# Commentary: Anti-endothelial cell antibodies in pathogenesis of vasculitis

## TL;DR

This paper discusses how vasculitis should be understood as a result of various biological pathways, not just immune-related causes.

## Contribution

The paper proposes a new classification system for vasculitis that integrates traditional and pathway-based approaches.

## Key findings

- Vasculitis is better seen as a final endpoint of diverse mechanisms, not just immune-mediated.
- A dual-layer classification system could improve diagnosis and treatment strategies.
- Multiple upstream pathways, including infection and complement-mediated ones, contribute to vasculitis.

## Abstract

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.