Identification and Evaluation of Serum Protein Biomarkers That Differentiate Psoriatic Arthritis From Rheumatoid Arthritis

Abstract

Objective. To identify serum protein biomarkers that might distinguish patients with early inflammatory arthritis (IA) with psoriatic arthritis (PsA) from those with rheumatoid arthritis (RA) and may be used to support appropriate early intervention.Methods. The serum proteome of patients with PsA and patients with RA was interrogated using nano-liquid chromatography mass spectrometry (nano-LC-MS/MS) (n = 64 patients), an aptamer-based assay (SomaScan) targeting 1,129 proteins (n = 36 patients), and a multiplexed antibody assay (Luminex) for 48 proteins (n = 64 patients). Multiple reaction monitoring (MRM) assays were developed to evaluate the performance of putative markers using the discovery cohort (n = 60 patients) and subsequently an independent cohort of PsA and RA patients (n = 167).Results. Multivariate machine learning analysis of the protein discovery data from the 3 platforms revealed that it was possible to differentiate PsA patients from RA patients with an area under the curve (AUC) of 0.94 for nano-LC-MS/MS, 0.69 for bead-based immunoassay measurements, and 0.73 for aptamer-based analysis. Subsequently, in the separate verification and evaluation studies, random forest models revealed that a subset of proteins measured by MRM could differentiate PsA and RA patients with AUCs of 0.79 and 0.85, respectively.Conclusion. We present a serum protein biomarker panel that can separate patients with early-onset IA with PsA from those with RA. With continued evaluation and refinement using additional and larger patient cohorts, including those with other arthropathies, we suggest that the panel identified here could contribute to improved clinical decision making.

Harnessing Big Data, Smart and Digital Technologies and Artificial Intelligence for Preventing, Early Intercepting, Managing, and Treating Psoriatic Arthritis: Insights From a Systematic Review of the Literature

“…Mc Ardle et al. ( 31 ) coupled cutting-edge serum proteomics with multivariate machine learning analyses to differentiate between patients suffering from psoriatic arthritis and those with rheumatoid arthritis. Different proteomics techniques were utilized: namely, nano-liquid chromatography mass spectrometry, SomaScan, an aptamer-based assays, and Luminex, a multiplexed antibody assay.…”

Omics and Multi-Omics Analysis for the Early Identification and Improved Outcome of Patients with Psoriatic Arthritis

“…Proteomics can be defined as the large-scale analysis of proteins. In the context of PsA, it has been applied mainly to identify biomarkers that can be detected in blood, synovial fluid or skin samples for the early diagnosis of PsA and its differentiation from psoriasis [ 47 , 48 , 49 ]. The proteome is much more complex and dynamic than the genome because there are an estimated ~20,000 protein-encoding genes in the human genome [ 50 ], but these give rise to multiple variants by alternative transcription, splicing and processing of RNA, post-translational modification and protein–protein interactions.…”

“…Most of the biomarker candidates are proposed for the detection of PsA [ 61 , 62 ], differentiation between mild and severe forms [ 63 , 64 ], measuring disease activity [ 65 ], or predicting which psoriasis patients are likely to develop PsA [ 66 ]. However, others have been proposed to distinguish PsA from other arthritic diseases such as RA [ 49 , 67 ] or to monitor responses to therapy [ 68 , 69 , 70 , 71 ]. For example, the label-free MS analysis of synovial fluid from PsA patients revealed 12 candidate PsA markers including the injury marker MMP3, as well as the inflammatory proteins S100A9 and CRP [ 62 ].…”

Serum leucine-rich alpha-2 glycoprotein levels in rheumatoid arthritis and spondyloarthritis: A promising biomarker

“…This increase in LRG is associated with a relatively higher level of IL-6 in RA compared to SpA, which in turn produced a greater increase in LRG expression. 17 Nakajima et al, found that serum LRG levels were also elevated in patients with PsA compared to patients with psoriasis vulgaris. 23 Currently, there are no existing studies comparing LRG values in RA and SpA patients using blood samples.…”

“…By contrast, the administration of drugs targeting the interleukin (IL)-12/IL-23 and IL-17 pathways have proven beneficial in PsA, but not in RA. 17,18 In some cases, RA and SpA may show clinical symptoms that are difficult to distinguish from one another. Therefore, an examination to assist the diagnosis of RA and SpA is warranted.…”