Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Aug;77(8):1092-1105.
doi: 10.1002/art.43157. Epub 2025 May 21.

Sex Differences in B Cells From the Joints of Children With Oligoarticular Juvenile Idiopathic Arthritis

Ki Pui Lam  1 , Claudia Harris  2 , Maria L Taylor  3 , Daniela Fernandez-Salinas  4 , Jing Cui  5 , Biju Issac  6 , Liang Sun  6 , Indu Raman  7 , Chengsong Zhu  7 , Maryrose Hahn  2 , Maryam Ashoor  1 , Ahmad Bakhsh  1 , Maria C Bryant  1 , Siobhan Case  8 , Mia Chandler  1 , Joyce C Chang  1 , Ezra Cohen  1 , Fatma Dedeoglu  1 , Olha Halyabar  1 , Jonathan S Hausmann  9 , Melissa Hazen  1 , Daniel Ibanez  1 , Liyoung Kim  1 , Jeffrey Lo  1 , Mindy S Lo  1 , Esra Meidan  1 , Megan Perron  1 , Helene Powers  1 , Mary Beth Son  1 , Holly Wobma  1 , Erin Janssen  10 , Pui Y Lee  1 , Peter A Nigrovic  8 , Laurie Ohlms  11 , A Eliot Shearer  11 , Margaret H Chang  1 , Maria Gutierrez-Arcelus  4 , Lauren A Henderson  1
Affiliations

Sex Differences in B Cells From the Joints of Children With Oligoarticular Juvenile Idiopathic Arthritis

Ki Pui Lam et al. Arthritis Rheumatol. 2025 Aug.

Abstract

Objective: Disordered T peripheral helper (Tph)-B cell interactions have been implicated in several forms of inflammatory arthritis, including oligoarticular (oligo) juvenile idiopathic arthritis (JIA). We sought to evaluate the Tph-B cell axis in oligo JIA through an analysis of intra-articular B cells.

Methods: B cells from the blood and synovial fluid (SF) of 44 children with oligo JIA were compared to those from the blood and tonsils of controls. Flow cytometry, B cell receptor (BCR) repertoire analysis, and autoantibody profiling were used to characterize B cells.

Results: Memory B (Bmem) cells and heterogeneous subsets of CD21lo B cells were enriched in oligo JIA-SF versus blood of patients and controls. Compared to male patients, female patients with oligo JIA had greater proportions of intra-articular Tph cells that expressed B cell help factors as well as Bmem cells, plasmablasts, and age-/autoimmune-associated B cells. The sex differences in B cells were observed only in the joints and were not found in the blood or tonsil, nor were they explained by other disease features such as age at onset, antinuclear antibody status, or severity. Bmem cells in SF from female patients displayed characteristics of autoreactivity, including longer complementarity determining region 3 lengths and increased usage of autoreactive BCR gene segments, which were not found in blood Bmem cells. A diverse array of autoantibodies accumulated in the SF of female patients with oligo JIA compared to the blood of patients with JIA and controls.

Conclusion: These findings demonstrate prominent B cell dysregulation in oligo JIA and implicate sex as an important biologic factor in B cell responses in this disease.

PubMed Disclaimer

Conflict of interest statement

M Chandler received grant support from CARRA. JCC received salary support from CARRA and consulting fees from Century Therapeutics. FD and MSL received editorial income from UpToDate. MBS received salary support from CARRA. HW is co-founder and equity holder for Regatta Bio. EJ received consulting fee from SOBI via IQVIA. PAN has received investigator-initiated research grants from BMS and Pfizer, consulting fees from Alkermes, Apollo, BMS, Exo Therapeutics, Merck, Novartis, Pfizer, Qiagen and Sobi, has equity in Edelweiss Immune Inc., and has received authorship and editorial income from UpToDate, the American Academy of Pediatrics, Arthritis & Rheumatology. LAH received salary support from CARRA. LAH has received investigator-initiated research grants from BMS and consulting fees from Sobi, Pfizer, and Adaptive Biotechnologies. None of the funding sources played a role in the design, collection, analysis, or interpretation of data presented in this manuscript.

References

    1. Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 2004;31(2):390–2. - PubMed
    1. Oen KG, Cheang M. Epidemiology of chronic arthritis in childhood. Seminars in arthritis and rheumatism. 1996;26(3):575–91. - PubMed
    1. Ravelli A, Varnier GC, Oliveira S, et al. Antinuclear antibody-positive patients should be grouped as a separate category in the classification of juvenile idiopathic arthritis. Arthritis and rheumatism. 2011;63(1):267–75. - PubMed
    1. Ravelli A, Felici E, Magni-Manzoni S, et al. Patients with antinuclear antibody-positive juvenile idiopathic arthritis constitute a homogeneous subgroup irrespective of the course of joint disease. Arthritis and rheumatism. 2005;52(3):826–32. - PubMed
    1. Saurenmann RK, Levin AV, Feldman BM, et al. Prevalence, risk factors, and outcome of uveitis in juvenile idiopathic arthritis: a long-term followup study. Arthritis and rheumatism. 2007;56(2):647–57. - PubMed

LinkOut - more resources