IgG4-related disease: Changing epidemiology and new thoughts on a multisystem disease

Abstract

IgG4-related disease (IgG4-RD) represents an immune-mediated fibroinflammatory condition with peculiar histopathologic changes that can affect various organs. In 2012 its unified nomenclature was published, which allows to abandon other synonymous names. Up to now, only little is known about its epidemiology around the world. However, although it is generally considered a rare condition, the number of patients with IgG4-RD is increasing enormously. Likewise, the annual number of publications on this subject has increased progressively. The spectrum of clinical manifestations in IgG4-RD is highly variable, depending on the severity of the disease as well as the presence of organ(s) involvement. This review gives an overview on changing epidemiology of IgG4-RD focusing the attention on the large cohorts of patients published in the literature.

Keywords: Epidemiology; Genetic factors; IgG4; IgG4-related disease.

Fig. 1

Pathogenic mechanisms of IgG4-RD: a) Eventual initial mechanisms include local autoantigens, infectious agents, allergic components in a genetically predisposed individual; b) These factors activate immune reaction in the target tissue (organ/organs) which is characterized by Th2 predominance with an increased production of cytokines (IL-4, IL-5, IL-13) and tumour growth factor -b (TGF-b). Moreover, an activation of Treg, a release of IL-10 and elevated serum IgE occur. The immune reaction also causes a B cell class switching with an increased production of IgG4 producing plasma cells. APC = antigen presenting cell; Tc = cytotoxic T lymphocyte; Treg = regulatory T cell.