B-CELL RECONSTITUTION AND T-CELL BALANCE AFTER RITUXIMAB TREATMENT OF ACTIVE PRIMARY SJÖGREN'S SYNDROME

W.H. Abdulahad, J.M. Meijer, A. Vissink, C.G.M. Kallenberg, H. BootsmaDepartments of Rheumatology and Clinical Immunology Departments of Oral and Maxillofacial Surgery, University Medical Center Groningen, Groningen, NetherlandsObjectives: To analyze the phenotype and the state of activation of reconstituting B-cells after B-cell depletion, and to assess the effect of reconstitution on regulatory (TReg) and effector (Teff) T-cell numbers in patients with active primary Sjögren's syndrome (pSS). Methods: Twenty-nine patients with pSS were treated on days 1 and 15 with either rituximab (RX, n=20) or placebo (PL, n=9). B-cell numbers and phenotypes were examined in fresh blood samples by four-color cytometry at baseline and at 5, 12, 24, 36, and 48 weeks after infusions. The distribution of immature naïve (CD38HighCD27-CD19+), mature naïve (CD38LowCD27-CD19+), pre-switched memory (IgD+IgM+CD27+CD19+), post-switched memory (IgD-IgM-CD27+CD19+) B-cells, and plasma cells (CD38HighCD27HighCD19+) was examined. In addition, numbers of both TReg cells (CD3+CD4+CD25HighCD127-) and Teff cells (CD3+CD4+CD25+CD127+) were also analyzed at all timepoints. Results: At baseline, patients with pSS displayed several abnormalities in B-cell homeostasis, including a significant reduction of pre-switched memory B-cells and expansion of immature- and mature naïve B-cells, compared with healthy controls (n=10). Following RX-treatment (at week 48), a majority of emerging B-cells revealed a phenotype of immature naïve cells. Although the recovery of memory B-cells was delayed, a significant increase in post-switched and a significant decrease in pre-switched memory B-cells was observed post-RX when compared with pre-RX and post-PL. Remarkably, no significant differences in the percentages of plasma cells were found at 48 weeks compared to pre-RX-treatment. Furthermore, percentages and absolute counts of TReg and Teff cells, as well as TReg:Teff ratios, showed no significant changes after RX compared to baseline. Conclusion: B-cell reconstitution after RX-treatment starts with immature naïve cells followed by post-switched memory cells that probably include autoreactive B-cells. RX-treatment did not influence peripheral TReg and Teff cells. Disclosure of Interest: None declaredCitation: Annals of the Rheumatic Diseases, volume 68, supplement 3, year 2009, page 254Session: SLE, Sjgren's and APS Treatment (Poster Presentations )