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

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.