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Kidney Week

Abstract: TH-PO0709

Immunoproteomic Landscape of Lupus Nephritis: Identifying Novel Biomarkers Across Cellular Subtypes

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Yang, Bowen, University of Houston, Houston, Texas, United States
  • Zhang, Shu, University of Houston, Houston, Texas, United States
  • Xiao, Min, University of Houston, Houston, Texas, United States
  • Tang, Chenling, University of Houston, Houston, Texas, United States
  • Ostadnejad, Neda, University of Houston, Houston, Texas, United States
  • Teymur, Aygun Aya, University of Houston, Houston, Texas, United States
  • Saxena, Ramesh, The University of Texas at Dallas, Richardson, Texas, United States
  • Mohan, Chandra, University of Houston, Houston, Texas, United States
  • Jung, Sung Yun, Baylor College of Medicine, Houston, Texas, United States
  • Wu, Tianfu, University of Houston, Houston, Texas, United States

Group or Team Name

  • University of Houston Biomedical Engineering Department: Wu Lab.
Background

Lupus nephritis (LN), a frequent and serious complication of systemic lupus erythematosus (SLE), can progress to kidney failure. While existing autoantibody (AAb) tests provide some clinical utility in LN, their sensitivity and specificity remain suboptimal. This study aimed to identify novel autoantibodies with improved diagnostic and disease-monitoring potential for LN.

Methods

This study examined autoantibody profiles of subjects by applying immunoproteomics to 5 cell lines, modeling aspects of LN through renal cells and a variety of immune cells. Candidate AAbs were screened through literature and String analysis for novelty and relevance to LN. We validated top candidate AAbs using a multiplex, high-throughput microwell array in a 96-well format. The relationship between these potential biomarkers and measures of disease state were examined via Mann-Whitney U test, ROC curve analysis, Spearman correlation and linear regression.

Results

We identified 691 potential autoantigens via immunoproteomics. We attempted to validate 14 of these targets. We were able to identify anti-HYOU1 IgG, anti-S100A2 IgG, anti-ACLY IgG, anti-PDIA3 IgG and anti-HPGD IgG as candidate AAb biomarkers in LN. Anti-HYOU1 IgG particularly stood out and serum concentrations of HYOU1 were also examined. Both anti-HYOU1 and HYOU1 correlated with clinical measures of LN severity and showed potential as new biomarkers for LN.

Conclusion

Through immunoproteomic screening, we were able to identify several new AAb biomarkers of LN derived from various cell types. Anti-HYOU1 and HYOU1 showed great potential as new biomarkers for LN.

 anti-HPGD IgGanti-S100A2 IgGanti-ACLY IgGanti-PDIA3 IgGanti-HYOU1 IgG
AUC of ROC0.64490.73230.66670.65090.7456
p-value0.0940.00590.00050.0021<0.0001
Positivity34.78%67.39%58.42%65.71%57.58%
Cutoff> 4.977> 20.14> 16.43> 19.47> 24.48

Funding

  • Other NIH Support

Digital Object Identifier (DOI)