Urinary proteomics can define distinct diagnostic inflammatory arthritis subgroups

Abstract

Current diagnostic tests applied to inflammatory arthritis lack the necessary specificity to appropriately categorise patients. There is a need for novel approaches to classify patients with these conditions. Herein we explored whether urinary proteomic biomarkers specific for different forms of arthritis (rheumatoid arthritis (RA), psoriatic arthritis (PsA), osteoarthritis (OA)) or chronic inflammatory conditions (inflammatory bowel disease (IBD)) can be identified. Fifty subjects per group with RA, PsA, OA or IBD and 50 healthy controls were included in the study. Two-thirds of these populations were randomly selected to serve as a training set, while the remaining one-third was reserved for validation. Sequential comparison of one group to the other four enabled identification of multiple urinary peptides significantly associated with discrete pathological conditions. Classifiers for the five groups were developed and subsequently tested blind in the validation test set. Upon unblinding, the classifiers demonstrated excellent performance, with an area under the curve between 0.90 and 0.97 per group. Identification of the peptide markers pointed to dysregulation of collagen synthesis and inflammation, but also novel inflammatory markers. We conclude that urinary peptide signatures can reliably differentiate between chronic arthropathies and inflammatory conditions with discrete pathogenesis.

Osteoarthritis biomarkers: year in review

“…Via mass spectrometry (MS), urinary peptides were sought which acted as diagnostic biomarkers for three common joint conditions (RA, PsA, OA) with healthy and inflammatory bowel disease control groups 62 . There were relatively low numbers (33 in each training group, 85 for validation).…”

Exploring the Psoriatic Arthritis Proteome in Search of Novel Biomarkers

“…In the context of PsA, urinary biomarkers may serve as novel classifiers for the differential diagnosis of inflammatory arthritides among which there is a lack of highly sensitive and specific diagnostic tests. Siebert et al attempted to address this clinical need by examining the proteomes of fifty RA, PsA, osteoarthritis (OA), or inflammatory bowel disease (IBD) patients and fifty healthy controls [ 34 ]. Using a capillary electrophoresis system coupled online to a MicroTOF (time-of-flight) mass spectrometer, they identified up to 566 peptides (RA) with 170 peptides being significantly associated with PsA compared to the other disease groups.…”

Proteomics in cardiovascular diseases: Unveiling sex and gender differences in the era of precision medicine

“…Another interesting biological fluid in proteomics is urine; similarly to plasma, it provides information not only from the urinary track, but also from other organs, potentially providing biomarkers for other systemic diseases. Moreover, urinary proteomics may be advantageous in terms of non-invasiveness of urine sampling, low dynamic range of analytes which facilitates the detection and analysis of biomarkers, lack of requirement for special sample preparation, and relative stability of the stored sample [82]. Of course, the interest in urinary proteome developed first in the field of urologic and kidney diseases, in particular in IgA nephropathy [83] and prostate cancer [84], but there is now an increasing interest in investigating urine as an orthogonal sample for studying systemic diseases [85].…”