S100 proteins in IgA vasculitis and other systemic vasculitides - from pathogenic mechanisms to clinical biomarkers: a systematic review.

BACKGROUND

IgA vasculitis (IgAV) is a small-vessel vasculitis characterized by immune complex deposition, neutrophil activation, and endothelial injury. S100 proteins are recognized mediators of inflammation and vascular damage; however, their specific biological and clinical relevance in IgAV remains incompletely understood.

OBJECTIVES

This systematic review aimed to synthesize current evidence on the mechanistic and clinical roles of S100 proteins in vasculitides, focusing on IgAV, and to evaluate their potential utility as biomarkers of disease activity, organ involvement, and prognosis.

METHODS

A PRISMA-compliant systematic search was conducted in PubMed, Embase, Scopus, and Web of Science up to November 18, 2025. Original human studies investigating S100A8/9, S100A12, S100A4, and S100A10 in any form of vasculitis or related vascular inflammation were included. Data were synthesized narratively following an independent risk-of-bias assessment.

RESULTS

Fifty-four studies met the inclusion criteria. Available evidence supports the role of S100A8/9 and S100A12 as markers of neutrophil-driven inflammation and disease activity in systemic vasculitides, with emerging evidence suggesting relevance in IgAV. In contrast, findings on S100A4 and S100A10 were fragmentary and indirect, indicating a mechanistic contribution but lacking sufficient IgAV-specific data.

CONCLUSIONS

S100 proteins may act as mediators in the IgAV inflammatory cascade. However, the current evidence base remains fragmented. Although S100A8/9 appears promising, standardized prospective studies are required for S100A12, S100A4, and S100A10 to establish their clinical validity for risk stratification.