Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 21, 2021; 27(19): 2257-2269
Published online May 21, 2021. doi: 10.3748/wjg.v27.i19.2257
Biomarkers in autoimmune pancreatitis and immunoglobulin G4-related disease
Akane Hara, Tomohiro Watanabe, Kosuke Minaga, Tomoe Yoshikawa, Ken Kamata, Masatoshi Kudo
Akane Hara, Tomohiro Watanabe, Kosuke Minaga, Tomoe Yoshikawa, Ken Kamata, Masatoshi Kudo, Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama 589-8511, Japan
Author contributions: Hara A, Watanabe T, and Minaga K drafted the manuscript; Yoshikawa T, Kamata K, and Kudo M edited and revised the manuscript; Hara A, Watanabe T, Minaga K, Yoshikawa T, Kamata K and Kudo M have read and approved the final manuscript; all authors therefore meet the criteria for authorship established by the International Committee of Medical Journal Editors.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Tomohiro Watanabe, MD, PhD, Associate Professor, Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama 589-8511, Japan.
Received: February 11, 2021
Peer-review started: February 11, 2021
First decision: March 14, 2021
Revised: March 19, 2021
Accepted: April 26, 2021
Article in press: April 26, 2021
Published online: May 21, 2021

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.