TY - JOUR
T1 - Up-regulation of activation-induced cytidine deaminase and its strong expression in extra-germinal centres in IgG4-related disease
AU - Gion, Yuka
AU - Takeuchi, Mai
AU - Shibata, Rei
AU - Takata, Katsuyoshi
AU - Miyata-Takata, Tomoko
AU - Orita, Yorihisa
AU - Tachibana, Tomoyasu
AU - Yoshino, Tadashi
AU - Sato, Yasuharu
N1 - Funding Information:
This work was partially supported by a Grant for Intractable Disease (IgG4-related Disease Research Program) from the Ministry of Health, Labor and Welfare in Japan, a Grant-in-Aid for Scientific Research (C) (JSPS KAKENHI Grant Number JP16K08666) and Grant-in-Aid for Young Scientists (B) (JSPS KAKENHI Grant Number 17K17894) from the Japan Society for the Promotion of Science, the Practical Research Project for Rare/ Intractable Diseases from the Japan Agency for Medical Research and Development (AMED), and a donation from the Okayama Medical Foundation.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/1/24
Y1 - 2019/1/24
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-018-37404-x
DO - 10.1038/s41598-018-37404-x
M3 - Article
C2 - 30679751
AN - SCOPUS:85060533607
SN - 2045-2322
VL - 9
SP - 761
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 761
ER -
