Relationship between NK Cell Activation and Clinical Response in Rheumatoid Arthritis Treated with Rituximab

INTRODUCTION: We investigated the relationship between the anti CD20 therapy and the NK cell phenotype in patients with Rheumatoid Arthritis (RA). METHODS: patients with seropositive RA according to the ACR criteria that was refractory to conventional and anti TNF alpha agents were studied. All patients were treated with Rituximab (1.0 g at days 1 and 15). At baseline and day 30 were collected: absolute counts of B cells (CD19+), total T cells (CD3+), helper (CD3+CD4+), cytotoxic (CD3+CD8+) and NK (CD16+CD56+). As NK activation marker was used CD54bright expression. Disease activity was primarily assessed using the the Clinical Disease Activity Index (CDAI); in addition, we calculated the Disease Activity Score 28-joint assessment (DAS28). RESULTS: 18 patients were enrolled (mean age ± SD 58.6 ± 2.8 years old). After the rituximab course, as expected CD19+ cells were not detectable, the cytotoxic lymphocytes and CD56+CD16+ cells downregulated (283 ± 34 and 85 ± 15 respectively), instead an up regulation of CD56+CD16+CD54bright was observed (187 ± 43). The dynamic of NK cells activation was significantly associated with clinical variables (r=0.811, p<0.001). CONCLUSIONS: our data suggest a role of rituximab therapy in varying NK phenotype in patients with RA and show that NK cells activation correlates with clinical response.