Strategic treatment in which different bDMARDs were selected according to phenotypic differences in helper T cells showed significantly higher efficacy than standard bDMARD therapy, indicating the value of precision medicine.

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.

The association found between Tfh cells and plasmablasts, linked with biological plausibility, suggests that Tfh cells contribute to the pathogenesis of IgG4-RD. Our results also suggested that controlling the Tfh cell-plasmablast axis could be a novel therapeutic strategy for treating IgG4-RD.

Molecular targeted therapies induced different changes in different immune cell phenotypes. Among the phenotypes, Tfh cells seem a potential target for abatacept. Immunophenotypic analysis might be useful for prediction of the response to bDMARDs.

Our findings suggest that IL-12-mediated co-activation of STAT1 and STAT4 alters histone modification, resulting in differentiation of Tfh-Th1-like cells that are characteristically expanded in patients with SLE. This could be one of the underlying mechanisms responsible for expansion of Tfh-Th1-like cells and potentially helpful towards development of cell-specific treatment for SLE.