Decreases in the Numbers of Peripheral Blood Regulatory T Cells, and Increases in the Levels of Memory and Activated B Cells, in Patients with Active Eosinophilic Granulomatosis and Polyangiitis

Abstract

Eosinophilic granulomatosis with polyangiitis (EGPA), a rare disease characterized by the presence of allergic granulomatosis and necrotizing vasculitis, is often effectively treated with corticosteroids. However, relapse rates are high and, for unknown reasons, some EGPA patients suffer frequent relapses after entry into initial remission. Regulatory T (Treg) cells and B cells are implicated in the development and progression of EGPA. Here, we explored the influence of Treg cells and a co-stimulatory factor present on B cells on the development and course of EGPA. We studied 45 EGPA patients (19 of whom experienced frequent relapses and 26 of whom seldom relapsed) and 67 (control) patients with general asthma. We determined the counts or percentages of whole-blood cells exhibiting the following characteristics: FOXP3(+) cells among CD4(+) Treg cells; CTLA-4(+) cells among CD4(+)/CD25(+) Treg cells; and CD27(+), CD80(+), CD86(+), or CD95(+) cells among CD19(+) B cells. We also measured serum IgG concentrations. Compared with patients with asthma or seldom-relapsing EGPA, frequently relapsing EGPA patients with active disease exhibited decreased counts of Treg cells and increased percentages of B cells that scored as CD80(+), CD27(+), or CD95(+). Patients with frequently relapsing EGPA had increased percentages of CD27(+) and CD95(+) B cells, and fewer CD19(+) B cells, than did patients in the other two groups. Lower CD19(+) B cell counts were associated with reduced Treg cell counts and a lower serum IgG concentration. In patients with frequently relapsing EGPA, decreases in Treg cell numbers and increased percentages of activated B cells may induce apoptosis of B cells.