Identification of serum IFN-α and IL-33 as novel biomarkers for type 1 autoimmune pancreatitis and IgG4-related disease

Abstract

IgG4-related disease (IgG4-RD) is a multi-organ autoimmune disease characterized by elevated serum IgG4 concentration. Although serum IgG4 concentration is widely used as a biomarker for IgG4-RD and type 1 autoimmune pancreatitis (AIP), a pancreatic manifestation of IgG4-RD, a significant number of patients have normal serum IgG4 levels, even in the active phase of the disease. Recently, we reported that the development of experimental AIP and human type 1 AIP is associated with increased expression of IFN-α and IL-33 in the pancreas. In this study, we assessed the utility of serum IFN-α and IL-33 levels as biomarkers for type 1 AIP and IgG4-RD. Serum IFN-α and IL-33 concentrations in patients who met the diagnostic criteria for definite type 1 AIP and/or IgG4-RD were significantly higher than in those with chronic pancreatitis or in healthy controls. Strong correlations between serum IFN-α, IL-33, and IgG4 concentrations were observed. Diagnostic performance of serum IFN-α and IL-33 concentrations as markers of type 1 AIP and/or IgG4-RD was comparable to that of serum IgG4 concentration, as calculated by the receiver operating characteristic curve analysis. Induction of remission by prednisolone treatment markedly decreased the serum concentration of these cytokines. We conclude that serum IFN-α and IL-33 concentrations can be useful as biomarkers for type 1 AIP and IgG4-RD.

Intestinal Dysbiosis and Autoimmune Pancreatitis

“…Taken together, these results strongly suggest that activation of pDCs and robust production of IFN-a and IL-33 are prominent features of murine experimental and human AIP. This idea has been fully supported by recent identification of serum IFN-a and IL-33 as novel biomarkers for human AIP and IgG4-RD (35). Although recognition of MAMPs by TLR7 or TLR9 in pDCs induces IFN-a production (31,32), the involvement of these TLRs in pDCs needs to be determined ( Figure 1).…”

Review of Diagnostic Biomarkers in Autoimmune Pancreatitis: Where Are We Now?

“…Minaga et al reported that IFN-α and IL-33 may serve as biomarkers for AIP and IgG4-RD [ 26 ]. They previously reported that IFN-α and IL-33 produced by plasmacytoid dendritic cells (pDCs) mediate chronic fibro-inflammation in both experimental AIP and human type 1 AIP [ 47 ].…”

“…The usefulness of IFN-α and IL-33 as biomarkers for AIP/IgG4 was evaluated in 21 patients with AIP/IgG4, 12 patients with chronic pancreatitis, and 8 healthy subjects. The sensitivity of IFN-α and IL-33 were 85.7% each, and their specificities were 91.7% and 83.3%, respectively [ 26 ]. Both IFN and IL-33 exhibited a strong correlation with IgG4 [ 26 ].…”

“…The sensitivity of IFN-α and IL-33 were 85.7% each, and their specificities were 91.7% and 83.3%, respectively [ 26 ]. Both IFN and IL-33 exhibited a strong correlation with IgG4 [ 26 ]. However, this study was a single-center retrospective study; a large multicenter study is needed to verify their findings.…”

“…The presence of diffuse pancreatic swelling and IAC-complicated AIP are considered clinical predictors of AIP relapse; however, objective evaluation using biomarkers is desirable [ 13 ]. Serum levels of some candidate biomarkers decline following steroid treatment, suggesting their use in monitoring steroid treatment [ 15 , 20 , 21 , 26 ]. However, there are few biomarkers associated with the prediction of AIP relapse.…”