Pathogenesis exploration of lgG4-related disease: From the traditional central dogma and its remodeling perspective

Immunoglobulin G4-related disease (IgG4-RD) is a chronic disease characterized by inflammation and fibrosis within multiple organs. The fundamental immunopathogenic mechanisms of IgG4-RD remain largely unidentified. Advancements in multiple omics technologies have enabled researchers to characterize the cellular heterogeneity of IgG4-RD. The pursuit of understanding the immune dysfunction in IgG4-RD is principally guided by genomic, transcriptomic, and proteomic investigations, encompassing three crucial aspects of the traditional central dogma. Besides, genetic and epigenetic mechanisms, along with alterations in posttranslational modifications (PTMs) and small molecules identified through metabolomics and microbiomics studies, interact to uncover the functional basis of abnormal cellular activities. Here, we systematically review the application of multiple omics technologies to uncover the fundamental mechanisms driving IgG4-RD, organized around the traditional central dogma of molecular biology and its remodeling. We also propose an integrated pathophysiological model of multi-layered immune dysregulation, illustrating a self-sustaining loop of immune activation and tissue remodeling in IgG4-RD. It is believed that adopting a combination of diverse technological advancements to examine a series of cellular processes holds promise for the development of personalized approaches to managing IgG4-RD patients.