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104 A mass cytometry (CYTOF) approach to study B cell alterations during baff blockade treatment with belimumab in systemic lupus erythematosus
  1. I Parodis1,
  2. D Ramsköld1,
  3. L Tadepally2,
  4. Y Chen2,
  5. A Zickert1,
  6. J Mikes2,
  7. K Amara1,
  8. A Achour2,
  9. P Brodin2,
  10. I Gunnarsson1 and
  11. V Malmström1
  1. 1Karolinska Institutet, Department of Medicine- Rheumatology Unit, Stockholm, Sweden
  2. 2Karolinska Institutet, Department of Medicine Solna- Science for Life Laboratory, Stockholm, Sweden

Abstract

Background and aims Belimumab is a monoclonal antibody that inhibits soluble B lymphocyte stimulator (BLyS, also known as BAFF), approved for the treatment of systemic lupus erythematosus (SLE). Here, we sought to identify B cell alterations during belimumab treatment.

Methods Twenty-three SLE patients treated with belimumab were enrolled. Peripheral blood mononuclear cells were collected and cryopreserved at treatment initiation and at regular follow-up visits for up to 3 years. The samples were simultaneously assayed using mass cytometry. Cell counts were adjusted for total lymphocyte counts.

Results CD20+ B cells decreased over time (p<0.0001). We observed a rapid reduction of naïve (CD19+CD20+IgD+IgM+CD27-) and age-associated B cells (CD19+CD20+CD11c+CD21-) already at the first follow-up visit (month 3), followed by a continuous decrease (p<0.0001 for both subsets), while double-negative memory B cells (CD19+CD20+IgD-CD27-) declined significantly first at month 6 (p=0.033) and pre-switching B cells (CD19+CD20+IgD+CD27+) showed a trend towards a decrease (p=0.052). Plasma cells (CD138+CD38+CD27+CD19+CD3e-CD20-) and switched memory B cells (CD19+CD20+CD27+IgD-) remained stable during the study period, as did T cells and monocytes (p>0.2). Despite continuously decreasing SLE Disease Activity Index, immunological changes correlated with clinical improvements only during early time points (month 0–3). Interestingly, high baseline B cell counts were predictive of non-attaining Lupus Low Disease Activity State at month 24 (area under the ROC-curve: 0.95).

Conclusions B cell alterations betided in two distinct phases, a rapid early and a gradual late phase. Late clinical improvements might reflect preceding immunological changes, implying that early treatment evaluation and discontinuation might underestimate delayed improvements reflecting the late B cell changes.

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