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Large-scale proteome profiling identifies circulating biomarkers for disease activity and organ involvement in ANCA-associated vasculitides

Hellbacher, Erik ; Knight, Ann ; Hemmingsson, Peter ; Juto, Anna ; Gunnarsson, Iva ; Bruchfeld, Annette ; Weiner, Maria ; Söderbergh, Annika ; Ohlsson, Sophie LU orcid and Pullerits, Rille , et al. (2026) In Frontiers in Immunology 17. p.1-10
Abstract

OBJECTIVE: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are chronic, relapsing inflammatory diseases, yet reliable biomarkers for detecting relapse and organ involvement remain limited. This study aimed to identify plasma protein biomarkers that distinguish active disease from remission and to explore markers associated with lung and kidney involvement.

METHODS: Plasma samples from 113 patients with granulomatosis with polyangiitis or microscopic polyangiitis (68 active disease and 45 remission) were profiled using a proximity extension assay targeting 181 inflammation- and cardiovascular-related proteins. Clinical data, including CRP and Birmingham vasculitis activity score (BVAS), were collected at... (More)

OBJECTIVE: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are chronic, relapsing inflammatory diseases, yet reliable biomarkers for detecting relapse and organ involvement remain limited. This study aimed to identify plasma protein biomarkers that distinguish active disease from remission and to explore markers associated with lung and kidney involvement.

METHODS: Plasma samples from 113 patients with granulomatosis with polyangiitis or microscopic polyangiitis (68 active disease and 45 remission) were profiled using a proximity extension assay targeting 181 inflammation- and cardiovascular-related proteins. Clinical data, including CRP and Birmingham vasculitis activity score (BVAS), were collected at sampling. Differential protein expression was assessed using ANOVA, with top candidates validated in independent sample cohorts (plasma samples,
n = 74; serum samples,
n = 34). Correlations with BVAS and CRP and discriminatory performance (AUC) were evaluated. Associations with chest- and kidney-specific BVAS were also examined.

RESULTS: A total of 57 proteins were differentially expressed between active disease and remission. Seven proteins (ST2, OPN, IL-2RA, CCL23, IL-6, Flt3L, and SCF) were validated in independent cohorts and showed strong associations with disease activity. Several demonstrated high discriminatory ability (AUC ≥ 0.80) between active disease and remission. Multiple proteins correlated with organ-specific BVAS scores: seven for chest involvement and 16 for kidney involvement, after adjustment for kidney function-related protein variation.

CONCLUSION: This study identifies a robust panel of plasma proteins that differentiate active AAV from remission and correlate with global and organ-specific disease activity. These biomarkers may enhance non-invasive disease monitoring and support earlier recognition of relapse and organ involvement in AAV.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Biomarkers/blood, Female, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/blood, Male, Middle Aged, Proteomics/methods, Proteome, Aged, Adult, Kidney/pathology
in
Frontiers in Immunology
volume
17
article number
1848693
pages
1 - 10
publisher
Frontiers Media S. A.
external identifiers
  • pmid:42327788
ISSN
1664-3224
DOI
10.3389/fimmu.2026.1848693
language
English
LU publication?
yes
additional info
Copyright © 2026 Hellbacher, Knight, Hemmingsson, Juto, Gunnarsson, Bruchfeld, Weiner, Söderbergh, Ohlsson, Pullerits, Eriksson, Sjöwall, Rantapää-Dahlqvist and Dahlqvist.
id
dbd1fc7c-e0de-4db6-9e93-00cddfba9d53
date added to LUP
2026-06-30 15:44:21
date last changed
2026-07-01 08:26:46
@article{dbd1fc7c-e0de-4db6-9e93-00cddfba9d53,
  abstract     = {{<p>OBJECTIVE: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are chronic, relapsing inflammatory diseases, yet reliable biomarkers for detecting relapse and organ involvement remain limited. This study aimed to identify plasma protein biomarkers that distinguish active disease from remission and to explore markers associated with lung and kidney involvement.</p><p>METHODS: Plasma samples from 113 patients with granulomatosis with polyangiitis or microscopic polyangiitis (68 active disease and 45 remission) were profiled using a proximity extension assay targeting 181 inflammation- and cardiovascular-related proteins. Clinical data, including CRP and Birmingham vasculitis activity score (BVAS), were collected at sampling. Differential protein expression was assessed using ANOVA, with top candidates validated in independent sample cohorts (plasma samples, <br>
 n = 74; serum samples,<br>
 n = 34). Correlations with BVAS and CRP and discriminatory performance (AUC) were evaluated. Associations with chest- and kidney-specific BVAS were also examined.<br>
 </p><p>RESULTS: A total of 57 proteins were differentially expressed between active disease and remission. Seven proteins (ST2, OPN, IL-2RA, CCL23, IL-6, Flt3L, and SCF) were validated in independent cohorts and showed strong associations with disease activity. Several demonstrated high discriminatory ability (AUC ≥ 0.80) between active disease and remission. Multiple proteins correlated with organ-specific BVAS scores: seven for chest involvement and 16 for kidney involvement, after adjustment for kidney function-related protein variation.</p><p>CONCLUSION: This study identifies a robust panel of plasma proteins that differentiate active AAV from remission and correlate with global and organ-specific disease activity. These biomarkers may enhance non-invasive disease monitoring and support earlier recognition of relapse and organ involvement in AAV.</p>}},
  author       = {{Hellbacher, Erik and Knight, Ann and Hemmingsson, Peter and Juto, Anna and Gunnarsson, Iva and Bruchfeld, Annette and Weiner, Maria and Söderbergh, Annika and Ohlsson, Sophie and Pullerits, Rille and Eriksson, Per and Sjöwall, Christopher and Rantapää-Dahlqvist, Solbritt and Dahlqvist, Johanna}},
  issn         = {{1664-3224}},
  keywords     = {{Humans; Biomarkers/blood; Female; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/blood; Male; Middle Aged; Proteomics/methods; Proteome; Aged; Adult; Kidney/pathology}},
  language     = {{eng}},
  pages        = {{1--10}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Immunology}},
  title        = {{Large-scale proteome profiling identifies circulating biomarkers for disease activity and organ involvement in ANCA-associated vasculitides}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2026.1848693}},
  doi          = {{10.3389/fimmu.2026.1848693}},
  volume       = {{17}},
  year         = {{2026}},
}