Background: The use of the IL-6 receptor antagonist, tocilizumab (TCZ), in rheumatoid arthritis (RA) produce pleiotropic effects that also involve circulating B-cells. Preliminary reports have suggested that B cell function and humoral immune responses might be modulated by TCZ treatments in RA pts.
Objectives: To assess the effect of 12 months (mo) TCZ therapy on B-cell phenotype and gene expression in RA and to analyze the association between B-cell subsets and RA activity.
Methods: 24 active RA pts (20 F/4 M); median age 55[49; 64] years; disease duration 72[24; 108]m; DAS28 score 5,8[5,3;6,3]; RF+100%, ACCP+ 87% were treated in an open-label study with tocilizumab (8 mg/kg every 4 weeks). Immunophenotyping was performed at baseline and 12 mo. Pts were assessed for B-cell subpopulations and laboratory data: ESR, RF, ACCP, CRP. CD19+B cells, memory B cells (CD19+CD27+), non-switched memory B cells (CD19+CD27+ IgD+), switched memory B cells (CD19+ CD27+IgD-), naive (CD19+CD27-IgD+), double-negative (CD19+CD27-IgD-), transitional (CD19+CD38++CD10+IgD+CD27-) B cells, and plasmablasts (CD19+CD38+++CD27+IgD-CD20-) were analyzed using multicolor flow cytometry.
Results: At baseline, the absolute counts of memory B cells (CD19+CD27+) and switched memory B cells (CD19+CD27+IgD-) were lower in RA pts compared to healthy donors: 0,0015(0,001–0,003) vs 0,003(0,001–0,007) and 0,01(0,005–0,02) vs 0,02(0,01–0,04), respectively, p<0,01 for both cases. At baseline, a significant correlation was found in RA pts between absolute counts of memory B cells (CD19+CD27+) and CRP (r=0,50, p<0,05); the percentage and absolute counts of plasmablasts (CD19+CD38+++CD27+IgD-CD20-) and RF (r=0,41 and r=0,52, p<0,05). After 12 mo of TCZ therapy, 54% of pts were categorized as good responders, 46% of pts – as moderate responders according to the EULAR response criteria. Reductions in the percentages and absolute counts of plasmablasts (CD19+CD38+++CD27+IgD-CD20-) were documented after 12 mo of TCZ therapy: 0,15%(0,1–0,3) vs 0,1%(0,01–0,1) and 0,0003(0,00007–0,004) vs 0,0001(0–0,0003), respectively, p<0,05. The median percentages/absolute counts of switched memory B cells (CD19+CD27+IgD-) were 6,8%(3,6–11,6)/0,01(0,005–0,02) at baseline; and 3,1%(1,1–4,2)/0,003(0,002–0,006) after 12 mo of TCZ therapy, p>0,05. After 12 mo of TCZ therapy, the median percentages and absolute counts of memory B cells (CD19+CD27+) and switched memory B cells (CD19+CD27+IgD-) became lower in RA pts than in the controls: 1,0%(0,7–1,2) vs 2,2%(1,1–3,0); 0,001(0,006–0,003) vs 0,003(0,001–0,007); 3,1%(1,1–4,2) vs 12,8%(9,3–17,0); 0,003(0,002–0,006) vs 0,02(0,01–0,04), respectively, p<0,05, respectively, for all cases. Other B-cell subpopulations did not changed after 12 mo of TCZ therapy as compared to baseline values.
Conclusions: Immunophenotyping in pts with active RA showed the decrease in the absolute counts of memory B cells (CD19+CD27+), switched memory B cells (CD19+ CD27+IgD-) as compared to healthy subjects. Positive correlation between the counts of memory B cells and plasmablasts and values of laboratory indicators of RA (CRP, RF) suggests that B-lymphocytes may be involved in RA pathogenesis. The reduction in the levels of plasmonoblasts after 12 mo of TCZ therapy was observed.
Disclosure of Interest: None declared
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