Current status of type 1 (IgG4-related) autoimmune pancreatitis

Abstract

In 1995, Yoshida et al. proposed first the concept of "autoimmune pancreatitis" (AIP). Since then, AIP has been accepted as a new pancreatic inflammatory disease and is now divided two subtypes. Type 1 AIP affected immunoglobulin G4 (IgG4) and implicates the pancreatic manifestation of IgG4-related disease, while type 2 is characterized by neutrophil infiltration and granulocytic epithelial lesions (GEL). Recent research has clarified the clinical and pathophysiological aspects of type 1 AIP, which is more than type 2 among the Japanese population. However, many details remain unclear about the pathogenesis and progression of this disease. In this review, we discuss the current knowledge and recent advances relating to type 1 AIP.

Keywords: Autoimmune pancreatitis; Basophil; IgG4; M2 macrophage; Regulatory T cells.

Fig. 1

Flow chart illustrating the suggested pathophysiology of type 1 autoimmune pancreatitis (AIP). Decreased numbers of circulating naïve regulatory T cells and CD19⁺CD24^highCD27⁺ regulatory B cells (Bregs) may participate in the initiation of type 1 AIP. Interleukin (IL)-35 stimulates the development of eTregs and progression of the disease, and an enhanced Th2 immune response. The production of immunoglobulin (Ig) G4 may be regulated through IL-10 secreted from inducible costimulator (ICOS)-positive Tregs, and basophils and monocytes also control the production of IgG4 via Toll-like receptor signaling. M2 macrophages and tumor growth factor-β secreted from ICOS-negative Tregs may accelerate fibrosis. M2 macrophages may also involve Th2 immune response in type 1 AIP. Neutrophils also affect IgG4 production through neutrophil extracellular traps (NETs)