Early biomarkers of joint damage in rheumatoid and psoriatic arthritis

Abstract

Joint destruction, as evidenced by radiographic findings, is a significant problem for patients suffering from rheumatoid arthritis and psoriatic arthritis. Inherently irreversible and frequently progressive, the process of joint damage begins at and even before the clinical onset of disease. However, rheumatoid and psoriatic arthropathies are heterogeneous in nature and not all patients progress to joint damage. It is therefore important to identify patients susceptible to joint destruction in order to initiate more aggressive treatment as soon as possible and thereby potentially prevent irreversible joint damage. At the same time, the high cost and potential side effects associated with aggressive treatment mean it is also important not to over treat patients and especially those who, even if left untreated, would not progress to joint destruction. It is therefore clear that a protein biomarker signature that could predict joint damage at an early stage would support more informed clinical decisions on the most appropriate treatment regimens for individual patients. Although many candidate biomarkers for rheumatoid and psoriatic arthritis have been reported in the literature, relatively few have reached clinical use and as a consequence the number of prognostic biomarkers used in rheumatology has remained relatively static for several years. It has become evident that a significant challenge in the transition of biomarker candidates to clinical diagnostic assays lies in the development of suitably robust biomarker assays, especially multiplexed assays, and their clinical validation in appropriate patient sample cohorts. Recent developments in mass spectrometry-based targeted quantitative protein measurements have transformed our ability to rapidly develop multiplexed protein biomarker assays. These advances are likely to have a significant impact on the validation of biomarkers in the future. In this review, we have comprehensively compiled a list of candidate biomarkers in rheumatoid and psoriatic arthritis, evaluated the evidence for their potential as biomarkers of bone (joint) damage, and outlined how mass spectrometry-based targeted and multiplexed measurement of candidate biomarker proteins is likely to accelerate their clinical validation and the development of clinical diagnostic tests.

Radiographic Progression According to Baseline C-reactive Protein Levels and Other Risk Factors in Psoriatic Arthritis Treated with Tofacitinib or Adalimumab

“…The magnitude of several risk factors at baseline, including mean CRP values, mTSS, erosion, and JSN scores was, however, generally lower in the OPAL Broaden patient population relative to other published randomized controlled trials that were designed to demonstrate superiority of active treatment relative to placebo, and in which structural progression was evaluated 17,18,19,20,21,22 . CRP, which is an acute-phase protein, reflects the systemic inflammation state and is believed to correlate with joint destruction in PsA 23 . Here, we show that tofacitinib and ADA substantially reduce mean levels of CRP in patients with PsA.…”

Biomarkers in rheumatic diseases: how can they facilitate diagnosis and assessment of disease activity?

“…7 36 Research groups have carried out broad scale multiplexed screens (simultaneous determination of several proteins in the same well using solid phase assays) and have identified about 20 cytokines and related mediators that are raised in rheumatoid arthritis. [37][38][39][40] An offshoot of these types of studies is the use of a novel commercially available protein biomarker panel (comprising vascular cell adhesion molecule 1 (VCAM-1), epidermal growth factor (EGF), vascular endothelial growth factor A (VEGF-A), IL-6 (interleukin 6), TNF receptor 1, MMP-1, MMP-3, YKL-40 (a secreted glycoprotein), leptin, resistin, serum amyloid A (SAA), and CRP) to monitor disease activity in rheumatoid arthritis. This panel incorporates various cytokines, chemokines, adhesion molecules, adipokines, and synovial or skeletal markers and has been shown to track disease activity in r heumatoid arthritis.…”

An MRM-Based Multiplexed Quantification Assay for Human Adipokines and Apolipoproteins

“…Thus, MRM facilitates the quantification of proteins over a wide dynamic range in a complex sample matrix such as human serum. Over the last decade, peptide-based MRM assays have been successfully applied for the detection and quantitation of biomarkers, for instance, for coronary artery diseases, different types of cancer, hypertension, arthritis, and intrauterine growth restriction [26,[32][33][34][35][36][37][38][39][40][41][42][43].…”