Abstract: FR-PO719

Proteomic Analysis of Renal Tissue in Lupus Nephritis

Session Information

Category: Glomerular

  • 1002 Glomerular: Basic/Experimental Pathology

Authors

  • Abu Maziad, Asmaa, Mattel Children's Hospital, UCLA, Los Angeles, California, United States
  • Singh, Ram R., UCLA School of Medicine, Los Angeles, California, United States
Background

Lupus nephritis (LN) occurs in 40-80% of children with systemic lupus erythematosus (SLE) and is a major cause of morbidity and mortality in childhood SLE. Pathogenesis of LN progression is unclear. Identification of molecules that are differentially expressed between early to late stages of LN may help in detecting the progression of kidney damage and to identify potential new targets of treatment.

Methods

This is a case-controlled study involving children and adolescents of 1-21 years of age who have biopsy-proven LN by the 2003 International Society of Nephrology/Renal Pathology Society classification. A total of 54 archived formalin-fixed and paraffin embedded kidney biopsy specimens obtained from UCLA Translational Pathology Core. These included 13 control specimens from transplanted kidneys with normal histology and 6-8 specimens for each of the six classes of LN. These tissues were subjected to proteomics analysis using nano-scale liquid chromatography tandem mass spectroscopy (nLCMSMS) by Tandom Mass Tag method for protein labeling. Quantitative relative expression data is extracted using Proteome Discoverer 2.0 Software. DAVID software was used for data analysis. Clinical /kidney biopsy data and outcomes were collected for both cohorts and entered in UCLA RedCap software.

Results

We have thus far completed the mass spectroscopy analysis of 22 kidney biopsies (2 class II, 2 class III, 5 class IV, 7 class V, 3 class VI, and 3 control), and identified a total of 2,000 proteins in the global analysis. Among these, 86 proteins were significantly different between control and LN specimens. Among the differentially expressed proteins, the following were upregulated: MHC Class I, LIM domain and actin binding 1, WD repeat domain 7, Rho GDP dissociation inhibitor beta, and cadherin 13. The significantly downregulated proteins included G protein subunit alpha i3, catenin beta 1, ubiquinol-cytochrome c reductase core protein I, heterogeneous nuclear ribonucleoprotein U-like 2, histone deacetylase 6, NFS1 cysteine desulfurase, and Thy-1 cell surface antigen. In-depth analyses of the data are in progress.

Conclusion

This preliminary work delineates proteins that are differentially expressed between control and LN kidneys. Ongoing work will complete the proteomic analyses of the remaining specimens, and perform pathway analyses of the controls and different classes of LN

Funding

  • Other NIH Support