Serological biomarkers of JIA-associated uveitis: ANA titers, ANA AC-30 staining pattern and prefoldin 5 antibodies

To identify serum biomarkers associated with the development of uveitis in a German juvenile idiopathic arthritis (JIA) cohort. A convenience sample, enriched for uveitis cases, was drawn from a prospectively followed inception cohort of newly diagnosed JIA patients (ICON). Baseline serum samples were biobanked, and each was tested for conventional and novel autoantibodies using multi-analyte array technologies. Associations between uveitis occurrence, disease outcomes, and autoantibody profiles were examined. Fifty-two patients with and 141 patients without uveitis were included in the analyses. At first uveitis documentation, 26% of patients presented with uveitis-related complications. Younger age at JIA diagnosis, higher ANA titers (median [IQR]: 960 [240–5120] vs. 160 [0-640]; p < 0.001), and the Anti-Cell (AC-30) immunofluorescence (IIF) staining pattern (63.5% vs. 23.4%; p < 0.001) were significantly associated with the presence of uveitis, but not with uveitis-related complications. In contrast, the AC-4 IIF staining pattern was more often present in children without uveitis. In addition, patients with uveitis showed significantly higher prefoldin subunit 5 (PFDN5) antibody titers compared to non-uveitis JIA patients (mean ± SD; 486.39 ± 495.85 vs. 321.85 ± 330.36; p = 0.010). Other tested autoantibodies, including anti-histone antibodies, were rare in both groups and did not differ significantly. High ANA titers, the AC-30 ANA indirect immunofluorescence (IIF) pattern, and younger age at JIA onset are significantly associated with uveitis in JIA. Anti-PFDN5 antibodies show potential as a novel biomarker for JIA-associated uveitis. Combining these serological markers with clinical risk factors may improve early identification of high-risk patients and support the development of better tailored screening strategies to prevent vision-threatening complications. • High ANA titers and the AC-30 ANA IIF pattern are significantly associated with JIA-associated uveitis (JIA-U). • Prefoldin subunit 5 (PFDN5) antibodies show promise as a novel biomarker predicting JIA-U. • Combining serological markers with clinical risk factors improves early identification of high-risk patients.