Abstract
The current lack of a reliable biomarker of disease activity in anti-neutrophil cytoplasmic autoantibody (ANCA) associated vasculitis poses a significant clinical unmet need when determining relapsing or persisting disease. In this study, we demonstrate for the first time that attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy offers a novel and functional candidate biomarker, distinguishing active from quiescent disease with a high degree of accuracy. Paired blood and urine samples were collected within a single UK centre from patients with active disease, disease remission, disease controls and healthy controls. Three key biofluids were evaluated; plasma, serum and urine, with subsequent chemometric analysis and blind predictive model validation. Spectrochemical interrogation proved plasma to be the most conducive biofluid, with excellent separation between the two categories on PC2 direction (AUC 0.901) and 100% sensitivity (F-score 92.3%) for disease remission and 85.7% specificity (F-score 92.3%) for active disease on blind predictive modelling. This was independent of organ system involvement and current ANCA status, with similar findings observed on comparative analysis following successful remission-induction therapy (AUC > 0.9, 100% sensitivity for disease remission, F-score 75%). This promising technique is clinically translatable and warrants future larger study with longitudinal data, potentially aiding earlier intervention and individualisation of treatment.
Highlights
Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) characterises an autoimmune disorder that results in inflammation and necrosis of small- and medium-sized blood vessels, causing potential multi-organ and life threatening disease
One hundred and eight participants are included in the present study; 25 with active disease (AD), 38 in disease remission (DR), 10 with membranous nephropathy (MM), five with minimal change disease (MCD), 10 with immunoglobulin A nephropathy (IgA), 10 with pre-renal acute kidney injury (AKI) in the context of infection and 10 healthy controls (HC)
The present study provides the first evidence that ATR-FTIR spectroscopy has the potential to provide an accurate biomarker of active disease and treatment response in multisystem AAV
Summary
Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) characterises an autoimmune disorder that results in inflammation and necrosis of small- and medium-sized blood vessels, causing potential multi-organ and life threatening disease. Advancements in instrumentation and computational chemometric analysis have enabled ATR-FTIR to be applied to a wide range of biofluids and tissue samples, across numerous medical disciplines Studies have employed it to detect disease with a high degree of sensitivity and specificity, including inflammatory arthropathy, neurodegenerative disease and m alignancy[7,8,9,10]. One previous study has applied ATR-FTIR spectroscopy in vasculitis, demonstrating promising results, with several characteristic spectral markers identified from urine in a rodent model of crescentic glomerulonephritis and patients with renal limited disease[20] This phase one proof-of-concept study aims to determine the potential use of ATR-FTIR spectroscopy in AAV as novel biomarker of disease activity, through analysis of a range of biofluids and correlation with clinical parameters from patients with multisystem disease
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