Clinical evaluation of a multiplexed protein panel to discriminate patients with psoriatic arthritis from those with rheumatoid arthritis. (#23)
Currently, the diagnosis of psoriatic arthritis (PsA)is based on the knowledge and expertise of the examining physician. One significant challenge they face is the overlapping clinical features of PsA with rheumatoid arthritis, osteoarthritis and other spondyloarthropathies. The development of a diagnostic test, which reliably distinguishes PsA from RA and other arthropathies would be of considerable clinical benefit. As a first step to the development of such a test, we evaluated the performance of a panel of candidate biomarker proteins, named PAPRICA, for its ability to discriminate between patients with PsA from those with RA. The PAPRICA assay is a multiplexed targeted proteomics (MRM) assay which includes 206 candidate biomarker proteins targeted by 423 peptides measured using reverse phase liquid chromatography coupled to triple quadrupole mass spectrometry (Agilent 1290 Infinity II chromatography system and 6495A QqQ). Peptide peaks in the assay were quantified using Skyline (v.220.127.116.1117) and data analysed by both univariate and multivariate statistical methods. Evaluation of the analytical performance revealed highly reproducible peptide separations (mean retention time %CV=0.1%)and quantification (mean peak area %CV of less than 9%) for all proteins. Application of the PAPRICA assay to PsA (n=94) and RA (n=72) samples and subsequent Random Forest analysis revealed an AUC of 0.90 and an overall accuracy of 83%. Of the 94 PsA patients, the PAPRICA assay suggested 9 may have RA and of the 72 RA patients that 19 may have PsA. Further examination of the clinical presentation of these patients will help establish the authenticity of the PAPRICA data. These findings demonstrate the ability of the PAPRICA method to discriminate patients with PsA from those with RA. In ongoing studies, the method will be validated by applying it to additional cohorts of PsA and RA patients.