Towards a proteomic plasma biomarker panel for diagnosing vasculitis remission

Abstract

Abstract Active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) requires intensive immunosuppressive therapy, but continued treatment beyond remission risks serious harm. Because reliable biomarkers of remission are lacking, clinicians often prolong cost-intensive and toxic therapy unnecessarily. Here, we explore the plasma proteome to identify reliable biomarkers of disease remission in patients with AAV, adjusting for patient characteristics and clinical variables. Applying a two-tiered proteomics strategy that combines global discovery with targeted validation, we identify a protein signature of remission. We then implement the resulting 7-protein panel in a targeted mass spectrometry-based assay and confirm its diagnostic performance in an independent patient cohort. The panel consistently outperforms routine markers such as C-reactive protein and ANCA titer. Our findings suggest that this 7-protein panel provides a starting point for developing a clinical tool to support decision-making, with the potential to reduce treatment-related burden, mitigate toxicity, and lower healthcare costs. More broadly, our confounder-controlled proteomics approach provides a scalable blueprint for biomarker discovery in complex inflammatory diseases.