Early biomarkers of joint damage in rheumatoid and psoriatic arthritis.

Angela Mc Ardle,Stephen R Pennington,Brian Flatley,Oliver Fitzgerald

doi:10.1186/s13075-015-0652-z

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.

Highlights

Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are the most prevalent forms of inflammatory arthritis affecting ~1 % and ~ 0.3 to 1 % of the population, respectively [1, 2]
In relation to what has been shown to date, considerably more candidate biomarkers have been identified in RA compared with PsA (Table 2)
No single biomarker has been validated as a potent predictor of joint damage and it is well recognised that a multi-biomarker panel is needed to compensate for the heterogeneity between individuals

Summary

Introduction

Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are the most prevalent forms of inflammatory arthritis affecting ~1 % and ~ 0.3 to 1 % of the population, respectively [1, 2]. The onset of RA and PsA is clinically recognised when a patient presents with symptoms fulfilling disease classification criteria, importantly the American College of Rheumatology criteria for RA and. Increased straight, branching vascularisation is a prominent feature observed in RA joints, whereas the formation of elongated, bushy, torturous blood vessels is a more marked feature of the PsA joint [8, 9]. In the RA joint there is increased macrophage infiltration and subsequent synovial invasion compared with that observed in PsA. It has been reported that the extent of T-cell and B-cell infiltration is comparable in both conditions and the formation of germinal centres (zones of T-cell and B-cell proliferation) are observed in both PsA and RA joints [8, 10, 11].

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