Aberrant B cell activation and B cell subpopulations in rheumatoid arthritis: analysis by clinical activity, autoantibody seropositivity, and treatment

Clin Exp Immunol. 2023 Jul 19:uxad076. doi: 10.1093/cei/uxad076. Online ahead of print.


Few studies analyze the role of B cells subpopulations in rheumatoid arthritis (RA) pathophysiology. Therefore, this study aimed to analyze the differences in B cell subpopulations and B cell activation according to disease activity, RA subtype, and absence of DMARDs therapy. These subgroups were compared with control subjects (CS). 139 subjects were included, of which 114 were RA patients and 25 were controls. Patients were divided into 99 with seropositive RA, six with seronegative RA, and nine without DMARDs. The patients with seropositive RA were subclassified based on the DAS28 index. A 7-color multicolor flow cytometry panel was used to identify B-cell immunophenotypes and cell activation markers. There were no changes in total B cells frequencies between RA patients and controls. However, a lower frequency of memory B cells and pre-plasmablasts was observed in seropositive RA compared to controls (p <0.0001; p =0.0043, respectively). In contrast, a higher frequency of mature B cells was observed in RA than in controls (p =0.0002). Among patients with RA, those with moderate activity had a higher percentage of B cells (p =0.0021). The CD69 + marker was increased (p <0.0001) in RA compared to controls, while the CD40 + frequency was decreased in patients (p <0.0001). Transitional, naïve, and double-negative B cell subpopulations were higher in seronegative RA than in seropositive (p <0.01). In conclusion, seropositive and seronegative RA patients, there are alterations in B cell activation and B cell subpopulations, independently of clinical activity and DMARDs therapy.

Keywords: B-cell subpopulations; CD40; CD69; DAS-28; Rheumatoid Arthritis.