The fundamental process in JIA is chronic inflammation, in which the immune system understandably plays a critical role.[1] Both innate and adaptive immune systems have been implicated in the pathogenesis of various subtypes of JIA. Over the last two decades our understanding of the pathophysiology of this condition has

improved a great deal and several new genetic associations have been Selleck Ceritinib recognized.[1, 3, 4] Family studies have provided firm evidence for genetic susceptibility in JIA. Although many candidate genes have been tentatively identified, most of these lack validation studies on different populations and appropriate sample sizes.[1, 3, 4] Human leukocyte antigen (HLA) linkages have been noted in oligoarticular and polyarticular forms of

JIA. Oligoarticular JIA has been shown to be associated with HLA-A2, DR5 and DR8, whereas DRB1*04, DRB1*07 and DQA1*03 are said to be protective.[1, 3, 4] HLA-A2, DRB1*08, DQA1*04 and DPB1*03 are associated with RF-negative polyarticular JIA and DRB1*04, DQA1*03 and DQB1*03 with RF-positive polyarticular JIA. RF-positive polyarthritis is also associated with HLA-DR4, DR1 and DR14, whereas DQA1*02 is protective.[1, 3, 4] HLA associations for oligoarticular JIA and RF-negative polyarticular JIA overlap, selleck kinase inhibitor suggesting that these are genetically related. However, RF-positive polyarticular JIA appears to be a genetically distinct disorder and has HLA linkages similar to adult rheumatoid arthritis. Quite understandably, the clinical course, response to treatment and complications associated with RF-positive polyarticular JIA are also similar to adult rheumatoid arthritis. Several non-HLA genes

have now been discovered to be linked with subtypes of JIA and the list of putative markers has been expanding over the years. Although many such associations have been previously suggested, these have not been subsequently replicated in follow-up studies in different populations. Tyrosine-protein kinase BLK Independent confirmations could be obtained for only a few candidate genes like, such as ‘Protein tyrosine phosphatase, non-receptor type 22 (PTPN22)’, ‘Migration Inhibitory Factor (MIF)’, ‘Solute carrier 11 member 1 (SLC11A1)’ encoding for the natural resistance-associated macrophage protein 1, ‘WNT1 inducible signaling pathway protein 3 (WISP3)’ and ‘Tumour necrosis factor α gene (TNFA)’.[1, 3, 4] Thompson et al.[5] in a landmark study, examined a cohort of 809 JIA cases of non-Hispanic European ancestry and reported that ‘PTPN2’, ‘COG6’ and ‘ANGPT1’ were associated with oligoarticular and RF-negative polyarticular JIA. These are also known to be associated with type 1 diabetes mellitus, Crohn’s disease and multiple sclerosis, thus emphasizing the fact that common genetic mechanisms may underlie many autoimmune diseases and could influence therapeutic interventions.[5] In a subsequent study published in 2012, Thompson et al.