The predominant DNA methylation changes were observed in affected tissues of IgG4-RD patients with enriched “MAPK signaling pathway,” “Hippo signaling pathway,” and “VEGF signaling pathway.” Moreover, hypomethylation of IFN-related genes or enriched interferon pathways were not found in peripheral blood or salivary gland tissues of IgG4-RD patients. Here, IFNA1 is linked to immunoglobulin G4-related sclerosing disease.