Serial Lipocalin 2 and Oncostatin M levels reflect inflammation status and treatment response in axial spondyloarthritis

Abstract

\n Background: Informative serum biomarkers for monitoring inflammatory activity and treatment responses in axial spondyloarthritis (axSpA) are lacking. We assessed whether Lipocalin 2 (LCN2) and Oncostatin M (OSM), both have roles in inflammation and bone remodeling, may accurately reflect chronic inflammation and treatment response in axSpA. Previous reports in animal models showed involvement of LCN2 and OSM in gut inflammation. We asked whether they also play a role in human axSpA.Methods. Analysis of a longitudinal observational axSpA cohort (286 patients) with yearly clinical assessments and concurrent measurements of serum LCN2 and OSM (1204 serum samples) for up to 12 years. Biomarkers levels were correlated with MRI scoring and treatment response. Results. Persistent and transient elevation of LCN2 and OSM were observed in axSpA patients. Persistent elevation of LCN2 or OSM, but not CRP, was correlated with sacroiliac joint MRI SPARCC scores (Pearson’s correlation p = 0.0005 and 0.005 for LCN2 and OSM respectively). We observed both concordant and discordant patterns of LCN2 and OSM in relationship to back pain, the cardinal clinical symptom in axSpA. 26% (73/286) of the patients remained both clinically and serologically active (CASA). 14% (40/286) of them remained clinically active with back pain, but were serologically quiescent (CASQ). 60% (173/286) of the patients became clinically quiescent, with back pain resolved, but 53% (92/173) of them were serologically active (CQSA). With respect to treatment responses, transient elevation of LCN2 or OSM over time was predictive of better response to all treatments. The data suggest that failure to normalize LCN2 and OSM indicates persistent chronic inflammation, as reflected by positive MRI imaging of the sacroiliac joints. Prevalence of severe ankyloses is comparable in CQSA and CASA patients, indicating that disease progresses even when back pain may be controlled (CQ)Conclusion. In axSpA, persistent LCN2 and/or OSM elevation reflects chronic SIJ inflammation and suboptimal treatment response. In our cohort, half of the currently deemed clinically quiescent patients with back pain resolved, continued to demonstrate chronic inflammation. LCN2 and OSM profiling outperforms CRP as a predictive measure and provides an objective assessment of chronic local inflammation in axSpA patients.