The Acetyl Code in Rheumatoid Arthritis and Other Rheumatic Diseases

Abstract

Growing evidence supports the idea that aberrancies in epigenetic processes contribute to the onset and progression of human immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA). Epigenetic regulators of histone tail modifications play a role in chromatin accessibility and transcriptional responses to inflammatory stimuli. Among these, histone deacetylases (HDACs) regulate the acetylation status of histones and nonhistone proteins, essential for immune responses. Broad-spectrum HDAC inhibitors are well-known anti-inflammatory agents and reduce disease severity in animal models of arthritis; however, selective HDAC inhibitors remain poorly studied. In this review, we describe emerging findings regarding the aberrant acetyl code in RA and other rheumatic disorders which may help identify not only novel diagnostic and prognostic clinical biomarkers for RA, but also new targets for epigenetic pharmacological applications.

Keywords::

• histone deacetylases
• histone modifications
• rheumatoid arthritis

Financial & competing interests disclosure

KA Reedquist is supported by the Dutch Arthritis Association (NR 11–1–403); TR Radstake is supported by a grant from the European Research Council (ERC); DL Baeten is supported by a VICI grant from the Netherlands Scientific Organization (NWO) and a Consolidator grant from the ERC. They further declare a scientific and nonfinancial collaboration with Italfarmaco. The authors have no other 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 apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

KA Reedquist is supported by the Dutch Arthritis Association (NR 11–1–403); TR Radstake is supported by a grant from the European Research Council (ERC); DL Baeten is supported by a VICI grant from the Netherlands Scientific Organization (NWO) and a Consolidator grant from the ERC. They further declare a scientific and nonfinancial collaboration with Italfarmaco. The authors have no other 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 apart from those disclosed. No writing assistance was utilized in the production of this manuscript.