Background B cells (BC) play a critical role in systemic lupus erythematosus (SLE). BC depletion therapy still remains an attractive option, despite the disappointing results of randomized controlled trials. However, the effects of rituximab treatment on T –cells including regulatory T cells (Treg) in SLE have not been fully determined.
Objectives We prospectively investigated the differentiation and phenotypic changes of peripheral B cells and T regulatory lymphocytes (Treg) in patients with SLE after an intensified B-Cell depletion therapy with Rituximab
Methods Ten patients with sever SLE [2males, mean age 41.6 yrs (25–57)] with severe multiorgan involvement have been prospectively treated with IBCDT protocol due to their resistance or intolerance to previous therapy. Protocol: Rituximab (RTX) 375 mg/sm on days 1, 8, 15, 22, and 2 more doses after 1 and 2 months, associated with 2 IV administrations of 10 mg/kg of cyclophosphamide and 3 methylprednisolone pulses (15 mg/kg) followed by oral prednisone (0.8 mg/kg/day, rapidly tapered to 5mg/day by the end of the 3rd month after RTX). No further immunosuppressive maintenance therapy has been given. Circulating B cells and Treg in the peripheral blood were investigated by flow-cytometry at baseline, month 1, month 2, and every other month thereafter up to 1 year. Whole blood samples obtained in the morning, in EDTA, were stained with monoclonal antibodies against CD45, CD3, CD4 CD19, CD20, CD25 and FOXP3. Response was evaluated by assessing the changes in clinical signs and symptoms, laboratory parameters and SLEDAI score.
Results All patients had complete peripheral blood-B cell depletion after IBCDT and the CD20+ B cells were not detectable in the circulation by the 12th month (detection limit of 0.005x109/l). Upon detection of B cell depletion, we observed in 12 months a 4-fold increase in the circulating Treg (CD4+CD25+FOXP3+) (2% at baseline, 3% after 1 month, 4,5% at 6 month, 8% at 12 months). All patients achieved clinical remission after IBCTD and no flare were observed during the one-year follow-up. IBCDT resulted in a decrease of median global SLEDAI from 14.6 [11–23] to 4 [1–5] at 12 months (p<0.01)
Conclusions Our results suggest a phenotypic change of peripheral T lymphocytes as a result of B cells depletion obtained with IBCTD. Treg considered being essential in the maintenance of peripheral self-tolerance, progressively increased after B cell depletion. Such immunological re-assessment was observed in association with clinical remission in the absence of further disease flare.
Disclosure of Interest None declared
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