SAT0179 The blood b-cell subsets and effect of tocilizumab therapy on them in patients with rheumatoid arthritis. (12th June 2018)

• Record Type: Journal Article
• Authors: Gerasimova, E.; Popkova, T.; Aleksankin, A.; Davidyan, S.; Martinova, A.; Aleksandrova, E.
• Is Part Of: Annals of the rheumatic diseases. Volume 77(2018)Supplement 2
• Page Start: 950
• Page End: 951
• Publication Date: 2018-06-12
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-eular.4566
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : 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