Animal models of IgG4-related disease.

Abstract

Immunoglobulin G4-Related Disease (IgG4-RD) is a recently characterized systemic autoimmune disorder marked by multiorgan inflammation and progressive fibrosis. It can affect nearly any organ and may lead to serious clinical consequences. Despite recent progress in developing animal models, therapeutic options for IgG4-RD remain limited, and the pathogenic mechanisms underlying immune dysregulation and fibrosis are still not fully understood. To support mechanistic and therapeutic research, both humanized and non-humanized animal models have been established in recent years. However, the unique biological features of the IgG4 molecule, together with genetic differences between humans and mice, present significant challenges to conventional mouse models. Although several models replicate certain features of IgG4-RD, none fully recapitulate the pathological hallmarks observed in patients. This review critically examines the strengths and limitations of current experimental models and outlines future directions for improving IgG4-RD model systems to better reflect human disease pathogenesis.