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

A recent MHC fine-mapping study of the JIA categories tested here mapped the primary disease association signal to the G residue at position 13 in HLA-DRB1, and additionally identified an independent risk for serine at the same position. Analyzing all JIA patients (with and without uveitis), we also observed an association at glycine-13 (Supplementary Table 3 ). We sought to disentangle the previously-described association signal in all JIA (residues S or G at position 13) from the JIA-associated uveitis signal (residue S at position 11) observed here. We adjusted for either G or S at position 13 in the JIA-associated uveitis vs. non-uveitis JIA analysis and found the signal at serine-11 to be only moderately affected (serine-11 adjusted for glycine-13: OR = 2.41 [95% CI: 1.75 -3.32], p = 6.49 x 10 -8 ; adjusted for serine-13; OR = 2.61 [95% CI: 1.74 -3.93], p = 3.83 x 10 -6 ). These results indicate that the association signal in uveitis at serine-11 (or tyrosine-10 or threonine-12) cannot be fully explained by the JIA-associated amino acids in position 13 in HLA-DRB1.