title: Immunoglobulin class switching to IgG4 in Warthin tumor and analysis of serum IgG4 levels and IgG4-positive plasma cells in the tumor.
abstract: We previously reported a case of immunoglobulin (Ig)G4-related immune inflammation in Warthin tumor. Increased serum IgG4 levels and tissue infiltration of IgG4-positive plasma cells are characteristics of IgG4-related disease (IgG4-RD), a newly emerging clinicopathological entity. However, the relationship between IgG4-RD and Warthin tumor remains to be elucidated. We aimed to investigate the involvement of systemic and local IgG4 production and class-switch recombination in Warthin tumor. We examined serum IgG4 levels and also analyzed the involvement of IgG4-positive plasma cells in Warthin tumors (18 cases) compared with those of pleomorphic adenomas (19 cases) as controls. Furthermore, in specimens of Warthin tumors (3 cases), pleomorphic adenomas (2 cases), and IgG4-RDs (2 cases), we examined messenger RNA expression of activation-induced cytidine deaminase, IgG4 germline transcripts and productive IgG4 by reverse transcription polymerase chain reaction. Serum IgG4 levels were increased in 5 of 18 Warthin tumors and not in any of the 19 pleomorphic adenomas. Infiltration of IgG4-positive plasma cells was detected in 4 Warthin tumors and none in the pleomorphic adenomas. Moreover, activation-induced cytidine deaminase, IgG4 germline transcripts, and productive IgG4 messenger RNA were found to be expressed in 2 of 3 Warthin tumors as well as IgG4-RDs by reverse transcription polymerase chain reaction, but not in pleomorphic adenomas. In conclusion, immunoglobulin class switching to IgG4 may be involved in the pathogenesis of Warthin tumor, and it is possible that certain inflammatory background with an immune reaction is involved in the pathogenesis of Warthin tumor.
authors.affiliation: Division of Otolaryngology, Graduate School of Medicine, Kanazawa University, Kanazawa 920-8641, Japan.
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Aga
authors.affiliation: Division of Otolaryngology, Graduate School of Medicine, Kanazawa University, Kanazawa 920-8641, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kondo
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Kanazawa University Hospital, Kanazawa 920-8641, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Division of Otolaryngology, Graduate School of Medicine, Kanazawa University, Kanazawa 920-8641, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Wakisaka
authors.affiliation: Division of Otolaryngology, Graduate School of Medicine, Kanazawa University, Kanazawa 920-8641, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Yagi-Nakanishi
authors.affiliation: Division of Otolaryngology, Graduate School of Medicine, Kanazawa University, Kanazawa 920-8641, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Tsuji
authors.affiliation: Division of Otolaryngology, Graduate School of Medicine, Kanazawa University, Kanazawa 920-8641, Japan.
authors.forename: Kazuhira
authors.initials: K
authors.lastname: Endo
authors.affiliation: Division of Otolaryngology, Graduate School of Medicine, Kanazawa University, Kanazawa 920-8641, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Murono
authors.affiliation: Division of Otolaryngology, Graduate School of Medicine, Kanazawa University, Kanazawa 920-8641, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Molecular Genetics, Graduate School of Medicine, Kanazawa University, Kanazawa 920-8641, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Muramatsu
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Kanazawa University Hospital, Kanazawa 920-8641, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kawano
authors.affiliation: Division of Otolaryngology, Graduate School of Medicine, Kanazawa University, Kanazawa 920-8641, Japan. Electronic address: tomoy@med.kanazawa-u.ac.jp.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Yoshizaki
mesh_terms: D000235:Adenolymphoma / Q000097:blood / Q000276:immunology* / Q000473:pathology; D000328:Adult; D000368:Aged; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007074:Immunoglobulin G
keywords: Class-switch recombination; IgG4-related disease; Warthin tumor