Abstract: TH-OR093
Lectin and Terminal Pathway Activation in Children with IgAN
Session Information
- Shaping Pediatric Kidney Disease: Developmental Insights, Stem Cell Systems, Novel Biomarkers, and More
October 22, 2026 | Location: Room 603, Convention Center
Abstract Time: 04:50 PM - 05:00 PM
Category: Pediatric Nephrology
- 1800 Pediatric Nephrology
Authors
- Sahu, Srishti, Universite de Montreal, Montreal, Quebec, Canada
- Côté, Kevin, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Lachize Neanne, Lison, Universite de Montreal, Montreal, Quebec, Canada
- Badie, Amandine, Universite de Montreal, Montreal, Quebec, Canada
- Mathieu, Hélène, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Monteiro, Renato C., Universite Paris Cite, Paris, Île-de-France, France
- Boyer, Olivia, Hopital Universitaire Necker-Enfants Malades, Paris, Île-de-France, France
- Hogan, Julien, Hopital Robert Debre, Reims, Grand Est, France
- Lapeyraque, Anne-Laure, Universite de Montreal, Montreal, Quebec, Canada
- Bonnefoy, Arnaud, Universite de Montreal, Montreal, Quebec, Canada
- Alexandra, Cambier, Universite de Montreal, Montreal, Quebec, Canada
Group or Team Name
- Laboratory of Dr. Cambier
Background
In IgA nephropathy (IgAN), lectin pathway activation is linked to poorer renal outcomes, yet its triggers remain unclear. Collectin11 (CL11) has emerged as a lectin pathway activator, while soluble CD89 (sCD89) contributes to inflammation in childhood IgAN (cIgAN). We investigated whether interactions between sCD89 and CL11 drive lectin pathway activation and downstream C5b9–mediated injury in cIgAN.
Methods
This prospective study included 51 cIgAN patients and 103 controls. Plasma and urine levels of CL11 and soluble C5b9 (sC5b9) were measured by ELISA and correlated with clinical, histological, and biological parameters. Renal biopsies were examined for CL11 and C5b9 depositions. Circulating immune complexes (CICs) were analyzed by HPLC and immunoprecipitation to detect CL11. Human mesangial cells (HMCs) were stimulated with recombinant sCD89 or cIgAN serum, and CL11 expression, secretion, and deposition were assessed by western blotting, ELISA, and immunofluorescence.
Results
In cIgAN, urinary and plasma sC5b9 correlated with proteinuria (both r>0.5, p<0.005). Plasma sC5b9 better predicted fibrosis than proteinuria (AUC 0.81,p<0.001 vs 0.65,p>0.05). High plasma sC5b9 linked to glomerular capillary C5b9 deposits, which associated with proteinuria and hematuria (both p<0.05), indicating barrier damage. Plasma sC5b9 also related to hematuria and Oxford scores (all p<0.01), with 250 ng/ml best discriminating severe disease. Plasma CL11 was elevated (p<0.0001), with glomerular deposition in 75% of patients. Plasma and urinary CL11 correlated with proteinuria (both r>0.5, p<0.005), and plasma CL11 associated with reduced eGFR, hematuria, and histological lesions (all p<0.01). Remarkably, strong correlations among plasma sC5b9, CL11, sCD89, and IgA-sCD89 complexes reveal a mechanistic link between complement activation and sCD89 pathology. For the first time, CL11 was identified within CICs, establishing it as a component of pathogenic ICs. Moreover, rsCD89 stimulation of HMCs induced CL11 expression, secretion, deposoition, identifying a cellular mechanism that may amplify lectin pathway activation in cIgAN.
Conclusion
sC5b-9 and CL-11 correlate with disease severity in cIgAN, supporting their use as complementary biomarkers and reducing reliance on kidney biopsy. The newly recognized interaction between CL-11 and sCD89 provides mechanistic insight into complement activation and highlights novel therapeutic targets.