Kidney international · 2025
Complement activation drives a compartmentalized innate immune response in C3 glomerulopathy contributing to the disease phenotype.
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Meuleman Marie-Sophie, de Reyniès Aurélien, Mayinga Céline, Ngo Stéphanie, Rioux-Leclercq Nathalie, Vermorel Agathe, Olagne Jérome, Giovannini Diane, Francois Arnaud, Croué Anne, Planchard Gaëtane, Buob David, Delmas Yahsou, Courbebaisse Marie, Parfait Béatrice, Lebeaux David, Friedlander Gérard, Avramescu Marina, Brilland Benoit, Boulay Hugoline, Martins Manon, Roumenina Lubka, Frémeaux-Bacchi Véronique, Duong Van Huyen Jean-Paul, Chauvet Sophie
Аннотация
INTRODUCTION: C3 glomerulopathy is a rare kidney disease resulting from dysregulation of the complement alternative pathway. The mechanistic diversity of alternative pathway activation, the heterogeneous immunological and clinical profiles limit a comprehensive understanding of the disease.
METHODS: Here, we characterize mechanisms of complement-mediated immune response within the kidney. We studied a retrospective cohort of 47 patients diagnosed with C3 glomerulopathy and profiled systemic and intra-kidney complement activation and characterized intra-kidney immune infiltrates.
RESULTS: The immune infiltrate of the kidney showed distinct compositions between the glomerular and interstitial compartments, with most neutrophils and macrophages in the glomeruli versus a majority of B and T lymphocytes and macrophages in the interstitium. The presence of a neutrophil-rich glomerular infiltrate appeared to be associated with stronger markers of complement activation in both systemic and intra-kidney compartments. However, interstitial immune infiltrates were not associated with a specific complement activation profile. The presence of a neutrophil-rich glomerular infiltrate correlated with a better response of the kidney to treatment and kidney survival, while patients with higher interstitial infiltrate had poor kidney survival.
CONCLUSIONS: Our study highlights a link between the intra-kidney immune response, complement activation profile, and the phenotypic expression of the disease, which contributes to improving our understanding of the disease.
METHODS: Here, we characterize mechanisms of complement-mediated immune response within the kidney. We studied a retrospective cohort of 47 patients diagnosed with C3 glomerulopathy and profiled systemic and intra-kidney complement activation and characterized intra-kidney immune infiltrates.
RESULTS: The immune infiltrate of the kidney showed distinct compositions between the glomerular and interstitial compartments, with most neutrophils and macrophages in the glomeruli versus a majority of B and T lymphocytes and macrophages in the interstitium. The presence of a neutrophil-rich glomerular infiltrate appeared to be associated with stronger markers of complement activation in both systemic and intra-kidney compartments. However, interstitial immune infiltrates were not associated with a specific complement activation profile. The presence of a neutrophil-rich glomerular infiltrate correlated with a better response of the kidney to treatment and kidney survival, while patients with higher interstitial infiltrate had poor kidney survival.
CONCLUSIONS: Our study highlights a link between the intra-kidney immune response, complement activation profile, and the phenotypic expression of the disease, which contributes to improving our understanding of the disease.