Analysis of DNA Methylation in Spondyloarthritis
Condition: Spondylitis, Ankylosing; Axial Spondyloarthritis; DNA Methylation
MeSH terms: Spondylitis; Spondylarthritis; Axial Spondyloarthritis; Spondylitis, Ankylosing
Study type: Interventional

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.
    

Detailed 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.
    

Intervention name(s): Blood sample
Intervention type(s): Other
Intervention description(s): 35 mL, 7 tubes
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science