BACKGROUND: Proteomic approaches are central in biomarker discovery. While mass-spectrometry-based techniques are widely used, novel targeted proteomic platforms have enabled the high-throughput detection of low-abundance proteins in an affinity-based manner. Urine has gained growing attention as an ideal biofluid for monitoring renal disease including lupus nephritis (LN). METHODS: Pubmed was screened for targeted proteomic studies of LN urine interrogating ≥1000 proteins. Data from the primary studies were combined and a meta-analysis was performed. Shared proteins elevated in active LN across studies were identified, and relevant pathways were elucidated using ingenuity pathway and gene ontology analysis. Urine proteomic data was cross-referenced against renal single-cell RNAseq data from LN kidneys. RESULTS: Two high-throughput targeted proteomic platforms with capacity to interrogate ≥1000 proteins have been used to investigate LN urine. Twenty-three urine proteins were significantly elevated in both studies, including 10 chemokines, and proteins implicated in angiogenesis, and extracellular matrix turnover. Of these, Cathepsin S, CXCL10, FasL, ferritin, macrophage migration inhibitory factor (MIF), and resistin were also significantly elevated within LN kidneys. CONCLUSION: Targeted urinary proteomics have uncovered multiple novel biomarkers for LN. Further validation in prospective cohorts and mechanistic studies are warranted to establish their clinical utility.
BACKGROUND: Proteomic approaches are central in biomarker discovery. While mass-spectrometry-based techniques are widely used, novel targeted proteomic platforms have enabled the high-throughput detection of low-abundance proteins in an affinity-based manner. Urine has gained growing attention as an ideal biofluid for monitoring renal disease including lupus nephritis (LN). METHODS: Pubmed was screened for targeted proteomic studies of LN urine interrogating ≥1000 proteins. Data from the primary studies were combined and a meta-analysis was performed. Shared proteins elevated in active LN across studies were identified, and relevant pathways were elucidated using ingenuity pathway and gene ontology analysis. Urine proteomic data was cross-referenced against renal single-cell RNAseq data from LN kidneys. RESULTS: Two high-throughput targeted proteomic platforms with capacity to interrogate ≥1000 proteins have been used to investigate LN urine. Twenty-three urine proteins were significantly elevated in both studies, including 10 chemokines, and proteins implicated in angiogenesis, and extracellular matrix turnover. Of these, Cathepsin S, CXCL10, FasL, ferritin, macrophage migration inhibitory factor (MIF), and resistin were also significantly elevated within LN kidneys. CONCLUSION: Targeted urinary proteomics have uncovered multiple novel biomarkers for LN. Further validation in prospective cohorts and mechanistic studies are warranted to establish their clinical utility.
Authors: Andrea Fava; Deepak A Rao; Chandra Mohan; Ting Zhang; Avi Rosenberg; Paride Fenaroli; H Michael Belmont; Peter Izmirly; Robert Clancy; Jose Monroy Trujillo; Derek Fine; Arnon Arazi; Celine C Berthier; Anne Davidson; Judith A James; Betty Diamond; Nir Hacohen; David Wofsy; Soumya Raychaudhuri; William Apruzzese; Jill Buyon; Michelle Petri Journal: Arthritis Rheumatol Date: 2022-04-16 Impact factor: 15.483