Pollastro S, Klarenbeek PL, Doorenspleet ME, et al. - Researchers intended to get more insight into the dynamics of lymphocyte depletion and develop new predictors of clinical response to rituximab in RA. To investigate the B cell receptor (BCR) repertoire in peripheral blood and synovial tissue samples collected from 24 seropositive patients with RA treated with rituximab, RNA-based next-generation sequencing was utilized. Following 4 weeks of rituximab-induced B cell depletion, the peripheral blood BCR repertoire of treated patients comprised of fewer, more dominant and more mutated BCR clones. No notable variances in the synovial tissue BCR repertoire were discovered until week 16 posttreatment when a decreased clonal overlap with baseline and an elevated mutation load were seen. In patients who were non-responders at month 3 (n = 5) using the European League Against Rheumatism response criteria, peripheral blood samples collected at week 4 following rituximab treatment exhibited more dominant clones in comparison with moderate responders (n = 9) and more clonal overlap with the baseline. Therefore, important alterations in BCR clonality were recognized in peripheral blood of patients 4 weeks following rituximab treatment, while variations in synovial tissue were perceived at later time points. Moreover, in the first month of treatment, incomplete depletion of the dominant baseline peripheral blood BCR repertoire may prognosticate clinical non-response at 3 months.