HLA-DR, DQ Class II DNA Typing in Pediatric Panuveitis and Tubulointerstitial Nephritis and Uveitis (TINU) – Accepted Manuscript

Abstract: Purpose: To describe chorioretinal lesions in pediatric uveitis that are strongly associated with the HLA-DR,DQ Class II type associated with tubulointerstitial nephritis and uveitis (TINU).Design: Retrospective, observational case series.Methods: Results: Fourteen of the 15 patients (93%) with otherwise unexplained pediatric panuveitis typed HLA-DRB1*01-HLA-DQB1*05. Eleven of 15 (73.3%) had bilateral sharply demarcated, usually inferior, 200-300 micron spots of chorioretinal atrophy, and 4 of 15 (27.7%) had bilateral clusters of 500-750 micron poorly defined orange choroidal lesions without overlying atrophy of the retinal pigment epithelium. None had interstitial nephritis. Four of the 6 definite TINU cases had Class II typing and TINU risk alleles; all 6 had bilateral panuveitis. The frequency of risk alleles was statistically higher in pediatric panuveitis than in the North American population, and in non-panuveitis pediatric uveitis patients assumed to have the North American HLA distribution (P<.0001, Fischer’s Exact). Positive likelihood ratios were 9.92 to 5.18 depending on assumptions regarding pre-test probability of disease.Conclusions: Recognition of characteristic chorioretinal lesions in otherwise unexplained pediatric panuveitis, supported by selective HLA Class II DNA typing, is useful in narrowing diagnostic possibilities and directing further evaluations. Panuveitis is under appreciated as a manifestation of TINU.