Pollastro S, et al. - Via an RNA-based next-generation sequencing used to analyze the B cell receptor (BCR) repertoire in peripheral blood and synovial tissue samples collected from 24 seropositive patients with rheumatoid arthritis (RA) who were treated with rituximab, the researchers intended to gain more insight into the dynamics of lymphocyte depletion and generate new predictors of clinical response to rituximab in RA. The peripheral blood BCR repertoire of treated patients contained fewer, more dominant and more mutated BCR clones post-four weeks of rituximab-induced B cell depletion. No significant alterations in the synovial tissue BCR repertoire could be identified until week 16 post-treatment when a diminished clonal overlap with baseline and an elevated mutation load were observed. Hence, in peripheral blood of patients 4 weeks after rituximab treatment, significant changes in BCR clonality were noticed, while alterations in synovial tissue were recognized at later time points. Further, clinical non-response at 3 months could be forecasted through incomplete depletion of the dominant baseline peripheral blood BCR repertoire in the first month of treatment.