OBJECTIVE: To elucidate the diversity of systemic lupus erythematosus (SLE) 
based on immunophenotyping.
METHODS: Peripheral blood mononuclear cells were obtained from 143 SLE patients 
and 49 healthy individuals. Circulating B, T, and dendritic cells were defined 
using flow cytometric analysis as recommended by the Human Immunology Project 
Consortium. Based on these results, immunophenotypes were distinguished by 
principal components analysis (PCA), and cluster analysis was used to classify 
SLE patients into subgroups.
RESULTS: The proportions of Treg and follicular helper T (Tfh) cells were higher 
in SLE patients than in healthy controls, whereas Th1 and Th17 cell proportions 
did not differ. Proportions of class-switched memory B cells and IgD-CD27- B 
cells were increased in SLE patients as well. The largest difference compared to 
the control group was observed in the proportion of plasmablasts, which was 
higher in SLE patients and correlated with disease activity as assessed with the 
British Isles Lupus Assessment Group index. PCA indicated that the 
immunophenotype of SLE patients consisted of abnormalities of the T and B cell 
axes. Cluster analysis showed that the SLE patients could be stratified into 3 
subgroups (with high proportions of plasmablasts in all groups): patients who 
did not show the characteristic features (T cell-independent group), patients 
with a high percentage of Tfh cells (Tfh-dominant group), and patients with a 
high percentage of memory Treg cells (Treg-dominant group). The percentage of 
patients whose SLE was resistant to treatment was highest among the Tfh-dominant 
group.
CONCLUSION: Our study indicates that patients with active SLE can be divided 
into 3 subgroups based on T cell heterogeneity. Further immunophenotyping 
studies should help elucidate the pathogenesis of SLE and provide important 
information for the development of new therapies.