Abstract: TH-PO0435
Circulating Low-Titer Antibodies Develop After Proteinuria in Nephrotic Syndrome from Hyposialylation-Related Neo-Epitopes and Disappear After Partial Sialic Acid Repletion
Session Information
- Glomerular Diseases: Autoimmune Diseases
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
- Chugh, Sumant S., Rush University, Chicago, Illinois, United States
- Ortega Lozano, Ariadna Jazmin, Rush University, Chicago, Illinois, United States
- Sanchez Gloria, Jose Luis, Rush University, Chicago, Illinois, United States
- Gomez-Sierra, Tania, Rush University, Chicago, Illinois, United States
- Zavala-Guevara, Itzel Pamela, Rush University, Chicago, Illinois, United States
- Mace, Camille E., Rush University, Chicago, Illinois, United States
- Molina-Jijon, Eduardo, Rush University, Chicago, Illinois, United States
- Clement, Lionel C., Rush University, Chicago, Illinois, United States
Group or Team Name
- Glomerular Disease Therapeutics Laboratory
Background
We have noted dozens of low titer antibodies in rat models of MCD and FSGS for at least two decades.
Methods
Since the common denominator between these conditions is glomerular hypo-sialylation, we studied whether presence of these antibodies could be correlated with the development and partial correction of hypo-sialylation injury. Nine month old female homozygous NPHS2-prom-Angptl4 transgenic rats (Clement Nat Med 2011) glomeruli were used as a source of hyposialylated proteins for Western blot studies and age and sex matched Sprague Dawley rat glomeruli for control normal sialylated protein.
Results
We used sera from nephrotic Buffalo Mna rats (FSGS model) from a 31 week long study in which anti-proteinuric effects of a sialic acid donor (SAD) or Control was tested. Since SAD dose was gradually increased till a therapeutic effect was noted, two specific time points, Day 63 and Day 121, at which the SAD had significantly lower proteinuria than Control (P<0.01, P<0.001 respectively) were studied. Western blot using these sera showed only minimal reactivity of nephrotic sera to WT Sprague Dawley rat glomerular protein at any stage. Both Control and SAD sera were reactive with transgenic rat protein on Day 63, suggesting that there were antibodies in both sera despite lower proteinuria in the SAD group. By Day 121, the reactivity of Control sera to transgenic rat protein had increased, whereas the SAD treated rat sera lost all reactivity to transgenic rat protein. Ongoing proteomic and Mass Spectrometry studies for target recognition of these low titer antibodies complement these observations.
Conclusion
In summary, low titer antibodies to glomerular proteins are a common consequence, rather than a cause of glomerular disease, resulting from prolonged or repeated hypo-sialylation injury related neo-epitope formation. These antibodies do not cause proteinuria, and partial and significant reduction of proteinuria using sialic acid donors precedes the decline in circulating antibodies. Longer use of sialic acid donors results in the complete loss of these circulating antibodies, suggesting the loss of neo-epitopes by partial sialic acid repletion.
Acknowledgment
R01DK128203, R01DK129522, R01DK137919, R01DK145476
Funding
- NIDDK Support