Background Targeting B cell activating factor (BAFF) by belimumab is effective in systemic lupus erythematosus (SLE) (1), and leads to a partial B cell depletion (2,3). However, which subset of B cells may be the main therapeutic target of belimumab in SLE, either why the response under belimumab is usually delayed in time is still unclear.

Objectives Our purpose was to study the effect of belimumab on different B cell subsets in SLE and in particular the expression of BAFF receptor (BAFFR) on B cells through 12 months of belimumab treatment.

Methods Seven patients with SLE (all female, age 46,7±7,8 years, mean disease duration of 13,8±4,2 years) undergoing belimumab therapy from May 2013 were studied. All patients received at least two immunosuppressors before belimumab; all patients were taking glucocorticoids at baseline (10±12 mg/day), and 6/7 were also taking at least one immunosuppressor. Mean SELENA-SLEDAI score at baseline was 9,7±2,7. Samples were collected and analyzed at baseline (T0), month +3 (T3), month +6 (T6), month +9 (T9) and month +12 (T12, 5 pts) for clinical and biological parameters. B cells subsets were characterized by multiparametric flowcytometry on a BD FACSCanto flowcytometer. The expression of BAFFR was also analyzed as Mean Fluorescence Intensity (MFI). Data were reported as mean ± standard error.

Results In the group of 7 SLE patients studied, a decrease of the SELENA-SLEDAI score from 9,7±2,7 at T0, to 6,1±1,9 at T3, to 5,0±1,0 at T6, to 4,4±0,8 at T9 and finally to 4,1±0,9 at T12 was documented. At T0 peripheral blood counts of CD19+ cells were low (median 46 cell/μl, range 1,1-267), possibly because of the past and concomitant immunosuppressive treatments and the chronic glucocorticoids administration. CD19+CD27- cells decreased after belimumab treatment from 60±56 cell/μl at T0 to 24±14 cell/μl at T3, and then remained low over time (21±11 cell/μl at T6, 25±19 cell/μl at T9 and 23±14 cell/μl at T12). By contrast, CD19+CD27+ cells showed a transient increase as absolute counts at T6 (from 17±13 cell/μl at T0 to 23±17 cell/μl at T6), while they markedly decreased from T6 to T12 (9±7 cell/μl). BAFFR expression remained unchanged over time during therapy as percentage of B cells (mean 97±1,7% at T0 vs. 97±2% at T9); however, a transient increase in BAFFR MFI was observed from T0 to T3 (11,6±1,9 to17±4,7), and then decreased to T12 (10,9±1,5). The count of CD27+ B cells and the mean MFI BAFFR expression showed a similar curve over time, differently from CD19+CD27- B cells (figure 1).

• Download figure
• Open in new tab
• Download powerpoint

Conclusions Hyperexpression of BAFF receptor on CD27+B cells occurs shortly after belimumab consistently with the increase in the CD27+ B cell count in the first three months of treatment. Subsequently, the BAFFR expression decrease is followed by the lowering of CD27+ B cells from T6 to T12. The intensity of BAFFR expression on CD27+ B cells may explain the pharmacodynamic of belimumab in SLE. Since belimumab acts slowly in SLE, the results observed support the hypothesis of a therapeutic effect of belimumab also on CD27+ B cells.

References

1. Furie R et al. Arthritis Rheum 2011.

2. Stohl W et al. Arthritis Rheum 2012.

3. Jacobi AM et al. Arthritis Rheum 2010.

Disclosure of Interest None declared