Abstract: FR-PO853
Kidney Biopsy Proteome Reveals Novel Molecules and Pathways in Lupus Nephritis
Session Information
- Glomerular Diseases: Immunology, Inflammation - I
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Abu-Maziad, Asmaa Soliman, University of Arizona, Tucson, Arizona, United States
- Singh, Ram R., UCLA School of Medicine, Los Angeles, California, United States
Group or Team Name
- UCLA Autoimmunity and Tolerance Lab
Background
Lupus nephritis (LN) is a major cause of morbidity and mortality. Pathogenesis of LN is largely unclear. Identification of molecules that are differentially expressed between LN classes and normal control kidneys may help in elucidating mechanisms of LN and to help to identify potential new targets of treatment. Our objective in this study was to identify differences in specific proteins and molecular pathways between LN classes and normal kidneys. We hypothesized that morphologic changes that define the pathology of each class of lupus nephritis are characterized by specific protein expression.
Methods
Forty-eight formalin-fixed, paraffin embedded kidney biopsy specimens were obtained from UCLA Pathology repository. Kidney specimens included 10 histologically normal kidneys and 38 biopsy-proven LN by the 2003 International Society of Nephrology/Renal Pathology Society classification. These tissues were subjected to proteomics analysis using nano-scale liquid chromatography tandem mass spectroscopy (nLCMSMS) and tandom mass tag method for protein labeling. Quantitative relative expression data is extracted using Proteome Discoverer 2.2 Software. Ingenuity software was used for pathway analysis. Clinical and histological data were collected
Results
A total of 2190 peptides were identified in all 48 kidney specimens. Of the 2,190 peptides, 655 were differentially expressed between LN and normal control kidneys (FDR <0.05). Some of the top upregulated proteins included alpha-1-antichymotrypsin, keratin family proteins, immunoglobumins, alpha-1-antitrypsin, vimentin, and complements. The top downregulated proteins included apoptosis-inducing factor 1, glutathione S-transferase, V-type proton ATPase catalytic subunit A, transforming acidic coiled-coil-containing protein 3, and dipeptidase 1. Pathway analysis of differentially expressed peptides revealed a set of upregulated molecular pathways including immune cell communication, acute phase response signaling, glucocorticoid receptor signaling, and complement system, while pathways linked to oxidative phosphorylation, fatty acid oxidation, and amino acid degradation were reduced in LN compared to controls.
Conclusion
Using a relatively large cohort of LN kidney biopsies, we report a novel LN proteome using nLCMSMS. These data pave the way for defining molecular pathogenesis of LN and for identifying novel treatment targets