Assessing the potential of epigenetic targets as biomarkers in the diagnosis and treatment of rheumatoid arthritis

ABSTRACT

Introduction

Although there are gold-standard diagnostic guidelines and effective treatments to slow the disease progression of rheumatoid arthritis (RA), approximately 40% of patients still do not respond adequately to their initial treatment. The identification of specific and sensitive biomarkers for early and accurate diagnosis and response to treatment is a clinical priority and could reduce the time to effective therapy to mitigate the severity of tissue damage. Emerging studies show that epigenetic biomarkers play a role in RA-related pathways and are worthy targets that warrant further characterization.

Areas covered

In this review, the current significant literature around epigenetic studies of RA will be discussed, specifically, DNA methylation and histone modifications, being the most extensively studied. The pitfalls of biomarker studies in RA and how to potentially overcome barriers to their clinical application will be discussed.

Expert opinion

Epigenetic studies have shed light on mechanisms that mediate RA pathogenesis and potential roles as biomarkers of diagnosis and treatment response in conjunction with other biomarkers. Although these biomarkers are informative, limitations lie in their ease of use in clinical management and the requirement to ensure that the data are robust in large and diverse populations.

KEYWORDS:

• DNA methylation
• epigenetics
• histone modifications
• rheumatoid arthritis

Article highlights

• Early and accurate diagnosis of rheumatoid arthritis (RA) is difficult, and a significant minority of patients do not respond adequately to treatment; therefore, the identification of early biomarkers of diagnoses and response is a priority.

• Epigenetic factors have been gaining traction as attractive biomarkers of diagnosis and response to treatment in RA.

• DNA methylation signatures have been associated with RA susceptibility across disease-relevant tissues and cells as well as accessible tissue sources.

• Histone modifications mechanistically shed insight into transcriptional regulation of inflammatory genes in key cell types that drive RA pathology.

• DNA methylation has greater promise as a biomarker due to fewer technical challenges but require correlation with other additional and stable ‘omics and clinical marker.’

• Choice of cell type, appropriate outcome measures, modest effect and samples sizes, and replication of findings are continuing issues that require attention in this field.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This research was supported by Versus Arthritis and supported by the NIHR Manchester Biomedical Research Centre (NIHR203308). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.