Clinical Practice for IgG4-related Disease and Its Immunological Pathogenesis

Abstract

　Immunoglobulin (Ig) G4-related disease is a chronic inflammatory disorder that can cause irreversible dysfunction in many organs. The eyes, lacrimal glands, extraocular muscles, and optic nerves can be affected. Diagnosis is based on any of the comprehensive diagnostic criteria, criteria for Mikulicz’s disease, and criteria for IgG4-related ophthalmic disease. It is especially important to exclude malignant lymphoma in cases of head and neck lesions. We must evaluate the gene rearrangement of Ig heavy chains. At the time of diagnosis, we must also perform systemic screening of other organ involvements and malignancies. Regarding the pathogenesis, type 2 helper T (Th2) cell inflammation acts on follicular helper T cells to form hyperplastic germinal centers and differentiate into IgG4-bearing plasma cells. Meanwhile, fibroblast proliferation is induced by periostin via interleukin-13, which is produced by Th2 cells. Transforming growth factor-β produced by regulatory T cells and CD4＋cytotoxic T lymphocytes also induces fibrosis. In the future, omics analyses are expected to cause a shift from the current glucocorticoid treatment to molecular-targeted treatments for disease control and prevention of relapse.