Autoimmune pancreatitis--a new evolving pancreatic disease?

Area of Science:

• Immunology
• Gastroenterology
• Pathology

Background:

• Autoimmune pancreatitis (AIP) is increasingly recognized as a systemic disease, evidenced by extrapancreatic lesions sharing pathological features with pancreatic lesions.
• These shared features include fibrosis, abundant IgG4-positive plasma cell infiltration, and responsiveness to steroid therapy, leading to proposed diagnostic criteria.
• Despite global acceptance as a distinct clinical entity, the precise pathogenetic mechanisms underlying AIP remain incompletely understood.

Purpose of the Study:

• To elucidate the pathogenetic mechanisms of autoimmune pancreatitis (AIP).
• To review and synthesize current knowledge on genetic, humoral, and cellular immunity aspects of AIP.
• To propose a biphasic model for AIP pathogenesis involving induction and progression phases.

Main Methods:

• Comprehensive review of existing literature on genetic background, humoral immunity, target antigens (self-antigens and microbial mimicry), cellular immunity (including regulatory T cells), complement system activation, and experimental models.
• Analysis of findings to formulate a hypothesis for AIP pathogenesis.
• Examination of the roles of regulatory T cells (Tregs) and immune responses in both disease induction and progression.

Main Results:

• A biphasic pathogenetic mechanism for AIP, termed "induction" and "progression," is proposed.
• The induction phase involves an initial response to self-antigens or molecular mimicry (e.g., Helicobacter pylori), triggered by decreased naive regulatory T cells (Tregs).
• This early phase is characterized by Th1 cell-mediated release of pro-inflammatory cytokines (IFN-γ, IL-1b, IL-2, TNF-α).

Conclusions:

• The progression phase in chronic AIP is characterized by increased memory Tregs and Th2 immune responses.
• Activation of the classical complement pathway may occur via IgG1 immune complexes.
• Regulatory T cells (Tregs) play critical roles in both the induction and progression of autoimmune pancreatitis, necessitating further research into their precise functions.