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Abstract: SA-PO659

Compartment Specific Analysis of Leukocyte Trans-Endothelial Migration Molecular Signature in IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1302 Glomerular Diseases: Immunology and Inflammation

Authors

  • Zhu, Fengge, Chinese PLA General Hospital, Beijing, Beijing, China
  • Chen, Xizhao, Chinese PLA General Hospital, Beijing, Beijing, China
  • Cai, Guangyan, Chinese PLA General Hospital, Beijing, Beijing, China
  • Chen, Xiangmei, Chinese PLA General Hospital, Beijing, Beijing, China
Background

The mechanism of how vascular lesions in IgA nephropathy affect renal disease progress remains unclear. Leukocyte trans-endothelium migration is an important bridge between blood vessels and tissue inflammation. This study analyzes the molecular signature of leukocyte trans-endothelial migration in IgA nephropathy based on the proteomic and the transcriptomic data of glomerulus, renal tubulointerstitium, peripheral blood mononuclear cells and peripheral CD14+ monocytes of IgA nephropathy.

Methods

The renal proteomic data are obtained from a local cohort of 59 IgA nephropathy patients and 19 healthy controls. RNA-seq transcriptomic data of glomerulus, renal tubulointerstitium, PBMCs and peripheral CD14+ monocytes in patients with IgA nephropathy are accessed from web based GEO database.

Results

1. Canonical molecules related to leukocyte trans-endothelial migration, including molecules in cell adhesion, anchoring and cell deformation are analyzed in IgA nephropathy kidneys. We find that MCAM, ICAM1 and CDH5 are significantly upregulated in IgA nephropathy compared to that of paracancerous tissue, and not in membranous nephropathy.
2. Pearson correlation analysis show that the leukocyte trans-endothelial migration molecular signature is not correlated with proteinuria, renal function, hypertension or serum complement level, but had a weak correlation with decreased S score in the Oxford classification.
3. One of the trans-endothelial migration related genes - Integrin α Subunit L (ITGAL) was significantly upregulated in the tubulointerstitium compartment of IgA nephropathy compared to healthy controls. However, there is no difference between IgA nephropathy and controls within the glomerulus, PBMCs, or peripheral CD14+ monocyte compartments.

Conclusion

The leukocyte trans-endothelial migration signature molecules are significantly upregulated in the renal tubulointerstitium of IgA nephropathy, but not in the glomerulus, PBMCs, or peripheral CD14+ monocytes. The leukocyte trans-endothelial migration signature is weakly correlated with decreased Oxford S score.