Objective: To study the pathophysiological differences of EGPA and IgG4-related disease (RD) by clarifying their clinical, pathological and immunological features.
Methods: Clinical and pathological findings were compared in patients with EGPA and IgG4-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 IgG4/IgG ratio in 61.5% patients. However, actual IgG4 levels, as well as the degree of the infiltration of IgG4-positive plasma cells, were still higher in patients with IgG4-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 IgG4-RD patients. On the other hand, both the EGPA and IgG4-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 IgG4-RD.
Conclusions: The elevation of serum IgG4 as well as pathological IgG4 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.
Keywords: autoimmune diseases; granulomatosis with polyangiitis; inflammation.
© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.