Pemphigus vulgaris (PV) is an autoimmune blistering disease caused by auto-antibodies (auto-ab) against desmoglein (Dsg) 3 and Dsg1. Auto-ab production depends on a close interaction between T and B cells. Rituximab (Rtx), a monoclonal ab that selectively binds CD20 with long-lasting depletion of B cells, has been suggested to also affect the T cell compartment by impeding the cross-talk between T and B cells. Nonetheless, the effect of Rtx on distinct T cell subsets like T follicular helper (Tfh) cells remains to be elucidated. In this study, we investigated alterations of different T cell subsets in patients with PV (n=9) and PF (n=3) treated with Rtx in comparison to healthy controls (HC, n=20) and followed multiple T and B cell populations for up to 12 months. Pemphigus patients were characterized by significantly higher levels of circulating CXCR5-CCR6-CXCR3- Th2 cells while, CXCR5-CCR6+CXCR3- Th17.1 cells, a recently described Th cell subset were reduced. Likewise, CXCR5+CCR6-CXCR3- Tfh1 cells showed decreased frequencies, whereas CXCR5+CCR6-CXCR3+ Tfh17 cells were increased. Follow-up analysis after Rtx treatment revealed a ‘normalization’ of the Th and Tfh subset distribution in pemphigus patients except for Tfh17.1 cells. Additionally, we found that CD27highCD38highCD138++ plasma cells re-emerged in peripheral blood prior to total CD19+ or CD19+CD27+ memory B cells after Rtx treatment and correlated with the individual ratio of Tfr to Tfh cells. This finding became even more evident after analysis of three patients suffering from a relapse and accompanied by increased Tfh/Th cell ratios. In conclusion, our results indicate that the Tfr/Tfh ratio might serve as an indicator of reconstituted humoral activity at the T cellular level.

Modulation of the T helper and T follicular helper cell distribution in pemphigus patients by B cell-depleting therapy