B Cell Reconstitution and T Helper Cell Balance After Rituximab Treatment of Active Primary Sjogren's Syndrome A Double- Blind, Placebo-Controlled Study

Objective. To assess the phenotype of reconstituting B cells after B cell depletion, and to assess the effect of reconstitution on the balance of Treg cells and effector T cells in patients with active primary Sjogren's syndrome (SS). Methods. Twenty-eight patients with primary SS were treated on days 1 and 15 with either rituximab (n = 19) or placebo (n = 9). The frequencies and absolute numbers of circulating B cell subsets, Treg cells, and effector T cells were examined in fresh blood samples by 4-color flow cytometry at baseline and 5, 12, 24, 36, and 48 weeks after the first infusion. The results in rituximab-treated patients were compared with those in patients receiving placebo and with those in age-and sex-matched healthy controls (n = 10). Results. At baseline, patients with primary SS displayed several abnormalities in B cell homeostasis, including a significant reduction of CD27+ B cells and expansion of CD27- B cells, compared with healthy controls. At week 48 after rituximab treatment, the majority of emerging B cells exhibited a phenotype of transitional B cells. Although recovery of CD27+ memory B cells was delayed after rituximab treatment, a significant increase in Ig class-switched memory B cells within the memory pool was observed. In addition, percentages and absolute numbers of Treg cells and effector T cells, as well as ratios of effector T cells to Treg cells, did not change significantly after rituximab treatment. Conclusion. The characteristics of reconstituted B cells in patients with primary SS following depletion by rituximab treatment showed dominance of transitional B cells during the early recovery phase, which corresponds to bone marrow-derived repopulation. The depletion of B cells did not influence the balance of peripheral Treg cells and effector T cells.