Analysis of DNA Methylation in Spondyloarthritis — METYLAS  

Axial Spondyloarthritis Clinical Trial

Official title: Analysis of DNA Methylation in Spondyloarthritis

Status Completed

Clinical Trial Summary

The aim of this project is to quantify global DNA methylation in patients with Ankylosing Spondylitis or Axial Spondyloarthritis as compared with control subjects.

Clinical Trial Description

Spondyloarthritis covers a group of diseases with common clinical, genetic and radiographic characteristics. Ankylosing spondylitis (AS) is the most common of these, and is usually diagnosed in the presence of bilateral sacroiliitis by conventional x-ray, according to the modified New York criteria. Axial spondyloarthritis (Ax-SpA) mainly affects the axial skeleton and progresses towards the formation of bone or bony structures around the sacro-iliac joint and spine, leading to the gradual formation of a bony bridge from the sacro-iliac joint and ligamentous ossifications to the spine. Early forms of the disease do not present such modifications to the sacro-iliac joint and therefore, show no visible sacroiliitis on conventional x-ray. Thus, it is possible to classify a patient aged <45 years with inflammatory lower back pain as having Ax-SpA, irrespective of the presence of sacroiliitis by x-ray. Indeed, inflammation of the sacro-iliac joint and spine occurs before the process of ossification and inflammation, and can be detected by MRI. This led the Assessment of SpondyloArthritis international Society (ASAS) group to propose candidate classification criteria for Ax-SpA, notably adapted to early forms of the disease. Accordingly, patients with Ax-SpA without radiographic sacroiliitis are considered to have non-radiographic Ax-SpA. Classification criteria for peripheral SpA are also available. The determinants of AS and SpA are complex, and involve both genetic and environmental factors. In addition to these factors, several studies in recent years have also highlighted the emerging role of epigenetics in the pathophysiology of inflammatory diseases. The term epigenetics refers to heritable and reversible modifications in gene expression without any change in the coding DNA sequence. This process may be involved in the pathophysiology of different diseases and their clinical expression. Several different epigenetic mechanisms may concur to modify gene functioning. Changes to the chromatin and to DNA (without modification of the encoding sequence itself) have been shown to be important for the control of gene expression through suppressive or permissive factors. Thus, DNA methylation could play a role in auto-immune or inflammatory diseases by regulating gene expression, particularly those coding for pro-inflammatory mediators such as certain cytokines, thereby contributing to dysregulation of the immune system. DNA methylation is regulated by the activity of DNA methyltransferase enzymes (DNMT). In multicellular eukaryotic organisms, DNA methylation is associated with chromatin repression, and thereby, inhibition of gene expression. DNA methylation can be evaluated across the whole genome, but also at the level of a specific candidate gene, such as the gene encoding a pro-inflammatory cytokine. The level of DNA methylation has been evaluated in rheumatoid arthritis (RA) and in systemic lupus erythematosus (SLE), and a "methylated-DNA" signature has been observed in these auto-immune diseases. Currently, there is no available data regarding DNA methylation in AS or SpA in general. In this study, the investigators aim to analyse the global DNA methylation in patients with AS or Ax-SpA. ;

Related Conditions & MeSH terms

• Axial Spondyloarthritis
• DNA Methylation
• Spondylarthritis
• Spondylitis
• Spondylitis, Ankylosing

• NCT number: NCT03092583
• Study type: Interventional
• Source: Centre Hospitalier Universitaire de Besancon
• Status: Completed
• Phase: N/A
• Start date: February 15, 2017
• Completion date: October 7, 2020