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FRI0006 Association Between the Increased Frequencies of Peripheral Blood Double-Negative (IGD-CD27-) B-Cell Subset and Disease Activity in Systemic Lupus Erythematosus
  1. E. Suponitskaya,
  2. A. Aleksankin,
  3. A. Mesnyankina,
  4. T. Panafidina,
  5. E. Aleksandrova,
  6. S. Solovyev,
  7. E. Nasonov
  1. Nasonova Research Institute of Rheumatology, Moscow, Russian Federation

Abstract

Background Alterations of B-cell subset distribution have been described in the peripheral blood of systemic lupus erythematosus (SLE) patients (pts), but data are still controversial and association between B-cell subsets and SLE activity remains unclear.

Objectives To examine B-cell subsets in peripheral blood of healthy donors and active SLE pts by flow cytometry before Rituximab (RTX) treatment, and to analyze the association between B-cell subsets and SLE activity.

Methods 23 active SLE pts (21F/2M); median age 36 years (range) (30-40); disease duration 6.7 years (2-8); SLEDAI-2K score 13.5 (8-19), SLEDAI-2K≥8 in 18 pts, SLEDAI-2K<8 in 5 pts; global BILAG index (calculated by i-BLIPS softwear) 20.5 (14.5-24) were assessed before RTX treatment for B-cell subsets and laboratory data: ESR, CRP, C3, C4, ANA, anti-dsDNA Ab. All pts were treated with prednisolone 17.5 (10-25) mg/day, mycophenolate mofetil (7pts), azathioprine (5pts), antimalarials (19pts), methotrexate (1pts). CD19+B cells, memory B cells (CD19+CD27-), non-switched memory B cells (CD19+IgD+CD27+), switched memory B cells (CD19+IgD-CD27+), naïve (CD19+IgD+CD27-), double-negative (CD19+IgD-CD27-), transitional (CD19+IgD+CD10+CD38++CD27-) B cells, and plasmablasts (CD19+CD38+++IgD-CD27+CD20-) were analyzed using multicolor flow cytometry.

Results The median percentages (range) of memory B cells (CD19+CD27+), non-switched memory B cells (CD19+IgD+CD27+), naïve (CD19+IgD+CD27-), and transitional (CD19+IgD+CD10+CD38++CD27-) B cells were lower in SLE pts compared to healthy donors (N=27): 1.3% (1.0-2.2) vs 2.2% (1.6-3.3), 2.1% (1.6-5.9) vs 10.0% (6.4-12.7), 58.2% (40.2-66.9) vs 65.8% (55.1-73.4), and 0.1% (0-0.1) vs 0.1% (0.1-0.3), respectively, p<0.05 for all cases. The percentages of double-negative B cells (CD19+IgD-CD27-) in SLE pts were higher than in healthy donors: 29.6% (20.9-41.3) and 9.8% (8.4-12), respectively, p<0.0001. In total SLE cohort, we found a negative association of the frequencies (r=-0.59) and absolute numbers (r=-0.59) of memory B cells (CD19+CD27+) with anti-dsDNA Ab levels, p<0.05 for both cases. The frequencies of double-negative B cells (CD19+IgD-CD27-) correlated positively with SLEDAI-2K (r=0.55), BILAG (r=0.55), ESR (r=0.60), and daily prednisolon dosage (r=0.50), p<0.05 for all cases. In active SLE pts (N=18, SLEDAI-2K≥8) this correlation was even higher: for SLEDAI-2K: r=0.67, BILAG: r=0.75, ESR: r=0.79. A strong negative association of the frequencies of double-negative B cells (CD19+IgD-CD27-) with C3 and C4 levels was observed in 17 pts with high anti-dsDNA Ab titers (>50 IU/ml): r=-0.80 and r=-0.59, respectively, p<0.05 for both cases.

Conclusions Immunophenotyping showed the decreased frequencies of memory, non-switched, naïve, transitional B-cell and increased frequencies of double-negative B cells in our active SLE cohort. Positive correlation between the level of double-negative B cells and disease activity indexes (SLEDAI-2K, BILAG), ESR, as well as a strong negative association with C3 and C4 could suggest that IgD-CD27- B cells play a prominent role in SLE pathogenesis.

Acknowledgements The authors thank Prof. H.-P. Tony, A. Koss-Kinzinger, and Z. Mahmood (University of Wuerzburg, Germany) for the assistance in the analysis of preliminary results.

Disclosure of Interest None declared

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