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Disease activity in systemic lupus erythematosus (SLE) is usually assessed with complex disease activity scores comprising a variety of different parameters. In order to determine whether SLE disease activity correlates with abnormal B lymphocyte activity, B cell subsets were analyzed, and their relationship to clinical and humoral measures of disease activity was assessed. The distribution of B cell subsets was determined by fluorescence-activated cell sorting analysis and assessed in relation to the autoantibody profile, disease activity measured by the SLE Disease Activity Index (SLEDAI) and the European Consensus Lupus Activity Measure scores, disease duration, and therapy. The number and frequency of CD27high plasma cells were significantly correlated with the SLE disease activity indices and with the titer of anti–double-stranded DNA (anti-dsDNA) autoantibodies. Circulating B cell subsets were not influenced by age or sex, but appeared to relate to the duration of disease and the therapeutic regimen, with the number and frequency of CD27high plasma cells increasing and those of CD27- naive B cells decreasing over time. Patients were divided into those with a SLEDAI score of 0–8 (low disease activity) and those with SLEDAI score >8 (high disease activity). Patients with high disease activity had an increased frequency of both CD19+ B cells and CD27high plasma cells. By using a nonparametric data sieving algorithm, we observed that these B cell abnormalities provided predictive values for nonactive and active disease of 78.0% and 78.9%, respectively. The predictive value of the B cell abnormalities (78.9%) was greater than that of the humoral/clinical data pattern (71.4%), including anti-dsDNA antibody levels, circulating immune complexes, increased erythrocyte sedimentation rate, mucocutaneous involvement, and acute renal involvement. Flow cytometric monitoring of B cell subsets in the peripheral blood provides new insights into abnormalities of B cell function in SLE and may also be a diagnostically valuable option for monitoring the activity of this autoimmune disease. [ABSTRACT FROM AUTHOR]