Background/Purpose: Early intervention in axial spondyloarthritis (axSpA) may prevent pathogenic changes such as bone remodeling and spinal fusion. Unfortunately, early intervention is difficult, as there remains an average 5-10 year gap between onset of symptoms and diagnosis partly due to a lack of diagnostic biomarkers. Currently, diagnosis is based on a combination of clinical features, inflammatory markers, and imaging, as existing biomarkers such as CRP and HLA-B27 are not sensitive/specific enough alone. Ideally, a sensitive and specific biomarker could be used alongside existing tools to lessen the time to diagnosis. We hypothesized that metabolites, which can serve as markers of ongoing cellular functions that are likely altered in axSpA, would reveal a sensitive and specific biomarker that would differentiate axSpA cases from healthy controls.

Methods: Patients were selected from our ongoing mucosal studies cohort in which participants undergo colonic mucosal biopsies alongside blood draw. Healthy controls (n=24) were recruited from the endoscopy schedule while undergoing screening colonoscopies with biopsies and an additional blood draw, while axSpA cases (n=23) were recruited from rheumatology clinics and underwent a flexible sigmoidoscopy with biopsies and blood draw. AxSpA cases met ASAS criteria and had imaging consistent with the diagnosis of axSpA. Blood was drawn at the time of the endoscopy visit, then processed and stored. Collected plasma was analyzed by high-pressure liquid chromatography coupled with mass spectrometry (LC-MS).

Statistical analyses were performed using two-sided t-tests, principle component analysis (PCA), partial least squares discriminant analysis (PLSDA), and Receiver Operating Characteristics (ROC) analysis.

Results: PLSDA analysis showed good separation of groups, chiefly driven by oxalosuccinate and 3-sulfocatechol. Oxalosuccinate and 3-sulfocatechol levels significantly differed between axSpA and healthy controls (p: < 0.0001, p: < 0.0001). In ROC analysis oxalosuccinate had an area under the curve of 0.962, while 3-sulfocatechol had an AUC of 0.88. Oxalosuccinate alone outperformed any combination of other metabolites in correctly differentiating axSpA cases vs healthy controls, and did not significantly correlate with B27 status, BASDAI, endoscopy type, sex, or medication status.

Conclusion: Significant metabolic differences between axSpA and healthy controls were identified in our study, which may provide insight into the underlying pathophysiology of this disease. Furthermore and most strikingly, oxalosuccinate, a product in the TCA cycle, correctly differentiates axSpA from healthy controls and holds promise as a diagnostic biomarker. More work is needed to validate these results in another cohort and with additional controls as well as investigate the mechanism by which the TCA cycle is impacted in axSpA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/metabolomics-screening-in-axial-spondyloarthritis-identifying-potential-biomarkers/