Up-regulation of activation-induced cytidine deaminase and its strong expression in extra-germinal centres in IgG4-related disease

Yuka Gion, Mai Takeuchi, Rei Shibata, Katsuyoshi Takata, Tomoko Miyata-Takata, Yorihisa Orita, Tomoyasu Tachibana, Tadashi Yoshino, Yasuharu Sato

Research output: Contribution to journalArticle

Abstract

Immunoglobulin (Ig) G4-related disease (IgG4-RD) is a systemic disorder involving benign mass formation due to fibrosis and intense lymphoplasmacytosis; the chronic inflammation associated with the disease might also contribute to oncogenesis. Activation-induced cytidine deaminase (AID), normally expressed in germinal centre activated B-cells, is an enzyme that edits DNA/RNA and induces somatic hypermutation and Ig class switching. AID expression is strictly controlled under physiological conditions; however, chronic inflammation and some infectious agents induce its up-regulation. AID is overexpressed in various cancers and may be important in chronic inflammation-associated oncogenesis. We examined AID expression in IgG4-related sialadenitis (n = 14), sialolithiasis (non-specific inflammation, n = 13), and normal submandibular glands (n = 13) using immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR). Immunohistochemistry revealed significantly more AID-expressing cells in IgG4-related sialadenitis than in sialolithiasis or normal submandibular gland samples (P = 0.02 and P < 0.01, respectively); qPCR yielded similar results. Thus, AID was significantly more up-regulated and had higher expression in extra-germinal centres in IgG4-RD than in non-specific inflammation or normal conditions. This report suggests that IgG4-RD has several specific causes of AID up-regulation in addition to inflammation. Furthermore, chronic inflammation-associated AID-mediated oncogenesis is possible in IgG4-RD.

Original languageEnglish
Article number761
Pages (from-to)761
JournalScientific Reports
Volume9
Issue number1
DOIs
Publication statusPublished - Jan 24 2019

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Germinal Center
Up-Regulation
Immunoglobulin G
Inflammation
Salivary Gland Calculi
Sialadenitis
Carcinogenesis
Submandibular Gland
Real-Time Polymerase Chain Reaction
Immunohistochemistry
Immunoglobulin Class Switching
AICDA (activation-induced cytidine deaminase)
Immunoglobulins
Fibrosis
B-Lymphocytes
RNA
DNA
Enzymes

ASJC Scopus subject areas

  • General

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Up-regulation of activation-induced cytidine deaminase and its strong expression in extra-germinal centres in IgG4-related disease. / Gion, Yuka; Takeuchi, Mai; Shibata, Rei; Takata, Katsuyoshi; Miyata-Takata, Tomoko; Orita, Yorihisa; Tachibana, Tomoyasu; Yoshino, Tadashi; Sato, Yasuharu.

In: Scientific Reports, Vol. 9, No. 1, 761, 24.01.2019, p. 761.

Research output: Contribution to journalArticle

Gion, Yuka ; Takeuchi, Mai ; Shibata, Rei ; Takata, Katsuyoshi ; Miyata-Takata, Tomoko ; Orita, Yorihisa ; Tachibana, Tomoyasu ; Yoshino, Tadashi ; Sato, Yasuharu. / Up-regulation of activation-induced cytidine deaminase and its strong expression in extra-germinal centres in IgG4-related disease. In: Scientific Reports. 2019 ; Vol. 9, No. 1. pp. 761.
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