Vasculitis update: pathogenesis and biomarkers

Paul Brogan, Despina Eleftheriou

Better understanding of the pathogenesis and treatment of primary systemic vasculitides (PSV) has led to the development of many potentially clinically relevant biomarkers. Genome-wide association studies have highlighted that MHC class II polymorphisms may influence the development of particular anti-neutrophil cytoplasmic antibody (ANCA) serotypes, but not the clinical phenotype of ANCA-associated vasculitis (AAV). Although ANCAs are overall poor biomarkers of disease activity, they may be useful for the prediction of flares of renal and/or pulmonary vasculitis. Moreover, patients with proteinase 3 (PR3)-AAV may respond better to rituximab than cyclophosphamide. Newer biomarkers of renal vasculitis in AAV include urinary soluble CD163, and may in the future reduce the requirement for renal biopsy. Better understanding of dysregulated neutrophil activation in AAV has led to the identification of novel biomarkers including circulating microparticles, and neutrophil extracellular traps (NETs), although their clinical utility has not yet been realised. Studies examining endothelial injury and repair responses have additionally revealed indices that may have utility as disease activity and/or prognostic biomarkers. Last, next-generation sequencing technologies are revealing monogenic forms of vasculitis, such as deficiency of adenosine deaminase type 2 (DADA2), and are profoundly influencing the approach to the diagnosis and treatment of vasculitis in the young.