Biomarkers in autoimmune pancreatitis and immunoglobulin G4-related disease

Abstract

Solitary organ autoimmune disorders, formerly known as autoimmune pancreatitis (AIP), autoimmune sialadenitis, and autoimmune sclerosing cholangitis, are now considered organ-specific manifestations of systemic immunoglobulin G4-related disease (IgG4-RD). AIP and IgG4-RD are characterized by elevated serum concentration of IgG4 antibody (Ab), accumulation of IgG4-expressing plasmacytes in the affected organs, and involvement of multiple organs. It is well established that enhanced IgG4 Ab responses are a hallmark of AIP and IgG4-RD for diagnosis and monitoring disease activity. However, a significant fraction of patients with AIP and IgG4-RD who develop chronic fibroinflammatory responses have normal serum concentrations of this IgG subtype. In addition, disease flare-up is sometimes seen even in the presence of normalized serum concentrations of IgG4 Ab after successful induction of remission by prednisolone. Therefore, it is necessary to identify new biomarkers based on the understanding of the pathophysiology of AIP and IgG4-RD. Recently, we found that activation of plasmacytoid dendritic cells producing both interferon-α (IFN-α) and interleukin-33 (IL-33) mediate murine AIP and human IgG4-RD. More importantly, we provided evidence that serum concentrations of IFN-α and IL-33 could be useful biomarkers for the diagnosis and monitoring of AIP and IgG4-RD activity after induction of remission in these autoimmune disorders. In this Frontier article, we have summarized and discussed biomarkers of AIP and IgG4-RD, including Igs, autoAbs, and cytokines to provide useful information not only for clinicians but also for researchers.

Keywords: Biomarker, Autoimmune pancreatitis, Immunoglobulin G4-related disease, Plasmacytoid dendritic cells, Cytokine, Chemokine

Core Tip: Autoimmune pancreatitis (AIP) and immunoglobulin G4-related disease (IgG4-RD) are new disease entities characterized by enhanced IgG4 antibody responses. Serum concentration of IgG4 antibody is widely used as a useful biomarker for diagnosis and disease activity monitoring in AIP and IgG4-RD. Recent studies have highlighted the importance of cytokine responses in the immunopathogenesis of these disorders. In this Frontier article, we have summarized our knowledge regarding cytokine responses in AIP and IgG4-RD and then discussed the utility of serum concentrations of cytokines as possible biomarkers.