To investigate the efficacy and safety of blood purification followed by sequential rituximab and belimumab treatment in systemic lupus erythematosus patients.Meanwhile, analyze the impact of blood purification treatment and B-cell targeted therapy on peripheral blood B-cell subsets in SLE patients.

Eight patients with moderate to severe disease activity accepted plasmapheresis and immunoadsorption, followed by sequential rituximab and belimumab as combination treatment group in our study. Furthermore, nine patients treated by sequential rituximab and belimumab were included as control group. We evaluated the efficacy according to the changes of anti-dsDNA level, complement level, proteinuria level and systemic lupus erythematosus disease activity index (SLEDAI) 2k score. In addition, we observed the creatinine, transaminase and blood cell count to assess the safety. Flow cytometry were used to measure changes in the CD19+ B cell, naïve(CD45dim+CD3-CD14-CD27-CD19+), memory(CD45dim+CD3-CD14-CD27+CD19+), and plasmablast (CD45dim+CD3-CD14-CD27+CD38briCD19dim+/-) cell over the course of treatment. 

Compared to sequential rituximab and belimumab group, combination treatment group removed anti-dsDNA rapidly(P=0.03), showed remarkable reduction of proteinuria(P=0.04) and SLEDAI(P=0.03). Moreover, combination treatment group reduced the number of plasmablast cells significantly(P=0.04). Peripheral memory B cells gradually decreased in patients treated with belimumab and rituximab, while patients treated with  combination treatment experienced an immediate and marked reduction in peripheral memory B cells.There were no significant differences in complement and naive B cells between the two treatment groups.Also,no significant change of creatinine, blood urea nitrogen, white blood cell, red blood cell and hemoglobin before and after treatment.

For systemic lupus erythematosus, blood purification followed by sequential rituximab and belimumab treatment can reduce the anti-dsDNA level, proteinuria, SLEDAI score and plasmablast cells significantly, prominently and safely. In our study, we justified that blood purification combined B-cell targeted therapy was efficient and safe for moderately-to-severely systemic lupus erythematosus patients. Blood purification as a additional therapy can be used in SLE patients with high level of anti-dsDNA to promote rapid disease relief.