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SAT0179 The blood b-cell subsets and effect of tocilizumab therapy on them in patients with rheumatoid arthritis
  1. E. Gerasimova1,
  2. T. Popkova2,
  3. A. Aleksankin2,
  4. S. Davidyan3,
  5. A. Martinova2,
  6. E. Aleksandrova2
  1. 134A, Kashirskoe Shosse, Gerasimova Elena
  2. 234A, Kashirskoe Shosse
  3. 3V.A.Nasonova Research Institute of Rheumatology, Moscow, Russian Federation


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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