Abstract: SA-PO0721
Comprehensive 21,000-Plex Proteome Profiling Reveals Canonical and Novel IgG and IgA Autoantibodies in Lupus Nephritis
Session Information
- Glomerular Diseases: Profiling Through Multiomics
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Madhusudan, Manisha, University of Houston College of Natural Sciences and Mathematics, Houston, Texas, United States
- Maruvada, Vinaika, University of Houston System, Houston, Texas, United States
- Ma, Yewei, University of Houston System, Houston, Texas, United States
- Mohan, Chandra, University of Houston System, Houston, Texas, United States
- Vanarsa, Kamala, University of Houston System, Houston, Texas, United States
Background
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the presence of autoantibodies, particularly nuclear components, leading to lupus nephritis (LN). Current diagnostic tests include the anti-dsDNA assay. To explore additional targets, a proteome-scale protein array profiling was performed.
Methods
We executed a 21,000-plex autoantibody screen (HuProt v4.0, CDI Labs) of serum from LN patients and healthy controls (N=8 each). Identified IgA, IgM and IgG autoantibodies that were significantly elevated in LN were annotated using REACTOME, KEGG, and WikiPathways. ELISA validation is ongoing.
Results
IgG autoantibody profiling confirmed known antigens (La, Sm, Sm/RNP, PARP1, IFNA1) and revealed novel targets involved in key pathways (e.g., AHCYL1, SH2B1, SETD7). Additional uncharacterized proteins such as SNRPA, DAP, and POTEG were identified. IgM reactivity included known (Sm, GLUL) and novel targets (POLB, CASP4), alongside unannotated proteins like CCBL2 and CT55. IgA analysis revealed classic targets (SSB, TROVE2) and pathway-linked proteins (CFP, ASPN, SPRTN), as well as novel proteins like WBSCR16 and TRIM15. The top biological pathways implicated by IgG autoantibodies were mRNA processing and splicing while the top pathway implicated by IgA autoantibodies was double-stranded DNA break repair via homologous recombination.
Conclusion
Proteome-wide autoantibody profiling in LN revealed both canonical and novel antigenic targets across IgG, IgA, and IgM classes. Many novel proteins are associated with immune-relevant pathways, while others are uncharacterized, offering new insights into disease mechanisms and potential biomarkers.