Leveraging Genetic Findings for Precision Medicine in Vasculitis

Abstract

Vasculitides are a heterogeneous group of low frequent disorders, mainly characterized by the inflammation of blood vessels that narrows or occlude the lumen and limits the blood flow, leading eventually to significant tissue and organ damage. These disorders are classified depending on the size of the affected blood vessels in large, medium, and small vessel vasculitis. Currently, it is known that these syndromes show a complex etiology in which both environmental and genetic factors play a major role in their development. So far, these conditions are not curable and the therapeutic approaches are mainly symptomatic. Moreover, a percentage of the patients do not adequately respond to standard treatments. Over the last years, numerous genetic studies have been carried out to identify susceptibility loci and biological pathways involved in vasculitis pathogenesis as well as potential genetic predictors of treatment response. The ultimate goal of these studies is to identify new therapeutic targets and to improve the use of existing drugs to achieve more effective treatments. This review will focus on the main advances made in the field of genetics and pharmacogenetics of vasculitis and their potential application for ameliorating long-term outcomes in patient management and in the development of precision medicine.

Keywords: genome-wide association studies; immunochip; polymorphism; precision medicine; systemic vasculitis.

Figure 1

Timeline representing key events in vasculitis genetic research. HLA, human histocompatibility complex; BD, Behçet's disease; GCA, giant cell arteritis; AAV, ANCA-associated vasculitis; KD, Kawasaki's disease; TAK, Takayasu arteritis; GPA, granulomatosis with polyangiitis; GWAS, genome-wide association study.