STUDIES ON ASSOCIATIONS OF ANTINUCLEAR ANTIBODIES WITH ANTIBODIES TO AN UVEITOGENIC PEPTIDE OF RETINAL S-ANTIGEN IN CHILDREN WITH UVEITIS

Objective. To determine if, in children with uveitis, antinuclear anti bodies (ANA) are associated with antibodies to an uveitogenic peptide of a soluble retinal antigen and to the homologous nuclear antigen, hi stone 3 (H3). ANA occur in most children with juvenile rheumatoid arth ritis (JRA) and associated uveitis. An uveitogenic segment of retinal soluble antigen (S antigen peptide) is homologous with a similarly uve itogenic peptide of H3. We investigated a possible association between ANA positivity, antibodies to H3, and antibodies to the uveitogenic S antigen peptide. Methods. The sera of 31 children with uveitis (20 of whom had associated JRA) were tested for the presence of ANA by indir ect immunofluorescence. Antibodies to H3 and to an uveitogenic peptide of S antigen (an 18 mer segment having the amino acid sequence DTNLAS STIIKEGIDKTV) were measured by enzyme immunoassay.Results. 19 of 20 ch ildren (95%) with JRA and associated uveitis and none of 11 with uveit is not associated with JRA had positive tests for ANA (X(2)=14.97; p<0 .00001). 16 of 19 ANA positive sera from subjects with JRA (84%) displ ayed reactivity with the chromosomal regions of metaphase cells. 9 of 20 patients with JRA with uveitis (45%) and 2 of 11 patients (18%) wit h uveitis not associated with JRA had antibodies to H3. Two uveitic pa tients with JRA (10%) and 2 non-JRA patients with uveitis (18%) reacte d with S antigen peptide. Antibodies to H3 occurred significantly more frequently in children with uveitis than in all adult control subject s (X(2)=12.98;p=0.003) and in adults with uveitis (X(2)=5.62; p=0.022) . Conclusion. Humoral immune responses to the uveitogenic peptide of S antigen and the homologous H3 antigen appear not to be uniquely impor tant in the immunopathology of uveitis associated with JRA. Antibodies to isolated H3 do not exclusively account for ANA positivity in the u veitic patient with JRA. A unique immunopathogenic mechanism for the d evelopment of uveitis associated with JRA is suggested by the observat ions that (1) children with uveitis associated with JRA are more likel y to be ANA positive than children with uveitis not associated with JR A, and (2) children with uveitis associated with JRA are significantly more likely to be ANA positive and to have antibodies to H3 than adul ts with uveitis.