A comprehensive review of the genetics of juvenile idiopathic arthritis

Juvenile idiopathic arthritis rers to a group of chronic arthropathies of childhood[1]. According to the International League of Associations for Rheumatology criteria, JIA comprises seven subtypes[2]. These include systemic JIA (sJIA), oligoarticular JIA, rheumatoid factor (RF)-negative polyarticular JIA, RF-positive polyarticular JIA, enthesitis related arthritis (ERA), psoriatic arthritis and undifferentiated JIA. The relatively homogeneous subtypes of JIA share clinical features with other chronic autoimmune disorders such as rheumatoid arthritis (RA), psoriasis or spondyloarthropathies [3]. Autoimmune disorders are relatively common in the population, estimated to have a prevalence of about ~5% in the US. While clinical and laboratory features distinguish many of these autoimmune disorders, there is accumulating evidence to support the hypothesis that clinically distinct autoimmune phenotypes share common genetic susceptibility factors. In this review, we will examine the genetic factors that underlie JIA susceptibility, and discuss some of the genetic factors that underlie multiple autoimmune phenotypes.All subtypes of JIA are characterized by persistent joint swelling caused by an accumulation of synovial fluid and thickening of the synovial lining. There is evidence to support the involvement of different components of the immune system in the etiopathogenesis of JIA. The synovial tissue contains various inflammatory cells including neutrophils, plasma cells, dendritic cells and a high proportion of activated T-cells [4-6]. The recruitment of pro-inflammatory cells into the synovium of a child with JIA is believed to be mediated by chemokines that selectively attract Th1 T-cells [7-9]. These T-cells are characterized by the production of interleukin (IL)-2, interferon-γ, and tumor necrosis factor (TNF)-β. Many other autoimmune disorders including RA, inflammatory bowel disease (IBD), psoriasis, and type 1 diabetes mellitus (T1DM) are also associated with Th1