An amino acid motif in HLA-DRß1 distinguishes patients with uveitis in juvenile idiopathic arthritis

A.J.W. Haasnoot; M.W. Schilham; S.S.M. Kamphuis; P.C.E. Hissink Muller; A. Heiligenhaus; D. Foell; R.A. Ophoff; T.R.D.J. Radstake; A.I. Den Hollander; T.H.C.M. Reinards; S. Hiddingh; N. Schalij-Delfos; E.P.A.H. Hoppenreijs; M.A.J. van Rossum; C. Wouters; R.K. Saurenmann; N. Wulffraat; R. ten Cate; J.H. de Boer; S.L. Pulit; J.J.W. Kuiper

While much progress has been made in understanding the biology of JIA, 16,20 our understanding of the genetic landscape of uveitis is more limited. Only a handful of candidate gene studies 41 and HLA-specific analyses 4,17-19 have investigated uveitis as a phenotype separate from all JIA. A recent GWAS identified HLA-DRB1*1501 as a risk factor for uveitis, 67 and recent studies in JIA-associated uveitis point toward a role for infiltrated plasma cells 68 , T helper cells 4 , and changes in the ocular fluid microenvironment. 43, 69, 70 Future, larger genetic studies comparing JIA-uveitis and JIA without uveitis, with and without sex-specific analysis, will likely expand our understanding of uveitis pathogenesis in a number of ways. Broad case inclusion will elucidate whether subtype-specific architectures exist and larger samples will improve statistical power to identify more modest-effect disease-modifying variants both within and outside of the MHC. For example, this may substantiate the association of additional HLA alleles (such as HLA-DPB1) with uveitis in JIA (Figure 1) .