Abstract: TH-PO567
Identification of Circulating IgA Targeting Chemical Adducts in Patients with IgA Nephropathy
Session Information
- Glomerular Diseases: Omics, Biomarkers, and Tools
October 24, 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
- Alibrandi, Sara, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Molinari, Paolo, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Cravedi, Paolo, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Zorn, Emmanuel, Columbia University, New York, New York, United States
Background
IgA nephropathy (IgAN) is characterized by IgA accumulation in the mesangial area, leading to inflammation and kidney damage. Despite extensive research into its pathophysiology, the trigger for IgA production remains unclear. We hypothesized that the abnormal IgA levels in IgAN may result from a pathological immune response to post-translational protein modifications. To identify potential targets, we used a high-dimensional ELISA platform to assess IgA reactivity patterns in IgAN patients and controls towards post-translational protein modifications, building on our prior research.
Methods
A total of 28 patients with biopsy-proven IgAN and 22 healthy individuals were enrolled. Serum samples were analyzed using a high-dimensional ELISA platform to assess IgA reactivity to 93 natural chemical adducts. Statistical analyses were performed using Boruta algorithm to identify significant targets.
Results
Among the chemical adducts, carboxymethyl lysine (CML) emerged as a prominent target, with significantly higher IgA reactivity in IgAN patients. This reactivity was confirmed in an independent validation cohort of 15 cases and 15 controls and remained significant after adjusting for total IgA levels. IgG reactivity to CML did not differ between groups. Additionally, a positive correlation was observed between IgA reactivity to CML, serum CML levels and albuminuria in IgAN patients.
Conclusion
This study identifies CML as a potential target of IgA in IgAN. These findings highlight the possibility of using IgA reactivity to CML as a diagnostic biomarker for IgAN and provide new insights into the IgAN underlying mechanisms.