Commentary: Anti-endothelial cell antibodies in pathogenesis of vasculitis

Front Immunol. 2026 Mar 9:17:1750524. doi: 10.3389/fimmu.2026.1750524. eCollection 2026.

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.

Keywords: AECAs; chapel hill consensus; endothelial injury; endotype; mechanism-informed classification; nomenclature; vasculitis.

Publication types

  • Editorial
  • Comment

MeSH terms

  • Animals
  • Autoantibodies* / immunology
  • Biomarkers
  • Endothelial Cells* / immunology
  • Humans
  • Vasculitis* / diagnosis
  • Vasculitis* / etiology
  • Vasculitis* / immunology

Substances

  • anti-endothelial cell antibody
  • Autoantibodies
  • Biomarkers