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

Larger studies may also help in revealing clinically-useful biomarkers. Risk factors such as young age and presence of ANA, assumed to reflect aberrant immune activation, 37, 40, 64, 71 indicate patients potentially at higher risk of uveitis but are in no way predictive of disease outcome. An easily-testable biomarker such as a genotype would be highly impactful in the management of uveitis, as it would help in overcoming the challenge of detecting the insidious onset of disease 7, 48, 65 . Intriguingly, after deeper examination of the phenotypic data, we found that 99% of female uveitis cases in our study carry at least one copy of the variant coding for serine-11. The only female uveitis case who did not carry serine-11 in HLA-DRB1 appeared to suffer from ANA-negative oligoarthritis with mild vitritis and peripheral multifocal choroiditis in the absence of anterior segment inflammation; this ocular finding is atypical for JIA, and thus, according to our inclusion criteria, this sample was likely improperly included at cohort collection. Prospective studies in larger populations, including detailed clinical evaluation of development of uveitis and secondary uveitis phenotypes, will be necessary to dissect the potential of serine-11 or other genotypes as biomarkers for disease risk. Regardless, the current study justifies further genetic analysis as a potentially powerful instrument in moving analysis of the genetic architecture of uveitis towards accurate and efficient clinical decision tools.