Urine proteomics by mass spectrometry identifies proteins involved in key pathogenic pathways in patients with juvenile dermatomyositis

• Published in: Rheumatology (Oxford, England) Vol. 62; no. 9; pp. 3161 - 3168
• Main Authors: Morales, Melissa, Alayi, Tchilabalo D, Tawalbeh, Shefa M, Sydenstricker, Agnes V, Spathis, Rita, Kim, Hanna, Nagaraju, Kanneboyina, Hathout, Yetrib, Rider, Lisa G
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-09-2023
• Subjects: Basic Science; Cathepsin D; Child; Dermatomyositis; Humans; Mass Spectrometry; Myositis; Proteomics; JDM; urine proteomics; cathepsin D; galectin-3 binding protein; tandem mass tag labelling; myositis
• ISSN: 1462-0324; 1462-0332; 1462-0332
• DOI: 10.1093/rheumatology/kead033

Abstract
Objectives
To identify and validate biomarkers in JDM patients using a multiplexing tandem mass tag urine proteome profiling approach.
Methods
First morning void urine samples were collected from JDM patients (n = 20) and healthy control subjects (n = 21) and processed for analysis using a standardized liquid chromatography-tandem mass spectrometry approach. Biomarkers with significantly altered levels were correlated with clinical measures of myositis disease activity and damage. A subset of candidate biomarkers was validated using commercially available ELISA kits.
Results
In total, 2348 proteins were detected in the samples, with 275 proteins quantified across all samples. Among the differentially altered proteins, cathepsin D and galectin-3 binding protein were significantly increased in the urine of JDM patients (adjusted P < 0.05), supporting previous findings in myositis patients. These two candidate biomarkers were confirmed with ELISAs. Cathepsin D positively correlated with Myositis Damage Index (r = 0.57, P < 0.05) and negatively correlated with the Childhood Myositis Assessment Scale (r = −0.54, P < 0.05). We also identified novel JDM candidate biomarkers involved with key features of myositis, including extracellular matrix remodelling proteins.
Conclusion
This study confirmed the presence of several proteins in the urine of JDM patients that were previously found to be elevated in the blood of myositis patients and identified novel candidate biomarkers that require validation. These results support the use of urine as a source for biomarker development in JDM.