P023 Validation of a 14-3-3η autoantibody assay combined with CRP and HLA-B27 to improve axial spondyloarthritis detection

Background/Aims Axial spondyloarthritis (axSpA) is a chronic inflammatory disease with diagnostic delays that potentially lead to preventable spinal damage and poorer outcomes. Limited access to MRI and HLA-B27 testing contributes to these delays, and beyond CRP, no widely available blood tests support early identification. This study evaluates the diagnostic performance of 14-3-3η autoantibodies (AAbs) in a test and validation cohort and assesses the added patient capture rate when combining 14-3-3η AAbs with CRP and HLA-B27. Methods 14-3-3η AAb levels using a derived cut-off were measured on a novel multiplex bead-based assay in two axSpA cohorts from Edmonton (Modified New York Criteria): a test cohort (n = 105) and a validation cohort (n = 101). CRP (>5 mg/L being positive) and HLA-B27 status were available from the clinical dataset accompanying the patient samples. Statistical significance was set at p < 0.05. Results The cohorts were balanced in terms of most clinical variables, including sex distribution, CRP levels, HLA-B27 positivity, BASDAI, and mSASSS. The 14-3-3η AAb composite positivity was 66.7% in the test cohort and 57.7% in the validation cohort (p = 0.3134). Adding 14-3-3η AAb composite positivity to HLA-B27 and CRP status enhanced the patient capture rate for axSpA, increasing it from 93.3% to 99.0% in the test cohort and from 81.0% to 91.4% in the validation cohort (Table 1). HLA-B27 was negative in 17 and 20 patients in the test and validation cohorts, respectively. Adding 14-3-3η AAb composite positivity identified 70.6% and 55.0% of HLA-B27 negative patients in the test and validation cohorts. When combined with CRP in these HLA-B27-negative patients, the capture rate further increased to 88.2% in the test cohort while CRP didn’t capture any additional patients to 14-3-3η AAbs (55.0%) in the validation cohort. Conclusion This study highlights the value of adding 14-3-3η AAbs to CRP and HLA-B27 for axSpA evaluation, particularly in HLA-B27-negative patients. This approach may reduce diagnostic delays, enabling earlier treatment and improved outcomes. Future research will assess 14-3-3η AAb association with clinical, radiographic, and patient-reported outcomes. Integrating this assay into routine practice could optimize early detection and management of axSpA. Disclosure A. Marotta: Shareholder/stock ownership; Augurex Life Sciences Corp. W.P. Maksymowych: Consultancies; Augurex Life Sciences Corp, Abbvie, Eli-Lilly, Novartis, Pfizer, UCB, BMS, Celgene, Galapagos. R. Sengupta: Consultancies; Biogen, BMS, Abbvie, Pfizer, Novartis, Eli-Lilly, UCB. Honoraria; Augurex Life Sciences Corp. S. Bleakley: Corporate appointments; Augurex Life Sciences Corp. S. Wichuk: None. N. Biln: Shareholder/stock ownership; Augurex Life Sciences Corp.