Targeted urine proteomics in lupus nephritis – a meta-analysis

ABSTRACT

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.

KEYWORDS:

• Urine biomarkers
• proteomics
• lupus nephritis
• chemokines
• pathogenesis

Author contributions

C. Mohan designed the study. V. Duran, T. Zhang, and K. Vanarsa performed the analysis. T. Zhang and C. Mohan drafted and revised the manuscript. All authors approved the final version of the manuscript.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplemental data

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was supported in part by funding from the NIH (R01 AR074096).