Abstract: SA-PO113
Accurately Representing the Heterogeneity of IgA1 O-Glycosylation in Patients with IgA Nephropathy
Session Information
- Clinical Glomerular Disorders: Biomarkers and Molecular Profiling
November 04, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Glomerular
- 1005 Clinical Glomerular Disorders
Authors
- Renfrow, Matthew B., University of Alabama at Birmingham, Birmingham, Alabama, United States
- Hargett, Audra A., University of Alabama at Birmingham, Birmingham, Alabama, United States
- Hall, Stacy D., UAB, Birmingham, Alabama, United States
- Julian, Bruce A., University of Alabama at Birmingham , Birmingham, Alabama, United States
- Novak, Jan, University of Alabama at Birmingham , Birmingham, Alabama, United States
Background
Patients with several autoimmune disorders, chronic inflammatory diseases, and some infectious diseases exhibit abnormal glycosylation of serum immunoglobulins and other glycoproteins. The biological functions of these modifications in health and disease continue to be a significant area of interest in biomedical research. Specifically, the task of defining site-specific glycoprotein heterogeneity is recognized as an area that still needs a considerable amount of effort to fully understand the role of glycan heterogeneity in biological processes and disease pathogenesis.
Methods
We have developed robust workflows for the analysis of the IgA1 clustered O-glycan heterogeneity in clinical samples from patients with IgA nephropathy (IGAN).
Results
IgAN is the leading cause of glomerulonephritis in the world with as many as 20-40% of patients progressing to end stage renal disease. Patients with IgA nephropathy have increased levels of nephritogenic circulating immune complexes that contain the immunoglobulin, IgA1. We and others have shown that IgA1 in patients with IgAN have altered O-glycan heterogeneity. This work demonstrates the progress we have made in characterizing the differing patterns of IgA1 O-glycan heterogeneity in patients with IGAN. IgA1 was isolated from serum of healthy controls and patients with IGAN, in order to determine each samples’ specific O-glycosylation profile. Each patient’s monomeric, polymeric, and circulating immune complex IgA1 were analyzed separately to determine if there was a difference in the glycan signature of the specific type of IgA1. The HR-MS profile of both the IGAN patients and healthy controls was also tested using existing lectin ELISA test for Gd-IgA1.
Conclusion
The detailed characterization of glycoprotein site occupancy and glycan heterogeneity is required for a better understanding of the biological roles of induvial glycoproteins and to determine the impact of the glycosylation on the proteins functionality. Our current results will demonstrate our ability to reliably provide quantitative comparison of individual sites of glycosylation across a range of O-linked glycosylation sites in order to determine a protein’s Glycan Signature and how that signature relates to the proteins function. This work is supported by the NIH (GM098539).
Funding
- NIDDK Support