Multimodal Profiling of Complement Expression and Association With Outcomes in ANCA-Associated Vasculitis With Glomerulonephritis

@article{brilland2026multimodal,
  title = {{Multimodal Profiling of Complement Expression and Association With Outcomes in ANCA-Associated Vasculitis With Glomerulonephritis}},
  author = {Benoît Brilland and Victor Milon and Cyrille Vandenbussche and Nathalie Merillon and Eleonore Ourouda and Andrea Boizard-Moracchini and Maëva Roy and Odile Blanchet and Emeline Vinatier and Céline Beauvillain and Thomas Quéméneur and Assia Djema and Nicolas Henry and Giorgina Barbara Piccoli and Samuel Wacrenier and Yves Delneste and Patrick Blanco and David Langlais and Viviane Gnemmi and Marie-Christine Copin and Jean-François Augusto},
  journal = {Kidney international reports},
  year = {2026},
  month = aug,
  doi = {10.1016/j.ekir.2026.107056},
  url = {https://europepmc.org/article/PMC/PMC13657220},
  note = {CC BY},
}

TY  - JOUR
TI  - Multimodal Profiling of Complement Expression and Association With Outcomes in ANCA-Associated Vasculitis With Glomerulonephritis
AU  - Benoît Brilland
AU  - Victor Milon
AU  - Cyrille Vandenbussche
AU  - Nathalie Merillon
AU  - Eleonore Ourouda
AU  - Andrea Boizard-Moracchini
AU  - Maëva Roy
AU  - Odile Blanchet
AU  - Emeline Vinatier
AU  - Céline Beauvillain
AU  - Thomas Quéméneur
AU  - Assia Djema
AU  - Nicolas Henry
AU  - Giorgina Barbara Piccoli
AU  - Samuel Wacrenier
AU  - Yves Delneste
AU  - Patrick Blanco
AU  - David Langlais
AU  - Viviane Gnemmi
AU  - Marie-Christine Copin
AU  - Jean-François Augusto
PY  - 2026
DA  - 2026/08/26
JO  - Kidney international reports
DO  - 10.1016/j.ekir.2026.107056
UR  - https://europepmc.org/article/PMC/PMC13657220
AB  - Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with glomerulonephritis (AAV-GN) is classically considered pauci-immune, yet complement activation is a central pathogenic mechanism. Whether intrarenal complement-related transcriptional programs are reflected by conventional serum or immunofluorescence markers, and whether they are clinically informative, remains unclear. Methods: In 369 patients with AAV-GN from 2 independent retrospective cohorts, complement was assessed across circulating, histopathologic, and transcriptomic layers (serum C3/C4, glomerular C1q/C3 deposition, and targeted kidney transcriptomics). Predefined classical and alternative pathway-related expression scores were derived from intrarenal gene expression. Associations with severity and outcomes were evaluated using multivariable Cox models. Public spatial transcriptomic data sets provided validation and localization.  Results: Below-normal serum C3/C4 levels were uncommon. Low serum C3, but not C4, was associated with more severe kidney involvement, kidney failure (adjusted hazard ratio [aHR]: 2.0 [1.1-3.7]), and mortality (aHR: 2.3 [1.3-4.0]). Both glomerular C3 (47%) and C1q (11%) deposition identified more severe pathology and adverse outcomes. Compared with controls, AAV-GN kidneys showed increased complement-related expression-including classical pathway components, proximal alternative pathway genes (C3, C5AR1), and regulatory transcripts-that was only weakly concordant with serum or deposition markers. Low alternative pathway-related expression was independently associated with better kidney (aHR: 0.3 [0.1-0.7]) and overall (aHR: 0.4 [0.2-0.9]) survival. Spatial transcriptomics validated these signatures and suggested contributions from both immune and resident kidney compartments.
SN  - 2468-0249
ER  -