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/myeloperoxidase-AAV) 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.