THU0663 DO ANTIBODIES DIRECTED AGAINST HUMAN CILIARY BODY TISSUE PREDICT THE DEVELOPMENT OF UVEITIS IN JIA- A PRELIMINARY STUDY

Abstract

Background: Eleven -30% of Juvenile Idiopathic arthritis (JIA) children develop uveitis. JIA associated uveitis is completely asymptomatic and thus all children with oligo/extended oligo and polyarticular JIA require regular slit lamp examination by an ophthalmologist- a time consuming and distressing procedure particularly for small children. If not diagnosed early, or inadequately treated, it may lead to glaucoma, cataracts, persistent cystoid macular oedema and ultimately results in visual impairment and blindness. Whilst Anti- nuclear antibody positivity is found more commonly in those with uveitis, it is not sufficiently sensitive or specific as a screening tool. However the presence of these antibodies and the detection of B cells in the inflammatory infiltrate around the ciliary body in JIA Uveitis suggests a significant role for humeral mediated immune dysregulation in the pathogenesis of JIA Objectives: 1. Does the serum from Children with JIA associated uveitis contain antibodies directed against the ciliary body tissue of the human eye? 2. Could these be used to identify JIA patients at risk of developing uveitis? Methods: Whole human globe were formalin fixed paraffin embedded and 4um sections were obtained. Following blocking with Goat sera blocking, sections were incubated with JIA sera from children with and without uveitis (1:50 in PBT) for 1h. Secondary antibody (goat anti-human IgG-488).DAPI counterstaining was used Sections analysed by EE, using a Leica SP8 confocal microscope using LAS software. The operator was blinded to the status of the patient Results: Sera from 13 patients were analysed: 5 with uveitis and 8 with no uveitis. Six had oligo JIA; 3 extended Oligo; 4 Poly JIA. Four were ANA -ve; 8 ANA+ve Max titre1/80 (using HEp2 cells); 1 unknown. Treatment: Seven NSAID; 1 MTX; 2 MTX and Pred; 3 Biologics. 5 Topical steroids All tissue sections were analyzed blindly. Of the 5 patients with Uveitis 3 had antibodies against ciliary antigens and 2 did not. Of the 8 patients without uveitis 2 had antibodies against ciliary antigens and 6 did not. Fig 1 demonstrates immune histochemical findings from 2 typical patient's sera. No patient had high titres of antinuclear antibodies and there was no association between ANA positivity and ciliary body positivity. Fluorescent intensity was also higher in the Uveitis +ve patients Fig 2. Conclusion: This preliminary work suggests that antibodies to ciliary body proteins may be valuable in identifying patients with JIA at risk of developing uveitis with 60% of those with uveitis being antibody positive compared with only 25% of those without uveitis. Concurrent treatment may alter the presence of antibodies in the serum and may also have suppressed the development of uveitis in those patients who were antibody positive yet had not developed uveitis. Antibody patterning within the ciliary body may also provide further useful information. We are currently studying a further group of patients who have not received immunosuppressive drugs. (Figure Presented).