Abstract: FR-PO0712
Deciphering A Proliferation Inducing Ligand's Involvement in the Pathogenesis of Childhood IgAN
Session Information
- Pediatric Nephrology: CKD, ESKD, and Glomerular Diseases
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Lachize Neanne, Lison, Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Mathieu, Hélène, Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Leenhardt, Diane, Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Badie, Amandine, Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Sahu, Srishti, Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Côté, Kevin, CHU Sainte-Justine Departement de pathologie, Montreal, Quebec, Canada
- Monteiro, Renato C., Centre de Recherche sur l'Inflammation, Paris, Île-de-France, France
- Boyer, Olivia, Hopital Universitaire Necker-Enfants Malades, Paris, Île-de-France, France
- Lapeyraque, Anne-Laure, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
- Alexandra, Cambier, Centre de Recherche du Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada
Background
IgA nephropathy follows a multi-hit development involving circulating immune complexes (CICs) containing Gd-IgA1 and sCD89, contributing to renal inflammation. A Proliferation-Inducing Ligand (APRIL) is suspected to contribute to the autoimmune response in adult IgAN. However, its involvement in childhood IgAN (cIgAN), often exhibiting more inflammation, remains unknown, as does its activation mechanism.
This study aims to clarify how APRIL is activated and determine its role in cIgAN.
Methods
We studied 86 cIgAN and 48 control patients from France and Canada. We quantified plasma and urinary APRIL levels and plasma CICs, and compared them to biological, clinical, and histological characteristics. Immunohistochemistry of cIgAN patients’ kidney biopsies was performed to visualize APRIL staining patterns. We also evaluated APRIL expression in mesangial cells (HMCs) after stimulation and assessed APRIL receptors presence on podocytes.
Results
We observed elevated levels of Gd-IgA1, sCD89-IgA1, sCD89 and circulating APRIL in the plasma, and circulating APRIL in the urine, of cIgAN patients compared to control (p<0.05). APRIL plasma levels correlated with histological inflammation (Oxford score).
Western Blotting suggested that APRIL is trapped within CICs, colocalizing with IgA in similar-sized complexes. ELISA and immunoprecipitations confirmed IgA-APRIL and CD89-APRIL complexes presence in cIgAN samples, correlating with plasma APRIL levels and being linked to worst initial clinical presentation and prognosis with kidney failure.
Immunostaining revealed APRIL deposits in the glomerular mesangium.
Stimulating HMCs with cIgAN plasma or recombinant sCD89 induced APRIL mRNA and protein production and its secretion. It induced the production of a new form of APRIL, the same one found in CICs. APRIL production by HMCs was confirmed by immunofluorescence.
TACI and BCMA seemed to be expressed by podocytes.
Conclusion
Our research highlights that APRIL is implicated in cIgAN pathogenesis, potentially activated by sCD89 in HMCs. We discovered a novel HMC-derived APRIL form, retained in CICs, which may participate in the mesangial-podocyte crosstalk. Finally, APRIL emerges as a candidate biomarker potentially reducing reliance on biopsy, and an interesting therapeutic target in cIgAN.