Abstract: SA-OR065
Unraveling the Lectin Complement Pathway Dynamics in Childhood IgAN
Session Information
- Innovations in Pediatric Nephrology and Kidney Development
November 08, 2025 | Location: Room 371A, Convention Center
Abstract Time: 04:40 PM - 04:50 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Sahu, Srishti, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Côté, Kevin, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Lachize Neanne, Lison, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Badie, Amandine, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Mathieu, Hélène, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Leenhardt, Diane, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Boyer, Olivia, Institut Necker Enfants Malades, Paris, Île-de-France, France
- Lapeyraque, Anne-Laure, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Bonnefoy, Arnaud, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Alexandra, Cambier, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
Group or Team Name
- Cambier Laboratory.
Background
The lectin complement pathway is pivotal in the pathogenesis of IgA nephropathy (IgAN), yet the precise triggers of its activation remain unknown. Collectin11 (C11), a novel initiator of this pathway, has emerged as a focus of recent research. Concurrently, soluble CD89 (sCD89) has been implicated in kidney inflammation among childhood IgAN (cIgAN) patients. For the first time, this study unveils the intricate interplay between sCD89 and C11 as key drivers of lectin pathway activation, culminating in C5b-9 formation and triggering kidney inflammation.
Methods
We conducted a prospective study on one of the largest cIgAN cohorts (n=52), alongside 80 controls. Plasma and urinary C11 and soluble C5b-9 (sC5b-9) levels were quantified via ELISA and correlated with biological, histological, and clinical parameters. Kidney biopsies were analyzed for C5b-9 deposition. Human mesangial cells (HMCs) were assessed for C11 expression and secretion via western blotting, immunofluorescence, and ELISA following stimulation with cIgAN plasma or recombinant sCD89 (rsCD89). HPLC and immunoprecipitation identified C11 in circulating immune complexes (CICs).
Results
Elevated sC5b-9 levels correlated with proteinuria severity (r=0.558, p<0.005) and reliably predicted glomerulosclerosis (AUC=0.812, p<0.005), surpassing proteinuria. sC5b-9 levels were linked to glomerular inflammation (p<0.005), crescents (p=0.012), and capillary C5b-9 deposition (p=0.008). Plasma C11 levels were significantly higher in cIgAN patients (p<0.0001), contributing to proteinuria (r=0.520, p<0.005), inflammation (p=0.001), glomerulosclerosis (p=0.006), and crescents (p=0.013). Plasma sC5b-9, C11, sCD89, and IgA-CD89 complex levels showed strong positive correlations, indicating their role in cIgAN. For the first time, we identified C11 in CICs and confirmed its expression and secretion by HMCs. Its upregulation was induced by cIgAN plasma and rsCD89 stimulation, with colocalization alongside C3, supporting lectin pathway activation in cIgAN.
Conclusion
Plasma sC5b-9 levels above 250 ng/ml predict severe cIgAN, potentially reducing the need for invasive kidney biopsies. The interplay between C11 and sCD89 provides mechanistic insights into complement pathway activation and offers potential for targeted therapies.