Abstract: FR-PO0716
Afucosylated IgG in Patients with Idiopathic Nephrotic Syndrome and Antinephrin Autoantibodies Correlates with Disease Activity
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
- Lugani, Francesca, Istituto Giannina Gaslini, Genoa, Liguria, Italy
- Spinelli, Sonia, Istituto Giannina Gaslini, Genoa, Liguria, Italy
- La Porta, Edoardo, Istituto Giannina Gaslini, Genoa, Liguria, Italy
- Rumeo, Noemi, Istituto Giannina Gaslini, Genoa, Liguria, Italy
- Granata, Simona, Universita della Calabria, Arcavacata di Rende, Calabria , Italy
- Gallon, Lorenzo G., University of Illinois Chicago College of Medicine, Chicago, Illinois, United States
- Zaza, Gianluigi, Universita della Calabria, Arcavacata di Rende, Calabria , Italy
- Verrina, Enrico E., Istituto Giannina Gaslini, Genoa, Liguria, Italy
- Bruschi, Maurizio, Universita degli Studi di Genova, Genoa, Liguria, Italy
Background
Idiopathic nephrotic syndrome (INS) is a glomerular disorder characterized by podocyte injury and proteinuria. Emerging evidence suggests that anti-nephrin autoantibodies (Abs) may contribute to disease pathogenesis in a subset of INS patients. However, variation in detection techniques and lack of urinary data have limited the reproducibility and interpretation of results. Additionally, while reduced IgG fucosylation enhances antibody-dependent cellular cytotoxicity in non-INS autoimmune diseases, its modulating anti-nephrin autoantibody function and disease severity in INS remains unexplored.
Methods
We analyzed serum and urine samples from pediatric and young adult patients with biopsy-proven focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD), stratified by disease activity (proteinuria-positive vs proteinuria-negative). Anti-nephrin Abs were assessed using conventional ELISA and immunoprecipitation with recombinant full-length FLAG-tagged human nephrin. The fucosylation profile of IgG autoantibodies was analyzed using Aleuria aurantia lectin (AAL) and Ulex europaeus agglutinin I (UEA-I).
Results
Anti-nephrin autoantibodies were detected in 11% of FSGS and 15% of MCD patients, with higher prevalence among those with nephrotic-range proteinuria. These autoantibodies were absent in healthy controls and in patients with membranous nephropathy or lupus nephritis. Autoantibody titers correlated with disease activity, decreasing during remission. ELISA and immunoprecipitation provided consistent results. In a subset of anti-nephrin-positive patients, antibodies were also detected in urine. Circulating anti-nephrin IgG exhibited significantly reduced antennary and core fucosylation.
Conclusion
Our findings confirm that anti-nephrin autoantibodies are associated with active disease in a subset of INS patients and can also be detected in urine. The correlation between ELISA and immunoprecipitation supports assay reliability. Importantly, altered IgG fucosylation may enhance the pathogenicity of anti-nephrin autoantibodies, providing mechanistic insights and identifying potential biomarkers and therapeutic targets in INS.
Funding
- Government Support – Non-U.S.