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

Bethany R. Jebson; Benjamin Ingledow; Vicky Alexiou; Jakub Kubiak; Persephone Jenkins; Yuxuan Meng; Melissa Kartawinata; Restuadi Restuadi; Chris Wallace; Colin J. Chu; Ameenat Lola Solebo; 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

doi:10.1038/s41467-025-68264-5

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

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

Abstract

Abstract 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.

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Article Details

Journal Nature Communications

Volume / Issue Vol. 17, Issue 1

Published February 03, 2026

DOI 10.1038/s41467-025-68264-5

ISSN 2041-1723

Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio

ISSN: 2041-1723 Open Access Life Sciences

Authors (53)

B

Bethany R. Jebson

B

Benjamin Ingledow

V

Vicky Alexiou

J

Jakub Kubiak

P

Persephone Jenkins

Y

Yuxuan Meng

M

Melissa Kartawinata

R

Restuadi Restuadi

C

Chris Wallace

C

Colin J. Chu

A

Ameenat Lola Solebo

E

Elizabeth C. Rosser

L

Lucy R. Wedderburn

Z

Zoe Wanstall

F

Fatjon Dekaj

A

Aline Kimonyo

E

Eileen Hahn

G

Genevieve Gottschalk

F

Freya Luling Feilding

A

Alyssia McNeece

F

Fatema Merali

E

Elizabeth Ralph

E

Emily Robinson

E

Emma Sumner

A

Andrew Dick

M

Michael W. Beresford

E

Emil Carlsson

J

Joanna Fairlie

J

Jenna F. Gritzfeld

O

Oliver McClurg

K

Karen Rafferty

A

Athimalaipet V. Ramanan

T

Teresa Duerr

M

Michael Barnes

S

Sandra Ng

K

Kimme Hyrich

S

Stephen Eyre

S

Soumya Raychaudhuri

W

Wendy Thomson

J

John Bowes

J

Jeronee Jennycloss

S

Saskia Lawson-Tovey

P

Paul Martin

A

Andrew Morris

S

Stephanie Shoop-Worrall

S

Samantha Smith

M

Michael Stadler

D

Damian Tarasek

M

Melissa Tordoff

A

Annie Yarwood

W

Wei-Yu Lin

Department of Medicinal and Applied Chemistry

P

Prof Nophar Geifman

S

Sarah Clarke

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

Abstract

Article Details

Journal Info

Authors (53)

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