Abstract: TH-PO0712
Plasma Proteome Profiling to Assess ANCA-Associated Vasculitis Disease Activity
Session Information
- Glomerular Innovations: Artificial Intelligence, Multiomics, and Biomarkers
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Jerke, Uwe, Experimental and Clinical Research Center (ECRC) and Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association and Charité, Berlin, Germany
- Kirchner, Marieluise, Core Unit Proteomics, Berlin Institute of Health (BIH) at Charité and MDC, Berlin, Germany
- Bartolomaeus, Theda Ulrike Particia, Experimental and Clinical Research Center (ECRC) and Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association and Charité, Berlin, Germany
- Kling, Lovis, Experimental and Clinical Research Center (ECRC) and Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association and Charité, Berlin, Germany
- Kratky, Vojtech, Department of Nephrology, General University Hospital and First Faculty of Medicine, Charles University in Prague, Prague, Czechia
- Tesar, Vladimir, Department of Nephrology, General University Hospital and First Faculty of Medicine, Charles University in Prague, Prague, Czechia
- Eckardt, Kai-Uwe, Nephrology and Medical Intensive Care, Charité, Berlin, Germany
- Schreiber, Adrian, Experimental and Clinical Research Center (ECRC) and Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association and Charité, Berlin, Germany
- Forslund, Sofia Kirke, Experimental and Clinical Research Center (ECRC) and Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association and Charité, Berlin, Germany
- Mertins, Philipp, Core Unit Proteomics, Berlin Institute of Health (BIH) at Charité and MDC, Berlin, Germany
- Kettritz, Ralph, Experimental and Clinical Research Center (ECRC) and Max Delbrück Center for Molecular Medicine (MDC) in the Helmholtz Association and Charité, Berlin, Germany
Background
Active anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) requires intensive immunosuppressive treatment that is de-escalated once patients achieve remission. Reliably diagnosing remission has therapeutic implications but remains challenging. We hypothesized that the plasma proteome harbors information that assist clinicians in diagnosing AAV remission.
Methods
The exploratory cohort included 116 and the independent validation cohort 108 AAV patients. We characterized plasma proteomes by untargeted Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) followed by targeted Parallel Reaction Monitoring–Mass Spectrometry (PRM-MS). Data were normalized, and de-confounded for general inflammation (CRP) and kidney function (eGFR). Feature reduction was performed by LASSO regression and Boruta analysis. A generalized linear model (GLM) was trained to diagnose AAV remission.
Results
Untargeted profiling revealed 300 differentially expressed proteins between active and remission AAV, with PCA showing excellent sample separation by disease state. After excluding CRP- and eGFR-confounders and applying LASSO regression, we identified 21 candidate proteins for remission diagnosis. PRM-MS validation and Boruta selection yielded a 7-protein panel. Training a GLM on this feature combination attained an AUC of 0.98 for distinguishing active and remission AAV in the exploratory cohort. Excellent GLM performance was confirmed in an external validation cohort (AUC 0.93). Applying the GLM to the 7-protein panel in the two combined cohorts showed an AUC of 0.97 and a positive predictive value for remission diagnosis of 87.2% thereby outperforming CRP and ANCA titer.
Conclusion
We established a robust 7-protein panel to diagnose AAV remission. This marker combination has the potential to individualize treatment in AAV patients.