B-181 Anti-14-3-3eta Autoantibodies: A Novel Diagnostic Biomarker that Discriminates Axial Spondyloarthritis from Mechanical Backpain

Abstract

People with axial spondyloarthritis (axSpA) typically present with persistent back pain and experience up to a 10-year diagnostic delay that may lead to irreversible spinal damage. A multiplex assay that measures anti-14-3-3eta (n) autoantibodies (AAbs) has been developed to aid clinicians with the diagnosis of axSpA. This is a high clinical unmet need for timely primary care referral of patients to a rheumatologist to reduce diagnostic delay. This study examines the discriminative performance of anti-14-3-3eta AAbs in patients with axSpA, including those with radiographic (r-) and non-radiographic (nr-) disease, compared to people with MBP. Patient serum (n=160) from the Bath Spondyloarthritis Biobank of patients referred for suspected or confirmed axSpA during routine clinical visits were selected based on sample availability. Patients had a rheumatologist confirmed diagnosis and met classification criteria for r-axSpA (modified New York criteria, n=55), nr-axSpA (ASAS 2009 criteria, n=54) or MBP (n=51). Anti-14-3-3eta AAb levels were measured using the multiplex assay. Logistic regression was performed to model the relationship between predictor variables and diagnosis. The probability formula generated from this regression was used to calculate a linear score for three models alongside variables of age, sex, CRP and HLA-B27: 1) all patients with axSpA (n=109), 2) r-axSpA, and 3) nr-axSpA versus MBP as a control group. The r-axSpA versus MBP regression was used to calculate anti-14-3-3eta AAb scores in banked serum samples from healthy individuals (n=100) for comparison. Statistical significance was set at p<0.05. Mean age (SD) was 55 (23) yrs for r-axSpA, 42 (14) yrs for nr-axSpA, and 30 (14) yrs for MBP. Gender distribution (% male) was respectively 67%, 41%, and 59%. Disease duration (SD) was 13 (27) yrs for r-axSpA, and 5 (5) yrs for nr-axSpA. HLA-B27 positivity status was: 69% for r-axSpA, 72% for nr-axSpA, and 18% for MBP. Anti-14-3-3eta AAb predictive model ROC AUCs for all axSpA versus MBP were 0.77, r-axSpA of 0.78 and nr-axSpA 0.73. Selecting the best sensitivity (SN) for ∼90% specificity (SP) returned SP and SN for: 1) all axSpA of 90% and 42%, 2) r-axSpA of 92% and 47% and 3) nr-axSpA of 92% and 38%. Corresponding Positive Predictive Values (PPV) were 88%, 83%, and 83%. In the All axSpA model, adding age and sex variables to the anti-14-3-3eta AAb score, improved the diagnostic odds ratio (DxOR) from 5.4 to 18.4 and increased to 23.4 with CRP added, and to 63.7 with HLA-B27 added. Scores for healthy controls were similar to patients with MBP, p>0.99. The anti-14-3-3eta AAb biomarker differentiates radiographic and non-radiographic-axSpA from MBP, achieves a high PPV and its discrimination improves when age, CRP, and HLA-B27 are added. Alongside these easily accessible patient variables at primary care, anti-14-3-3eta AAb may reduce diagnostic delay and complement HLA-B27.