Towards a proteomic plasma biomarker panel for diagnosing vasculitis remission

Abstract: Active autoimmune vasculitis requires intensive immunosuppressive therapy, but continued treatment after remission is achieved can cause serious harm. Reliable biomarkers to confirm remission are lacking, forcing clinicians to prolong cost-intensive and toxic therapy unnecessarily. Routine markers, such as C-reactive protein and anti-neutrophil cytoplasmic antibodies, lack sensitivity and specificity for the remission status, failing to guide treatment de-escalation safely. We hypothesized that the plasma proteome, when rigorously controlled for patient characteristics and clinical confounders, contains biomarkers that reliably diagnose remission in autoimmune vasculitis patients. To test this assumption, we applied a two-tiered proteomics strategy combining global discovery with targeted validation to identify a robust protein signature of remission. The resulting 7-protein panel was successfully implemented in a targeted mass spectrometry-based assay, with diagnostic performance confirmed in an independent patient cohort. The panel consistently outperformed routine markers. We propose this panel as a robust clinical tool to support decision-making, with the potential to reduce treatment-related burden, mitigate toxicity, and lower healthcare costs. Moreover, our confounder-controlled proteomics approach provides a scalable blueprint for biomarker discovery in complex inflammatory diseases.