HSP 90-Alpha and Serotransferrin as Potential Biomarkers for Predicting IL-17 Inhibitor Response in Non-Radiographic Axial Spondyloarthritis: A Retrospective Analysis.

BACKGROUND

Non-radiographic axial spondyloarthritis (nr-axSpA) is an early stage of axial spondyloarthritis characterized by the absence of definitive radiographic changes. Interleukin-17 inhibitors (IL-17i) have shown efficacy in treating nr-axSpA, but a significant proportion of patients fail to respond. Identifying predictive biomarkers for IL-17i response is crucial for optimizing treatment strategies.

METHODS

This retrospective study analyzed pre-treatment serum samples from nr-axSpA patients treated with secukinumab. Responders (R) and non-responders (NR) were defined based on changes in ASDAS-CRP scores after 12 weeks of therapy. Serum protein profiles were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with label-free quantification, followed by validation of candidate proteins using enzyme-linked immunosorbent assay (ELISA). Statistical analyses included Student's t-test, Mann-Whitney U-test, and Spearman's correlation.

RESULTS

LC-MS/MS identified 47 differentially expressed proteins (DEPs) between R and NR groups, with 31 upregulated and 16 downregulated in NR. Seven proteins including heat shock protein HSP 90-alpha (HSP90α) and serotransferrin were selected for ELISA validation. ELISA confirmed significantly higher HSP90α (p = 0.027) and lower serotransferrin (p = 0.034) levels in NR compared to R. HSP90α showed a mild negative correlation with the reduction of BASDAI scores (r = -0.30, p = 0.035), while serotransferrin exhibited a mild positive correlation (r = 0.287, p = 0.048). Both proteins correlate mildly with the disease activity index.

CONCLUSION

Serum levels of HSP90α and serotransferrin may serve as potential biomarkers for predicting IL-17i treatment response in nr-axSpA patients. Elevated HSP90α and reduced serotransferrin levels may reflect chronic inflammation and disease activity, particularly from a subjective symptom perspective. Further validation in prospective studies is needed to confirm their utility in guiding personalized treatment strategies.