Altered B cell activation contributes to the immunopathogenesis of childhood arthritis-associated uveitis
In Juvenile Idiopathic Arthritis (JIA), the most common childhood rheumatic disease, many patients also develop uveitis (JIA-uveitis), risking life-long vision loss. The mechanisms driving uveitis development in JIA remain understudied. Here, we demonstrate that peripheral blood CD19<sup>+</sup>IgD<sup>-</sup>CD27<sup>-</sup> double negative type 1 (DN1) B cells are elevated in JIA-uveitis compared to JIA patients without eye disease (JIA). The B cell receptor (BCR) repertoire was also more clonal and somatically hypermutated in JIA-uveitis and antigen-activated B cells infiltrated chronically inflamed JIA-uveitis eyes. Features of heightened B cell activation were recapitulated in experimental autoimmune uveoretinitis (EAU) and disrupting B and T cell interactions using monoclonal antibodies and transgenic mice suppresses uveitis. Together, these findings support a conceptual shift that uveitis is a primarily T cell driven disease and provide evidence for potential new therapeutic strategies that also consider B cells as drivers in disease pathology.
Authors
- Damian Tarasek
- Chris Wallace (ORCID: https://orcid.org/0000-0001-9755-1703)
- Persephone Jenkins
- Emily Robinson (ORCID: https://orcid.org/0000-0002-6692-5415)
- Annie Yarwood (ORCID: https://orcid.org/0000-0001-5026-9815)
- Bethany R. Jebson (ORCID: https://orcid.org/0000-0002-2794-8606)
- Elizabeth C. Rosser (ORCID: https://orcid.org/0000-0003-4800-4695)
- Emil Carlsson (ORCID: https://orcid.org/0000-0003-1266-5977)
- Fatema Merali
- Jenna F. Gritzfeld
- Ameenat Lola Solebo (ORCID: https://orcid.org/0000-0002-8933-5864)
- Nophar Geifman (ORCID: https://orcid.org/0000-0003-2956-6676)
- Teresa Duerr
- Elizabeth Ralph (ORCID: https://orcid.org/0000-0002-7955-7084)
- Zoe Wanstall
- Oliver McClurg
- Restuadi Restuadi (ORCID: https://orcid.org/0000-0001-8434-4465)
- Stephanie Shoop-Worrall (ORCID: https://orcid.org/0000-0002-9441-5535)
- Colin J. Chu (ORCID: https://orcid.org/0000-0003-2088-8310)
- Sandra Ng (ORCID: https://orcid.org/0000-0003-4524-6058)
- Jeronee Jennycloss
- Joanna Fairlie
- Benjamin Ingledow
- Stephen Eyre
- John Bowes
- Lucy R. Wedderburn
- Samantha Smith
- Andrew Morris
- Kimme Hyrich
- Vicky Alexiou
- Wendy Thomson
- Michael Barnes
- Sarah Clarke
- Jakub Kubiak
- Paul Martin
- Alyssia McNeece
- Emma Sumner
- Athimalaipet V. Ramanan
- Saskia Lawson-Tovey
- Wei-Yu Lin
- Karen Rafferty
- Melissa Tordoff
- Yuxuan Meng
- Michael Stadler
- Eileen Hahn
- Soumya Raychaudhuri
- Andrew Dick
- Aline Kimonyo
- Michael W. Beresford
- Melissa Kartawinata
- Fatjon Dekaj
Institutions
- Moorfields Eye Hospital NHS Foundation Trust (GB)
- University of Liverpool (GB)
- Queen Mary University of London (GB)
- University of Cambridge (GB)
- Great Ormond Street Hospital (GB)
- Great Ormond Street Hospital for Children NHS Foundation Trust (GB)
- University Hospitals Bristol NHS Foundation Trust (GB)
- University College of Osteopathy (GB)
- University of Surrey (GB)
- University of Manchester (GB)
- University of Bristol (GB)
- MRC Biostatistics Unit (GB)
- UCL Biomedical Research Centre (GB)
- MRC Epidemiology Unit (GB)
- University Hospitals Bristol and Weston NHS Foundation Trust (GB)
- University College London (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-02-03
- DOI
- https://doi.org/10.1038/s41467-025-68264-5
- Citations
- 1
- Primary Topic
- Ocular Diseases and Behçet’s Syndrome
- Type
- article
- Field-Weighted Citation Impact
- 22.55
Funders
- Wellcome Trust
- National Institute for Health and Care Research
- Lister Institute of Preventive Medicine
- Great Ormond Street Hospital Charity
- Ministerio de Economía y Competitividad
- Versus Arthritis
- Foundation for Research in Rheumatology
- Moorfields Eye Charity
- Medical Research Council
- NIHR Cambridge Biomedical Research Centre
- NIHR Great Ormond Street Hospital Biomedical Research Centre