Genetics of vasculitis

PURPOSE OF REVIEW: Systemic vasculitis arises on a background of genetic predisposition shaped by HLA and non-HLA variations, triggered by environmental factors. This review summarizes recent genomic information translating molecular discoveries into clinical risk stratification. RECENT FINDINGS: In large vessel vasculitis group, giant cell arteritis is associated with MHC class II, especially HLA-DRB1*04 alleles. Somatic TET2 mutations increase the risk of GCA-associated vision loss. Association of some genetic variants with different subgroups of GCA was also reported. On the other hand, Takayasu arteritis is associated with MHC class I region, predominantly HLA-B*52, predicting aggressive vascular remodeling and the need for early surgical intervention. In medium-vessel vasculitis group, specific genetic factors, associated with polyarteritis nodosa (PAN) could not be shown. However, recessive CECR1 (ADA2) mutations define a monogenic mimic of PAN, known as DADA2, that manifests as early-onset strokes. In Kawasaki disease, a complex polygenic model exists involving HLA-DRB1*15:01 for susceptibility and HLA-DRB1*14:01 for coronary lesions. ANCA-associated vasculitis (AAV) better correlates with autoantibody status rather than with clinical phenotypes. PR3-ANCA exhibits a strong association with HLA-DPB1*0401 and SERPINA1 variants, predicting chronic relapses. MPO-ANCA is linked to HLA-DQ loci, predisposing patients to rapidly progressing glomerulonephritis. Association of certain HLA susceptibility markers with different subgroups of AAV was also reported. Finally, Behçet's syndrome exhibits strong epistatic interactions with HLA-B*51 and ERAP1. SUMMARY: Genomic mapping reveals not only associations of specific genetic variations with different vasculitis but also their effects to determine clinical subgroups, ischemic risk, and clinical outcomes.