Peripheral Immunophenotyping Identifies Three Subgroups Based on T Cell Heterogeneity in Lupus Patients.

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. [ABSTRACT FROM AUTHOR]