Abstract: TH-PO0270
Patients with IgAN with Mesangial Hypercellularity Have Reduced Exposed N-Acetylgalactosamine (GalNAc) Residues of Galactose-Deficient IgA1 in Mesangial Immune-Complex Deposits
Session Information
- Glomerular Diseases: Cell Biology
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Novak, Lea, University of Alabama at Birmingham Health System, Birmingham, Alabama, United States
- Hall, Stacy D., University of Alabama at Birmingham Health System, Birmingham, Alabama, United States
- Cutter, Gary R., University of Alabama at Birmingham Health System, Birmingham, Alabama, United States
- Moldoveanu, Zina, University of Alabama at Birmingham Health System, Birmingham, Alabama, United States
- Qiu, Shihong, University of Alabama at Birmingham Health System, Birmingham, Alabama, United States
- Shang, Qiao, University of Alabama at Birmingham Health System, Birmingham, Alabama, United States
- Rizk, Dana V., University of Alabama at Birmingham Health System, Birmingham, Alabama, United States
- Julian, Bruce, University of Alabama at Birmingham Health System, Birmingham, Alabama, United States
- Green, Todd J., University of Alabama at Birmingham Health System, Birmingham, Alabama, United States
- Haas, Mark, Cedars-Sinai Medical Center, Los Angeles, California, United States
- Novak, Jan, University of Alabama at Birmingham Health System, Birmingham, Alabama, United States
Background
IgA nephropathy (IgAN) patients have circulating IgA1-containing immune complexes comprised of galactose-deficient IgA1 (Gd-IgA1), IgG autoantibodies specific for Gd-IgA1, and complement C3. Some circulating immune complexes accumulate in glomeruli and induce kidney injury. IgA1 proteins extracted from glomerular immune complexes are enriched for Gd-IgA1. Our previous studies support the nephritogenic role of Gd-IgA1-containing immune complexes. However, it is not known whether Gd-IgA1 molecules in the glomerular deposits have accessible GalNAc residues that are not covered by IgG autoantibodies or complement proteins. To address this question, we stained kidney-biopsy tissues of IgAN patients with anti-IgA antibody and GalNAc-specific lectin and used confocal microscopy to analyze their colocalization. Furthermore, colocalization results were correlated with Oxford classification MEST-C pathology scores.
Methods
Sections of residual frozen kidney-biopsy tissues of 19 IgAN patients were stained with anti-IgA antibody and GalNAc-specific lectin from Helix pomatia (HPA). ELISA confirmed recognition of Gd-IgA1 by HPA. Confocal microscopy revealed immune complexes in the mesangial areas and occasionally in glomerular capillary loops. For each slide, 60 IgA-positive regions of interest were selected in each group. Pearson’s correlation coefficient (PCC) was obtained for each region of interest to determine HPA-IgA colocalization. Mean PCC values for each HPA-IgA pairwise colocalization in mesangial areas and glomerular capillary loops groups were correlated with Oxford MEST-C scores.
Results
HPA-IgA colocalization between two groups correlated (P<0.0001) and showed lower colocalization in mesangial regions compared to capillary loops in all patients. For mesangial deposits, correlation with MEST-C scores showed lower HPA-IgA colocalization values in patients with mesangial hypercellularity (M1) score vs. M0 (P=0.044) consistent with reduction of exposed GalNAc residues of Gd-IgA1.
Conclusion
In summary, mesangial immune-complex deposits of IgAN patients with mesangial hypercellularity (M1) showed lower HPA-IgA colocalization corresponding to reduction of exposed GalNAc residues of Gd-IgA1, likely due to binding of additional molecules
that can exacerbate kidney injury.
Funding
- NIDDK Support