Abstract: TH-PO0470
Serum A Proliferation-Inducing Ligand Levels Are Associated with Proteinuria in Children and Adolescents with IgA Vasculitis Nephritis
Session Information
- Glomerular Diseases: Clinical, Outcomes, and Therapeutics Research - IgAN
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Arace, Jeffrey, Columbia University, New York, New York, United States
- Taylor, Alexandria D., Columbia University, New York, New York, United States
- Dougherty, Julie, Nationwide Children's Hospital, Columbus, Ohio, United States
- Smoyer, William E., Nationwide Children's Hospital, Columbus, Ohio, United States
- Nelson, Raoul D., University of Utah Health, Salt Lake City, Utah, United States
- Kiryluk, Krzysztof, Columbia University, New York, New York, United States
Group or Team Name
- GIGA-Kids Study
Background
IgA vasculitis (IgAV) is the most common systemic vasculitis in children and is associated with variable kidney involvement. IgAV nephritis (IgAVN) shares a common pathogenic mechanism with IgA nephropathy (IgAN), characterized by overproduction of galactose-deficient IgA1 (Gd-IgA1). The cytokine A Proliferation-Inducing Ligand (APRIL) is a key driver of Gd-IgA1 production and has been linked to disease progression in IgAN. However, the role of APRIL in IgAVN remains unclear.
Methods
We analyzed biomarker data from participants in the GIGA-Kids (Genomics of IgA-related disorders in kids) study. Participants ≤25 years old with IgAN (n=110), IgAV (n=40), and IgAVN (n=227) who had serum APRIL and Gd-IgA1 levels measured within one year of diagnosis were included. Serum biomarkers were also analyzed in 121 healthy pediatric controls. Spot urine protein-creatinine ratio (UPCR) measurements were available for 120 IgAVN and 49 IgAN cases. Biomarker levels were compared across groups using linear regression adjusted for assay batch. Within IgAVN and IgAN, associations between biomarkers and log-transformed UPCR were assessed using multivariable linear regression adjusted for age, sex, race/ethnicity, immunosuppression, RAAS inhibition, and assay batch. Because APRIL levels differed systematically between assay batches, APRIL values were standardized within batches (z-scores).
Results
Serum Gd-IgA1 levels were significantly higher in IgAN, IgAV, and IgAVN compared with controls after batch adjustment (each p<0.001), with no differences seen between disease groups. Serum APRIL levels did not differ between disease groups and controls after adjustment for batch. In IgAVN, serum APRIL levels were significantly associated with higher proteinuria before and after adjustment for age, sex, race/ethnicity, immunosuppression, and RAAS inhibition (standardized β=0.31, p=0.046). This finding was consistent across batch-specific and pooled analyses. No association between APRIL and proteinuria was observed in IgAN (standardized β=-0.25, p=0.28). Gd-IgA1 was not associated with proteinuria in any disease group.
Conclusion
The significant association between serum APRIL levels and proteinuria in IgAVN suggests that APRIL may contribute to kidney injury in this disease. These findings support further investigation of APRIL as both a prognostic biomarker and a potential therapeutic target in children with IgAVN.
Funding
- Other NIH Support – Visterra