Abstract: FR-PO826
Serum Levels of APRIL Correlate with Proteinuria in IgA Vasculitis: Findings from the GIGA-Kids Study
Session Information
- Glomerular Diseases: Inflammation and Immunology
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Blasco Pelicano, Josep Miquel, Columbia University Irving Medical Center, New York, New York, United States
- Berrouet, Cecilia C., Columbia University, New York, New York, United States
- Andrews, Lee G., Visterra Inc, Waltham, Massachusetts, United States
- Schachter, Asher Daniel, Visterra Inc, Waltham, Massachusetts, United States
- Chishti, Aftab S., University of Kentucky, Lexington, Kentucky, United States
- Hastings, Margaret Colleen, The University of Tennessee Health Science Center College of Medicine, Memphis, Tennessee, United States
- Flynn, Joseph T., Seattle Children's Hospital, Seattle, Washington, 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
- The GIGA-kids Study.
Background
IgA vasculitis (IgAV) is the most common systemic vasculitis in children and is characterized by variable kidney involvement. As in IgA nephropathy (IgAN), IgAV nephritis (IgAVN) is associated with increased levels of galactose deficient IgA1 (Gd-IgA1) and anti-glycan antibodies. While elevated levels of APRIL correlate with IgAN progression, the role of APRIL in IgAVN is unclear.
Methods
The GIGA-kids (Genomics of IgA-related disorders in kids) study aims to recruit 1,000 pediatric cases of IgAN and IgAV for genetic and biomarker studies. Here, we analyzed biomarkers for the first 495 GIGA-kids participants, including 54 with IgAV, 260 with IgAVN, 169 with IgAN, and 12 healthy pediatric controls. Serum levels of APRIL, Gd-IgA1, and anti-glycan-antibodies were measured in all 495 participants and correlated with disease status and severity.
Results
Among all biomarkers tested, serum levels of Gd-IgA1 were significantly elevated in IgAN and IgAVN cases compared to healthy controls (p=0.013, and p=0.0079, respectively). Neither Gd-IgA1 nor anti-glycan antibody levels correlated with proteinuria among IgAN or IgAVN cases. In contrast, APRIL levels were significantly associated with higher proteinuria in IgAVN before and after adjustment for age, sex, race/ethnicity and immunosuppression (p=0.0033 and p=0.0064, respectively). This association was not statistically significant in the IgAN cohort, which was potentially due to a smaller sample size and lower acuity of IgAN vs IgAVN.
Conclusion
Serum APRIL levels were positively correlated with proteinuria, and Gd-IgA1 levels were elevated in pediatric IgAVN, supporting the involvement of APRIL in the pathogenesis of nephritis. Therapeutic strategies targeting APRIL in IgAN may also benefit patients with IgAVN.
Funding
- Other NIH Support – Visterra