Background/Purpose: Reducing diagnostic delay for people presenting with back pain who have axial spondyloarthritis (axSpA) has become a clinical imperative since effective treatments can limit progression of this debilitative disease. The absence of a simple blood test that is accessible by referring primary care physicians contributes to this delay. We presented data from the Bath Spondyloarthritis Biobank demonstrating that 14-3-3η AAbs distinguish referred patients with axSpA from those with mechanical backpain (MBP), with an 88% PPV. This challenge also exists at the community rheumatologist level, where experienced interpretation of radiographs and MRI scans may be limited. This study evaluates the performance of the 14-3-3η AAbs in combination with existing clinical parameters in an established Edmonton radiographic (r-axSpA) patient cohort.

Methods: Serum samples from 159 patients with a rheumatologist confirmed diagnosis and classified as r-axSpA (AS-modified New York criteria) were tested on the anti-14-3-3η multiplex assay. The control group comprised the 51 MBP patients previously tested from the Bath cohort. The serum differential expression of 14-3-3η AAbs, CRP and HLA-B27 between patients with r-axSpA and MBP was evaluated by ROC AUC. Regression models combining the 14-3-3η AAb Score derived from the Bath study were tested in two predictive models: one with CRP and HLA-B27 markers only and the other adding Age and Sex variables. Corresponding specificity (SP), sensitivity (SN), predictive values (PPV, NPV), likelihood (LR) and diagnostic odds ratios (DxOR) are provided. The Akaike Information Criterion (AIC) statistical measure was reported to compare the relative quality of predictive models.

Results: Mean age of patients with r-axSpA was 42 (69% male) and for MBP, 30 years (59% male), (Table 1). Differential expression of each of the biomarkers delivered significant ROC AUCs; 0.70 for 14-3-3η AAbs, 0.81 for CRP and 0.84 for HLA-B27. The latter two delivered respectively higher DxOR (6.2, 11.1, 24.1) as expected, considering that they were used in patient diagnosis. The model that included the 14-3-3η AAb score with CRP and HLA-B27 added had better discrimination of patients with axSpA versus MBP with an AUC of 0.93 and DxOR of 39.6 that further improved to an AUC of 0.94 and DxOR of 95.3 when age and sex variables were added (Figure 1). As shown in Table 2, the AIC of the predictive models supported the full model as the best fit.

Conclusion: This study demonstrates that the 14-3-3η AAb score when added to currently used CRP and HLA-B27 markers, improves the differentiation of people with MBP from established r-axSpA. While the pretest probability of CRP and HLA-B27 performance is higher in this cross-sectional study than would be expected in an early referral cohort, including 14-3-3η AAb score may reduce diagnostic delay and potentially enable more confident and prompt initiation of therapy to improve outcomes.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-14-3-3-eta-aab-biomarker-improves-discriminative-performance-of-crp-and-hla-b27-to-differentiate-people-with-radiographic-axspa-from-those-with-mechanical-back-pain/