Recent analyses of anti-endothelial cell antibodies (AECAs) have renewed interest in the immunological pathways underlying vascular inflammation. Although endothelial injury mediated by AECAs constitutes a clearly defined mechanistic contributor to a subset of vasculitic syndromes, accumulating evidence from virology, autoinflammation, complement biology, molecular genetics, and tissue injury suggests that vasculitis is better conceptualized as a final common pathological endpoint rather than a uniformly immune-mediated disease. In this perspective, we argue that the traditional immune-centric definition of vasculitis fails to encompass this mechanistic diversity. We outline multiple upstream mechanisms — including infection-driven, immune-complex–mediated, autoinflammatory, complement-mediated, monogenic, and injury-induced pathways — and propose a mechanism-informed nomenclature that integrates conventional vessel-size–based classification with pathway-based endotypes. This dual-layer approach may enhance diagnostic precision, improve biomarker interpretation, guide targeted therapeutic strategies, and better align vasculitis terminology with contemporary biological understanding.
Xie et al. (2026) studied this question.