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<p>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.</p>

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Altered B cell activation contributes to the immunopathogenesis of childhood arthritis-associated uveitis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月3日

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  • Bethany R. Jebson,
  • Benjamin Ingledow,
  • Vicky Alexiou,
  • Jakub Kubiak,
  • Persephone Jenkins,
  • Yuxuan Meng,
  • Melissa Kartawinata,
  • Restuadi Restuadi,
  • Wei-Yu Lin,
  • Chris Wallace,
  • Colin J. Chu,
  • Ameenat Lola Solebo,
  • Lucy R. Wedderburn,
  • Elizabeth C. Rosser,
  • Lucy R. Wedderburn,
  • Zoe Wanstall,
  • Fatjon Dekaj,
  • Aline Kimonyo,
  • Eileen Hahn,
  • Genevieve Gottschalk,
  • Freya Luling Feilding,
  • Alyssia McNeece,
  • Fatema Merali,
  • Elizabeth Ralph,
  • Emily Robinson,
  • Emma Sumner,
  • Andrew Dick,
  • Michael W. Beresford,
  • Emil Carlsson,
  • Joanna Fairlie,
  • Jenna F. Gritzfeld,
  • Oliver McClurg,
  • Karen Rafferty,
  • Athimalaipet V. Ramanan,
  • Teresa Duerr,
  • Michael Barnes,
  • Sandra Ng,
  • Kimme Hyrich,
  • Stephen Eyre,
  • Soumya Raychaudhuri,
  • Wendy Thomson,
  • John Bowes,
  • Jeronee Jennycloss,
  • Saskia Lawson-Tovey,
  • Paul Martin,
  • Andrew Morris,
  • Stephanie Shoop-Worrall,
  • Samantha Smith,
  • Michael Stadler,
  • Damian Tarasek,
  • Melissa Tordoff,
  • Annie Yarwood,
  • Wei-Yu Lin,
  • Prof Nophar Geifman,
  • Sarah Clarke

摘要

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+IgD-CD27- 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.