Eosinophilic granulomatosis with polyangiitis exhibits T cell activation and IgG4 immune response in the tissue; comparison with IgG4-related disease

Abstract

Objective To study the pathophysiological differences of EGPA and IgG 4 -related disease (RD) by clarifying their clinical, pathological and immunological features. Methods Clinical and pathological findings were compared in patients with EGPA and IgG 4 -RD. Peripheral blood mononuclear cells were used for comprehensive flow cytometric analysis. Results An elevation of the IgG4 level was found in all EGPA cases, with the accompanying pathological findings of lymphocytic infiltration and fibrosis observed in 30.8% patients, and the elevation of IgG 4 /IgG ratio in 61.5% patients. However, actual IgG 4 levels, as well as the degree of the infiltration of IgG 4 -positive plasma cells, were still higher in patients with IgG 4 -RD than patients with EGPA. Examination by ACR/EULAR classification criteria showed only 13.6% of the EGPA patients met entry criteria, while all of them met the exclusion criteria. In regard to the immunophenotyping, EGPA patients had increases in activated CD4 and CD8 T cells compared with the healthy controls. However, no such similar changes occurred in IgG 4 -RD patients. On the other hand, both the EGPA and IgG 4 -RD patient groups had correlated increased plasmablasts and Tfh. These results indicate the presence of two axes: namely, the activation of T cells and that of B cells. Both axes are present in EGPA, but the T cell activation axis was not observed in IgG 4 -RD. Conclusions The elevation of serum IgG 4 as well as pathological IgG 4 infiltration are not specific. Meanwhile, EGPA and IgG4-RD differ in immunological phenotypes, indicating the possible importance of the predominant activation of T cells in the development of vasculitis.