Upregulated Expression of Activation-Induced Cytidine Deaminase in Ocular Adnexal Marginal Zone Lymphoma with IgG4-Positive Cells.

Published on Apr 15, 2021in International Journal of Molecular Sciences4.556
· DOI :10.3390/IJMS22084083
Asami Nishikori3
Estimated H-index: 3
Yoshito Nishimura5
Estimated H-index: 5
+ 6 AuthorsYasuharu Sato32
Estimated H-index: 32
Immunoglobulin G4-related disease (IgG4-RD) is a systemic disorder characterized by tissue fibrosis and intense lymphoplasmacytic infiltration, causing progressive organ dysfunction. Activation-induced cytidine deaminase (AID), a deaminase normally expressed in activated B-cells in germinal centers, edits ribonucleotides to induce somatic hypermutation and class switching of immunoglobulin. While AID expression is strictly controlled under physiological conditions, chronic inflammation has been noted to induce its upregulation to propel oncogenesis. We examined AID expression in IgG4-related ophthalmic disease (IgG4-ROD; n = 16), marginal zone lymphoma with IgG4-positive cells (IgG4+ MZL; n = 11), and marginal zone lymphoma without IgG4-positive cells (IgG4- MZL; n = 12) of ocular adnexa using immunohistochemical staining. Immunohistochemistry revealed significantly higher AID-intensity index in IgG4-ROD and IgG4+ MZL than IgG4- MZL (p < 0.001 and = 0.001, respectively). The present results suggest that IgG4-RD has several specific causes of AID up-regulation in addition to inflammation, and AID may be a driver of oncogenesis in IgG4-ROD to IgG4+ MZL.
#1Hisanori UmeharaH-Index: 56
#2Kazuichi Okazaki (Kansai Medical University)H-Index: 85
Last. Mitsuhiro Kawano (Kanazawa University)H-Index: 34
view all 10 authors...
IgG4-related disease (IgG4-RD) is a fascinating clinical entity first reported in this century in Japan, and includes a wide variety of diseases, such as formerly named Mikulicz's disease (MD), autoimmune pancreatitis (AIP), interstitial nephritis, prostatitis and retroperitoneal fibrosis. The Japanese IgG4 team organized by the Ministry of Health, Labor and Welfare (MHLW) of Japan has published the first criteria, comprehensive diagnostic (CD) criteria for IgG-RD 2011. Thereafter, IgG4-RD has b...
2 CitationsSource
#1Hiroyuki Shimizu (TMU: Tokyo Medical University)H-Index: 2
#2Yoshihiko Usui (TMU: Tokyo Medical University)H-Index: 27
Last. Hiroshi Goto (TMU: Tokyo Medical University)H-Index: 28
view all 12 authors...
Purpose To identify tissue metabolomic profiles in biopsy specimens with IgG4-related ophthalmic disease (IgG4-ROD) and mucosa-associated lymphoid tissue (MALT) lymphoma and investigate their potential implication in the disease pathogenesis and biomarkers. Methods We conducted a comprehensive analysis of the metabolomes and lipidomes of biopsy-proven IgG4-ROD (n = 22) and orbital MALT lymphoma (n = 21) specimens and matched adjacent microscopically normal adipose tissues using liquid chromatogr...
1 CitationsSource
#1Jingcheng Zhang (ZJU: Zhejiang University)H-Index: 1
#2Yifen Shi (First Affiliated Hospital of Wenzhou Medical University)H-Index: 1
Last. He Huang (ZJU: Zhejiang University)H-Index: 82
view all 5 authors...
Activation-induced cytidine deaminase (AID) is one kind of the mutant enzymes, which target regulating the immunoglobulin (Ig) gene in Burkitt’s lymphoma to initiate class switch recombination (CSR), resulting in c-Myc chromosomal translocation. However, it is not clear that whether AID induces c-Myc/IgH translocation in double-hit lymphoma (DHL) with c-Myc gene translocation. In this study, the AID in DHL tissues and classical diffuse large b-cell lymphoma (DLBCL) tissues were compared. The res...
2 CitationsSource
#1Yuichi Sumii (Okayama University)H-Index: 2
#2Noboru Asada (Okayama University)H-Index: 15
Last. Yoshinobu Maeda (Okayama University)H-Index: 7
view all 15 authors...
IgG4-producing marginal zone B-cell lymphomas (MZLs) have been recently proposed as a subtype of MZLs. Despite the abundant literature on pathophysiological features of this type of lymphoma, only a few retrospective studies pertaining to the treatment outcomes have been reported, and its prognosis remains unclear. We retrospectively analyzed seven patients with IgG4-producing MZLs diagnosed at our institute, with specific reference to treatment and outcomes. The median age was 69.0 years (55–79...
2 CitationsSource
#1Naoya Nezu (TMU: Tokyo Medical University)H-Index: 4
#2Yoshihiko Usui (TMU: Tokyo Medical University)H-Index: 2
Last. Hiroshi Goto (TMU: Tokyo Medical University)H-Index: 1
view all 12 authors...
The molecular pathogenesis of orbital lymphoproliferative disorders, such as immunoglobulin G4-related ophthalmic disease (IgG4-ROD) and orbital mucosa-associated lymphoid tissue (MALT) lymphoma, remains essentially unknown. Differentiation between the two disorders, which is important since the work-up and treatment can vary greatly, is often challenging due to the lack of specific biomarkers. Although miRNAs play an important role in the regulation of carcinogenesis and inflammation, the relat...
1 CitationsSource
#1Rodolfo Bianchini (Medical University of Vienna)H-Index: 18
#2Sophia N. Karagiannis (Guy's Hospital)H-Index: 32
Last. Erika Jensen-Jarolim (Medical University of Vienna)H-Index: 63
view all 4 authors...
Among the four immunoglobulin G (IgG) subclasses, IgG4 is the least represented in serum of a healthy human and it is considered an “odd” antibody. The IgG4 antibody has unique structural features that affect its biological function. These include the ability to undergo antigen-binding fragment (Fab)-arm exchange, to create fragment crystallizable (Fc) – Fc binding with other IgG4 and other IgG subclass antibodies, have a unique affinity profile for Fc gamma receptors (FcγRs) and no binding to c...
9 CitationsSource
#1Kai-Ming Li (Sichuan University)H-Index: 1
#2Man-Hua XuH-Index: 1
Last. Wei-Min He (Sichuan University)H-Index: 1
view all 4 authors...
Objective This study aims to study the expression and role of IgG and IgG4 in orbital MALT lymphoma and to compare the characteristics of IgG4-related diseases. Patients and Methods Patients with orbital MALT lymphoma, treated in the West China Hospital of Sichuan University from 2012 to 2017, were enrolled in the current study. The immunological examination of the wax blocks of orbital masses was performed again and the expression level of IgG and IgG4 in pathological tissue was analyzed. Resul...
1 CitationsSource
#1Ko Harada (Okayama University)H-Index: 3
#2Fumio Otsuka (Okayama University)H-Index: 35
1 CitationsSource
#1Emanuele Zucca (University of Bern)H-Index: 83
#2Luca Arcaini (UNIPV: University of Pavia)H-Index: 65
Last. M. LadettoH-Index: 13
view all 12 authors...
27 CitationsSource
#1Yuka Kawaji (Kyoto Prefectural University of Medicine)H-Index: 3
#2Hiroaki NagataH-Index: 2
Last. Junya Kuroda (Kyoto Prefectural University of Medicine)H-Index: 41
view all 11 authors...
3 CitationsSource
Cited By0