Distinguishing active from quiescent disease in ANCA-associated vasculitis using attenuated total reflection Fourier-transform infrared spectroscopy

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.

Classification of Systemic Lupus Erythematosus Using Raman Spectroscopy of Blood and Automated Computational Detection Methods: A Novel Tool for Future Diagnostic Testing

“…As the signal intensity of the scattered light is proportional to the concentration of a molecule within the sample, the overall Raman spectrum generated from an unknown sample can provide information on both its molecular constituents and the concentration of these present in the sample [ 15 ]. In summary, this rapid, label-free and cost-effective technique can provide a surrogate read-out to describe the metabolomic profile of a patient sample and has been successfully used across a wide area of clinical medicine, including complex disorders, such as Alzheimer’s disease [ 16 , 17 ], multiple sclerosis [ 18 ], primary immune deficiency [ 19 ], autoantibody-associated vasculitis [ 20 , 21 ], HIV/AIDS [ 22 ], diabetes [ 23 ] and carcinogenesis [ 24 , 25 , 26 , 27 , 28 ]. High diagnostic accuracy has been demonstrated for classification of numerous cancer types and other biological applications [ 29 , 30 , 31 , 32 , 33 , 34 ].…”

Automated Computational Detection of Disease Activity in ANCA-Associated Glomerulonephritis Using Raman Spectroscopy: A Pilot Study

“…Taking this into account, it should not dissuade further research in this area. Excellent results have previously been obtained from the spectrochemical interrogation of other biofluids including plasma and serum, demonstrating both infrared and Raman spectroscopy as viable non-invasive candidate biomarker tools of disease activity in AAV [ 27 , 28 ]. Additionally, in the present study, it is worth noting that there was some similarity in the key distinguishing spectral peaks between the two biological samples, with increased protein and cortisone expression observed in both tissue and urine for necrotising glomerular lesions.…”

Vibrational Biospectroscopy in the Clinical Setting: Exploring the Impact of New Advances in the Field of Immunology

“…Currently, FTIR has been used in the diagnosis of various conditions such as rheumatoid arthritis [18], HIV/ AIDs [19], diabetes [20], multiple sclerosis [21], mental health conditions [22], immune defciency [23], autoimmune vasculitis [24], and multiple cancer types [25][26][27]. In FTIR spectroscopy, some of the radiation absorbed is converted to vibrational energy within molecules in a sample.…”

“…Similar analysis was done on serum with peaks of 1659 cm −1 higher in active disease and peaks at 1311 cm −1 ,1441 cm −1 , and 1524 cm −1 higher in disease remission. Tis study was able to use Raman spectroscopy for both plasma (specifcity 93.3%, sensitivity 70%) and serum (specifcity 80%, sensitivity 80%) towards the diagnosis and treatment of AAV [24]. Morris et al performed a similar study to assess the use of FTIR spectroscopy in the diagnosis of AAV.…”