What does this research mean for the field?

A panel of seven plasma proteins, including ST2, OPN, IL-2RA, CCL23, IL-6, Flt3L, and SCF, reliably differentiates active ANCA-associated vasculitis from remission and correlates with organ-specific disease activity. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research aims to discover plasma protein biomarkers that differentiate between active disease and remission in ANCA-associated vasculitides.

June 9, 2026Open Access

Large-scale proteome profiling identifies circulating biomarkers for disease activity and organ involvement in ANCA-associated vasculitides

Key Points

This research aims to discover plasma protein biomarkers that differentiate between active disease and remission in ANCA-associated vasculitides.
Profiled plasma samples from 113 patients (68 active, 45 remission) using a proximity extension assay targeting 181 proteins.
Assessed differential protein expression using ANOVA and validated findings in independent cohorts (n=108).
Evaluated correlations with BVAS and CRP, and assessed discriminatory performance with AUC.
57 proteins were differentially expressed between active disease and remission.
7 proteins (ST2, OPN, IL-2RA, CCL23, IL-6, Flt3L, SCF) showed strong associations with disease activity and validated in independent cohorts.
Several proteins demonstrated high discriminatory ability (AUC ≥ 0.80) between active disease and remission.

Abstract

Objective Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are chronic, relapsing inflammatory diseases, yet reliable biomarkers for detecting relapse and organ involvement remain limited. This study aimed to identify plasma protein biomarkers that distinguish active disease from remission and to explore markers associated with lung and kidney involvement. Methods Plasma samples from 113 patients with granulomatosis with polyangiitis or microscopic polyangiitis (68 active disease and 45 remission) were profiled using a proximity extension assay targeting 181 inflammation- and cardiovascular-related proteins. Clinical data, including CRP and Birmingham vasculitis activity score (BVAS), were collected at sampling. Differential protein expression was assessed using ANOVA, with top candidates validated in independent sample cohorts (plasma samples, n = 74; serum samples, n = 34). Correlations with BVAS and CRP and discriminatory performance (AUC) were evaluated. Associations with chest- and kidney-specific BVAS were also examined. Results A total of 57 proteins were differentially expressed between active disease and remission. Seven proteins (ST2, OPN, IL-2RA, CCL23, IL-6, Flt3L, and SCF) were validated in independent cohorts and showed strong associations with disease activity. Several demonstrated high discriminatory ability (AUC ≥ 0.80) between active disease and remission. Multiple proteins correlated with organ-specific BVAS scores: seven for chest involvement and 16 for kidney involvement, after adjustment for kidney function-related protein variation. Conclusion This study identifies a robust panel of plasma proteins that differentiate active AAV from remission and correlate with global and organ-specific disease activity. These biomarkers may enhance non-invasive disease monitoring and support earlier recognition of relapse and organ involvement in AAV.

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