Biomarkers in ANCA-Associated Vasculitis: Potential Pitfalls and Future Prospects

Abstract

Over the past three decades significant advancements in the understanding of the pathophysiology of ANCA-associated vasculitis has led to the development of a multitude of potential candidate biomarkers. Accompanied by the advent of increasingly effective therapeutic strategies, the need for a dependable biomarker to help determine the extent of disease activity and risk of relapse is ever-present. Their implementation would enable tailored therapy, optimising disease control whilst helping to mitigate unnecessary exposure to therapy and potential treatment related damage. Although far from perfect, ANCA serology and B-cell population are the two main staple biomarker tools widely used in practice to help supplement clinical assessment. Over recent years the application and progress of more novel biomarker tools have arisen in both organ limited and multisystem disease; including genomics, urinary proteins, degradation products of the alternative complement system, cytokines, metabolomics and biospectroscopy. Validation studies and clinical translation of these are required, with serial assessment of disease activity and determination of therapy according to biomarker status correlated with patient outcomes.

Pathogenesis of autoimmune disease

“…The role of LLPCs in many autoimmune responses is unclear because sequential autoantibody testing is often not performed after disease onset owing to the uncertainty of the role of antibodies as markers of disease activity or prognosis. For example, it has been difficult to establish whether ANCA testing helps to predict disease activity in ANCA vasculitis; the relationship between ANCAs and disease activity may vary depending on clinical manifestations (renal versus non-renal), the specificity of the autoantibodies (myeloperoxidase versus proteinase 3) and the performance characteristics of the assays 169 .…”

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 ].…”

Pathogenesis and biomarkers in ANCA-associated vasculitis

“…Occasional cases of "ANCA-negative" AAV are acknowledged, decreasing by the day with ANCA testing methodology improvement [36,37] . Falsenegative results can still be found because in some cases ANCA binds to the circulating ceruloplasmin [38] .…”