Similar and yet not quite the same: unmasking distinct type I interferon signatures in ANCA vasculitis

Antineutrophil cytoplasmic autoantibody–associated vasculitides can be classified by clinical phenotype or antineutrophil cytoplasmic autoantibody specificity, with overlapping yet distinct characteristics. Transcriptomic analyses of kidney biopsies from 2 French antineutrophil cytoplasmic autoantibody–associated vasculitis (AAV) cohorts revealed a pronounced type I interferon signature in microscopic polyangiitis (microscopic polyangiitis/myeloperoxidaseAAV) compared with granulomatosis with polyangiitis (granulomatosis with polyangiitis/proteinase 3-AAV). Among biopsies with high interferon scores, 66% were myeloperoxidase-AAV and 28% proteinase 3-AAV. The interferon score was associated with decreased kidney survival. These findings highlight AAV patient heterogeneity and support targeted treatment approaches.