Arthritis Rheumatol. 2025 Mar 17. doi: 10.1002/art.43157. Online ahead of print.
ABSTRACT
OBJECTIVE: Disordered T peripheral helper (Tph)-B cell interactions have been implicated in several forms of inflammatory arthritis, including oligoarticular juvenile idiopathic arthritis (oligo 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 vs. blood of patients and controls. Compared to male patients, females with oligo JIA had greater proportions of intra-articular Tph cells that expressed B cell help factors as well as Bmem, plasmablasts, and age/autoimmune-associated B cells. The sex differences in B cells were observed only in the joints and not found in the blood or tonsil nor were they explained by other disease features such as age of onset, ANA status, or severity. Bmem cells in female SF displayed characteristics of autoreactivity, including longer CDR3 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 females with oligo JIA compared to blood of JIA patients and controls.
CONCLUSIONS: 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.
PMID:40098343 | DOI:10.1002/art.43157