Developing Biomarkers for Inflammatory Arthritis

This article originally appeared here.
Multiple peptide signatures were found to be significantly associated with each group.
Multiple peptide signatures were found to be significantly associated with each group.

Urinary proteomics may help identify biomarkers that can distinguish between different types of inflammatory arthritis, according to a study published in Scientific Reports.1

“Early diagnosis and treatment of chronic rheumatic conditions leads to improved clinical outcomes, but identifying and diagnosing these conditions is complex and often difficult, as there is no single diagnostic test for these conditions,” Stefan Siebert, MD, PhD, of the University of Glasgow in the United Kingdom, told Rheumatology Advisor.”

“New technologies, such as proteomics, offer opportunities to develop new tests to aid in diagnosis of inflammatory arthritis. However, most approaches use blood samples, the use of which is complicated by technical issues, particularly relating to the high circulating levels of albumin,” he said. “Urine proteomics, which measures peptide fragments in urine, does not have this problem and has been shown to have utility in a number of other conditions.” In addition, urine samples are easy to obtain and process in the primary care setting, where this type of testing is most needed.

Dr Siebert and colleagues used urine proteomics to identify novel biomarkers that differentiate between chronic arthropathy — including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and osteoarthritis (OA) — from inflammatory conditions, such as inflammatory bowel disease (IBD).

Each of the 5 study groups (RA, PsA, OA, IBD, and healthy controls) included 50 participants who were randomly assigned 2:1 to a training cohort or a validation cohort.

Among participants in the training cohort, multiple peptide signatures were found to be significantly associated with each group, ranging from 89 peptides in healthy controls to 566 in patients with RA.

The peptide signatures identified in the training cohort then underwent blinded testing in the validation cohort. “Unblinding revealed that these peptide signatures performed very well at differentiating the various conditions, suggesting that urine proteomics has potential as a method for developing biomarkers for inflammatory arthritis,” Dr Siebert concluded.

Summary and Clinical Applicability

Early identification and treatment of inflammatory arthritis leads to better outcomes, but this group of diseases is often challenging to diagnose. Using urinary proteomics, researchers identified biomarkers that reliably differentiated between several types of inflammatory arthritis, IBD, and healthy controls.

“Closer evaluation and pathway analysis of the peptides identified may also yield useful and potentially novel insights into the pathophysiology of these conditions,” Dr Siebert said. “We have highlighted some of the key peptides identified, but we have not evaluated this in more detail in our study due to the relatively small numbers.

Study Limitations

  • Because the validation cohort was small, the study results will require further validation in larger cohort
  • Some biomarkers could not be identified, possibly due to post-translational modifications

Disclosures

The sample collection and proteomics in this study were funded by an investigator-initiated competitive research grant from Pfizer to Dr Siebert. Dr Mischak is the co-founder and co-owner of Mosaiques Diagnostics and is employed by Mosaiques Diagnostics. Dr Latosinska is employed by Mosaiques Diagnostics.

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Reference

  1. Siebert S, Porter D, Paterson C, et al. Urinary proteomics can define distinct diagnostic inflammatory arthritis subgroups [published online January 16, 2017]. Sci Rep. 2017;7:40473. doi:10.1038/srep40473
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