostic Cohort. Available sera from 49 patients with AS and 25 healthy controls (HC), previously tested on MSD 1, were analyzed on a de novo Luminex 14-3-3η AAb assay. Cohort characteristics are described, and Spearman correlations were performed on variables of interest. AAb expression in U/µl on Luminex was compared in patients with AS versus HC. The Mann-Whitney U-test was used to determine group differences and ROC AUC analysis was used to test the discriminative performance of both assays. A subset ROC AUC analysis was performed in patients with AS aged 45 and under versus the HC. CRP positivity is defined as > 5 mg/L. Results: Patients with AS had a mean (SD) age of 44 (13) years and 67% were male. Median (IQR) for disease duration was 19 (10-24) years, for CRP was 9.6 (4.3 - 24.8) mg/L and for mSASSS score was 4.4 (2.0-29.5). Median (IQR) 14-3-3η AAb expression in patients with AS was significantly higher than in healthy controls at 136 U/µl (48 – 408) versus 54 U/µl (28 – 161), p=0.02. The ROC AUC for differential expression of 14-3-3η AAbs between AS and healthy controls for MSD RUO was 0.67 (95% CI, 0.55 - 0.79), p=0.02 and for Luminex was 0.66 (95% CI, 0.53 - 0.80), p=0.03. A ROC curve was run for the Luminex assay in the age subset ≤45 years for AS (n=29, 59% of AS) returning an AUC of 0.74 (95% CI, 0.61-0.88), p=0.003. The Youden Index corresponds to the best sensitivity and specificity of 69% and 72% for those Conclusion: The discriminatory performance of the 14-3-3η AAb assay based on the clinically ubiquitous Luminex platform was equivalent to MSD RUO for patients with AS versus healthy controls. Of interest is that 14-3-3η AAbs combined with CRP to identify 90% of patients with AS, underscoring the potential to combine these biomarkers for further research to investigate their complementary diagnostic and prognostic role in AS. REFERENCES: 1 Maksymowych WP, Wichuk S, Murphy M, Marotta A, Lambert, Robert. Autoantibodies to 14-3-3η Are Novel Biomarkers Associated with Inflammation and Radiographic Progression in Ankylosing Spondylitis. In: Spondyloarthropathies and Psoriatic Arthritis VI - Imaging and Biomarkers Internet. ACR/ARHP Annual Meeting; 2014. Available from: https://acrabstracts.org/abstract/autoantibodies-to-14-3-3η-are-novel-biomarkers-associated-with-inflammation-and-radiographic-progression-in-ankylosing-spondylitis/ 2 Maksymowych WP, Boire G, van Schaardenburg D, Wichuk S, Turk S, Boers M, et al. 14-3-3η Autoantibodies: Diagnostic Use in Early Rheumatoid Arthritis. J Rheumatol. 2015 Sep;42(9):1587–94. Acknowledgements: NIL. Disclosure of Interests: Anthony Marotta Augurex Life Sciences Corp., Augurex Life Sciences Corp., Augurex Life Sciences Corp., Walter P Maksymowych Augurex Life Sciences Corp., Augurex Life Sciences Corp., Stephanie Wichuk: None declared, Navneet Sidhu Augurex Life Sciences Corp.