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

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 CD21^lo 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.