Background/Purpose:

Numerous reports suggest that B cell depletion therapy (BCDT) using rituximab is effective in patients with systemic lupus erythematosus (SLE). However, two major trials did not confirm these results. We, and others, have shown that the characteristics and kinetics of repopulating B cells are associated with different clinical responses to BCDT. B cell activating factor / B Lymphocyte Stimulator (BAFF / BLyS) is a key mediator of B cell survival and self-tolerance, which is over-expressed in many patients with SLE. The present study examines changes in serum BAFF at disease flares and remission following BCDT and repopulation of peripheral B cells, and assesses the relationship between serum BAFF, B cell number and autoantibody levels according to treatment outcome.

Methods:

35 patients with SLE, treated with one or more cycles of BCDT using rituximab, cyclophosphamide and methylprednisilone, had stored serum samples available for analysis. Patients were followed up until disease flare, further BCDT or for a minimum of 18 months following BCDT. Anti-dsDNA levels, immunoglobulins and CD19+ counts were recorded during follow up. Clinical disease was assessed using the BILAG index. Serum BAFF was measured during disease flare prior to BCDT and at subsequent relapse or remission, using a human BAFF ELISA.

Results:

Following initial BCDT, 10 patients remained in remission for the duration of follow up. Twenty-five patients went on to relapse, of which 22 were treated with further BCDT. BAFF levels were positively correlated with B cell numbers (R = 0.65, p < 0.05) and serum IgG (R = 0.56, p < 0.01) prior to BCDT, but did not predict subsequent treatment outcome or time to repopulation following rituximab (p > 0.05). However, serum BAFF after BCDT and subsequent B cell repopulation was significantly higher at disease relapse compared to levels in patients who remained in remission (p < 0.01) but also compared with the disease flare prior to BCDT (p < 0.05). Following BCDT serum BAFF was inversely correlated with B cell numbers at disease flare (R =  -0.44, p < 0.05), with flare at lower B cell numbers associated with the highest BAFF levels. Changes in serum BAFF during relapse or remission strongly correlated with change in anti-dsDNA antibody levels (R = 0.62, p < 0.001).

Conclusion:

The present data suggest a significant role for BAFF in driving disease flare after B-cell repopulation following BCDT. In some patients sequential BCDT promoted ever increasing BAFF levels accompanied by rising anti-DNA antibodies and flare even at low B-cell numbers. Therefore, our data justifies the judicious use of BAFF blockade in a subgroup of lupus patients after BCDT.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/elevated-serum-b-cell-activating-factor-baffblys-characterises-disease-relapse-following-rituximab-in-systemic-lupus-erythematosus/