Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis: where to go?

Abstract

Summary Enormous progress has been made during the last 25 years in our understanding of the aetiopathogenesis of the anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV). This has led to improvements in early diagnosis, treatment and secondary prevention of these diseases. Nevertheless, there are still unmet needs in the AAV. With respect to diagnosis and follow-up, sensitive biomarkers that reflect disease activity, also during smouldering disease, are needed. In the field of aetiopathogenesis, genetic and epigenetic studies are being performed not only directed at the autoimmune response but also at the expression of, possibly modified, autoantigens. Environmental factors, in particular microbial factors, are also being explored. This will enable analysis of gene–environment interactions in the AAV, so elucidating further their aetiopathogenesis. Explaining the differences in clinical presentation between proteinase 3 (PR3)-associated AAV and myeloperoxidase (MPO)-associated AAV requires an adequate animal model for PR3-ANCA disease, which is currently lacking. Although many large randomized controlled trials have built a base for a rational therapeutic approach in the AAV, late morbidity and mortality is still significant. The availability of new biologicals and the development of sensitive biomarkers for disease activity could further improve prognosis for patients suffering from AAV.