Work

Circulating NET-associated parameters across chronic inflammatory skin diseases: a comparative study

Year: 2026

Type: article

Abstract: Background Neutrophil extracellular traps (NETs) are important components of innate immunity and may contribute to immune dysregulation in chronic inflammatory skin diseases. However, circulating NET-associated profiles across dermatoses with distinct immunopathogenic characteristics remain incompletely characterized. This study aimed to compare circulating NET-associated parameters in hidradenitis suppurativa (HS), pyoderma gangrenosum (PG), vitiligo (VIT), and psoriasis (PsO). Methods Serum MPO–DNA complexes, representing circulating NET-associated remnants, peptidylarginine deiminase 4 (PAD-4), a NET formation-associated marker, and DNase I concentration, a NET-related regulatory marker, were measured using ELISA-based assays. Associations between NET-associated parameters and conventional inflammatory markers, including C-reactive protein (CRP) and absolute neutrophil counts, were also explored. Between-group differences were assessed using the Kruskal–Wallis test followed by post hoc multiple comparisons, while correlations were evaluated using Spearman's rank correlation with Benjamini–Hochberg false discovery rate correction. Analyses were exploratory and hypothesis-generating. Results Significant between-group differences were observed for MPO–DNA, DNase I, and PAD-4. MPO–DNA levels were significantly higher in moderate-to-severe PsO than in healthy controls, whereas no other pairwise differences reached statistical significance. DNase I concentrations showed a distinct pattern, with higher levels in HS, PG, and VIT than in selected psoriasis groups and/or healthy controls. PAD-4 levels were significantly higher in moderate-to-severe PsO than in VIT, mild PsO, and healthy controls, while PG showed higher PAD-4 levels than VIT. Correlations between NET-associated parameters and conventional inflammatory or clinical measures were generally limited and none remained statistically significant after correction for multiple testing. Conclusions Circulating NET-associated parameters differed across chronic inflammatory dermatoses, supporting heterogeneous rather than uniform NET-associated profiles. Moderate-to-severe psoriasis was characterized by higher MPO–DNA and PAD-4 levels relative to healthy controls, whereas HS, PG, and VIT showed comparatively higher DNase I concentrations in selected between-group comparisons. These findings indicate heterogeneity in circulating NET-associated parameters across diseases with distinct immunopathological backgrounds. However, the results should be considered exploratory and hypothesis-generating, as circulating surrogate markers cannot directly establish tissue-level NET formation or degradation. Further studies incorporating orthogonal NET-associated markers, functional assays, and tissue-level analyses are warranted.

Source: Frontiers in Medicine

DOI: 10.3389/fmed.2026.1918335

Authors: Joanna Czerwińska, Agnieszka Markiewicz, Alicja Frączek, Maja Kleniewska, Marta Kasprowicz-Furmańczyk, Agnieszka Owczarczyk-Saczonek

Institution: University of Warmia and Mazury in Olsztyn

Language: English

Topic: Neutrophil, Myeloperoxidase and Oxidative Mechanisms

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801