Serum Protein Biomarker Panel Differentiates Between Psoriatic Arthritis and Rheumatoid Arthritis

In patients with early inflammatory arthritis (EIA), a serum protein biomarker panel was proven effective in separating patients with psoriatic arthritis (PsA) from those with rheumatoid arthritis (RA), according to a study published in Arthritis and Rheumatology.1 This research is an important step in contributing towards improved clinical decision making.

“Early diagnosis and management of PsA leads to better long-term outcomes, however, with no diagnostic laboratory test available, the diagnosis is often delayed or missed, and this has significant consequences for individuals with PsA,” stated investigators. “At disease onset PsA often resembles other forms of arthritis including RA. Despite the clinical similarities between PsA and RA, their distinctive pathologies often require different treatments.”

For more information about psoriatic arthritis, view our Expert Perspective on the Management of Psoriatic Arthritis series.

While the ClASsification criteria for Psoriatic ARthritis (CASPAR) is highly sensitive and specific to classifying patients with PsA, it is not recommended for diagnosis, especially for those with early disease. Investigators posit that the ideal test would be based on biological samples, such as the serum or plasma in the blood. These samples are readily available and contain many proteins that can be used to spot potential PsA and RA cases. Nano-flow liquid chromatography mass spectrometry (nLC-MS/MS) are believed to be the most useful proteins in identifying differences between the 2 conditions.

During the analysis, serum proteome of patients analyzed nCL-MS/MS, an aptamer-based assay (SOMAscan) targeting 1129 proteins (36 patients), and a multiplexed antibody assay for 48 proteins (64 patients).

Investigators prioritized these proteins using multiple reaction monitoring (MRM), a highly versatile approach that can be easily developed and adapted to measure multiple proteins at the same time. The MRM was utilized in a 2-phase approach to analyze protein biomarkers identified in the nLC-MS/MS study. They first entered a verification phase to assess 150 biomarker proteins in the discovery cohort and used them to measure the proteins in that cohort. Next, they adapted the MRM assay to expand to a panel of 173 proteins and measured them in a separate independent cohort.

A total of 64 participants, 32 with RA and 32 with PsA, were used in the discovery and verification phase. Eligible patients had symptoms for less than 12 months, were treatment naïve with active joint inflammation, and aged 18 to 80 years. Patients met the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria. Baseline serum samples were obtained using standard methodology.

In the second verification phase, samples from 167 patients were used, with a total of 95 patients with PsA and 72 patients with RA. Baseline serum samples were obtained in this patient population as well. These confirmed the performance of putative markers identified in the first group.

A total of 451 proteins were identified, with 121 included in all 64 individual serum samples. A univariate analysis identified 175 proteins that were differentially expressed between PsA and RA patients, with a multivariate analysis indicating that PsA and RA could be differentiated with an area under the curve (AUC) of 0.73. This analysis was applied to the 121 commonly identified proteins and multivariate analysis was applied to this data, which showed 66 proteins being significantly differently in patients with PsA and RA.

These 3 platforms indicated that the protein data from PsA and RA patients could be discriminated with an AUC of 0.94 for nLC-MS/MS, 0.69 for bead-based immunoassay measurements, and 0.73 for aptamer-based analysis. MRM differentiated between the cohorts with AUCs of 0.79 for PsA and 0.85 for RA.

While the study was strengthened by the logical and comprehensive approach to biomarker development, the narrow amount of patient samples in both phases and the absence of a control group limits it. However, investigators believe that participants included in the study are representative of the average patient attending an inflammatory arthritis clinic.

“The work described herein represents a significant contribution towards the development of such a test. Fundamental next steps have been outlined and the MRM approach is ideally suited to support the large-scale studies required to develop and validate a robust panel of discriminatory biomarkers,” concluded investigators. “We believe with further development it will be possible to establish a diagnostic test for PsA which will reduce diagnostic delay, inform treatment selection, and improve both short-term and long-term outcomes.”

Reference:

Mc Ardle A, Kwasnik A, Szenpetery A, et al. Identification and Evaluation of Serum Protein Biomarkers Which Differentiate Psoriatic from Rheumatoid Arthritis [published online ahead of print, 2021 Jun 11]. Arthritis Rheumatol. 2021;10.1002/art.41899. doi:10.1002/art.41899