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

Heinrike Schmeling; Jens Klotsche; Babatope O Adebiyi; Frank Dressler; Dirk Foell; Ivan Foeldvari; Johannes-Peter Haas; Arnd Heiligenhaus; Gerd Horneff; Anton Hospach; Tilmann Kallinich; Jasmin Kuemmerle-Deschner; Kirsten Moenkemoeller; Prasad T Oommen; Christiane Reiser; Frank Weller-Heinemann; Daniel Windschall; Marvin J Fritzler; Kirsten Minden

doi:10.1186/s13075-026-03835-5

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

Arthritis Res Ther. 2026 May 26. doi: 10.1186/s13075-026-03835-5. Online ahead of print.

Authors

Heinrike Schmeling^{1

2

3

4}, Jens Klotsche⁵, Babatope O Adebiyi⁶, Frank Dressler⁷, Dirk Foell⁸, Ivan Foeldvari⁹, Johannes-Peter Haas¹⁰, Arnd Heiligenhaus¹¹, Gerd Horneff^{12

13}, Anton Hospach¹⁴, Tilmann Kallinich^{5

15

16}, Jasmin Kuemmerle-Deschner¹⁷, Kirsten Moenkemoeller¹⁸, Prasad T Oommen¹⁹, Christiane Reiser^{17

20}, Frank Weller-Heinemann²¹, Daniel Windschall²², Marvin J Fritzler²³, Kirsten Minden^{5

15

16}

Affiliations

¹ Section of Rheumatology, Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. heinrike.schmeling@albertahealthservices.ca.
² Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. heinrike.schmeling@albertahealthservices.ca.
³ McCaig Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. heinrike.schmeling@albertahealthservices.ca.
⁴ Section of Rheumatology, Alberta Children's Hospital, Calgary, AB, Canada. heinrike.schmeling@albertahealthservices.ca.
⁵ Deutsches Rheuma-Forschungszentrum Berlin, Leibniz Institute, Program area Epidemiology and Health Services Research, Berlin, Germany.
⁶ Section of Rheumatology, Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
⁷ Hannover Medical School, Children's Hospital, Hannover, Germany.
⁸ Department of Pediatric Rheumatology and Immunology, University of Münster, Münster, Germany.
⁹ Hamburg Centre for Pediatric and Adolescent Rheumatology, Hamburg, Germany.
¹⁰ German Center for Pediatric and Adolescent Rheumatology, Garmisch-Partenkirchen, Germany.
¹¹ Department of Ophthalmology, St Franziskus Hospital, University of Duisburg-Essen, Münster, Germany.
¹² Department of General Paediatrics, Asklepios Clinic Sankt Augustin, Sankt Augustin, Germany.
¹³ Department of Paediatrics and Adolescent Medicine, University Hospital of Cologne, Cologne, Germany.
¹⁴ Klinikum Stuttgart Olgahospital, Stuttgart, Germany.
¹⁵ Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
¹⁶ German Center for Child and Adolescent Health (DZKJ), partner site Berlin, Berlin, Germany.
¹⁷ University of Tuebingen Hospital, Tuebingen, Germany.
¹⁸ Department of Pediatrics, Kinderkrankenhaus Amsterdamer Straße, Cologne, Germany.
¹⁹ Division of Pediatric Rheumatology, Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
²⁰ Pediatric Rheumatology, Department of Pediatrics, Landeskrankenhaus Bregenz, Bregenz, Austria.
²¹ Professor Hess Children's Hospital, Bremen, Germany.
²² Medical Faculty, St. Josef Stift, Sendenhorst, University of Halle-Wittenberg, Halle, Germany.
²³ McCaig Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

PMID: 42192482
DOI: 10.1186/s13075-026-03835-5

Abstract

Objective: To identify serum biomarkers associated with the development of uveitis in a German juvenile idiopathic arthritis (JIA) cohort.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: ANA pattern; ANA titers; Anti-PFDN5; Biomarker; Juvenile idiopathic arthritis; Uveitis.

Abstract

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