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Targeting the epigenetic modifications of synovial cells

  • Lars C. Huber
  • Astrid Jüngel
  • Steffen Gay
Part of the Progress in Inflammation Research book series (PIR)

Abstract

Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the synovial tissues of joints. As in other autoimmune-related disorders, neither the etiology nor the pathogenesis of RA has as yet been completely unraveled. It is generally accepted, however, that autoimmune disorders develop through a combination of the individual genetic susceptibility, environmental factors, and dysregulated immune responses. Genetic predisposition has been described in RA, in particular as “shared epitope”, a distinct sequence of amino acids within the antigen-presenting peptide groove of the major histocompatibility complex. Imbalanced immunity is reflected by the production of autoantibodies and the accumulation of reactive helper T cells within the rheumatoid synovium. In addition, environmental factors have been postulated as disease-modulating agents, including smoking, nutrition and infectious agents. So far, these factors have been studied almost exclusively as separate agents. However, gene transcription might be affected by ageing and environmental effects (such as nutrition and infections) — without changes in the nucleotide sequence of the underlying DNA. These patterns of alterations in the gene expression profiles are called “epigenetics”. The term epigenetics is used to refer to molecular processes that regulate gene expression patterns but without changing the DNA nucleotide sequence. These epigenetic changes comprise the post-synthetic methylation of DNA and post-transcriptional modifications of histones, including methylation, phosphorylation, ubiquitination, sumoylation, biotinlyation and, most importantly, deacetylation and acetylation. With respect to the complex pathogenesis of rheumatic diseases, the “epigenome” is an emerging concept that integrates different etiologies and, thus, offers the opportunity for novel therapeutic strategies. Based on the fact that current therapies have not resulted in an ACR70 above 60% and have never been targeting the activated synovial fibroblast, novel therapeutic strategies should target the epigenetic pathways of synovial activation in RA.

Keywords

Chronic Obstructive Pulmonary Disease Histone Modification HDAC Inhibitor Epigenetic Modification Synovial Fibroblast 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Birkhäuser Verlag Basel/Switzerland 2009

Authors and Affiliations

  • Lars C. Huber
    • 1
  • Astrid Jüngel
    • 1
  • Steffen Gay
    • 1
  1. 1.Center of Experimental Rheumatology, Department of RheumatologyUniversity Hospital of Zürich, Zürich Center of Integrative Human Physiology (ZIHP)ZürichSwitzerland

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